Multiple MyelomaPhase 1NCT03828292
An Open-label, Dose Escalation Study in Japanese Participants With Relapsed/Refractory Multiple Myeloma Who Have Failed Prior Anti Myeloma Treatments
A Phase 1 study testing Belantamab mafodotin, Bortezomib and Dexamethasone in people with Multiple Myeloma, run by GlaxoSmithKline at 4 sites in Japan.
Trial summary
Belantamab mafodotin (GSK2857916) is a first in class, antibody dependent cellular cytotoxicity (ADCC) enhanced, humanized immunoglobulin G1 (IgG1) antibody-drug conjugate (ADC) which binds specifically to B cell maturation antigen (BCMA) expressed on tumor cells of all participants with multiple myeloma. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Belantamab mafodotin, Bortezomib and Dexamethasone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 4 sitesJapan
- Study dates
- 14 Mar 2019to 5 Sep 2024
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provide signed written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- Male or female, 20 years or older (at the time consent is obtained).
- ECOG performance status of 0 to 2.
- Histologically or cytologically confirmed diagnosis of multiple myeloma as defined according to IMWG 2014, criteria in a participant who fulfills all of the following: has undergone stem cell transplant, or is considered transplant ineligible, Part 1: has received at least 2 prior lines of anti-myeloma drugs containing at least 1 proteasome inhibitor and at least 1 immunomodulator, Part 2: has received at least 1 prior line of anti-myeloma drugs; has demonstrated progression on, or within 60 days of completion of the last therapy.
- Has measurable disease with at least one of the following: serum M-protein >=0.5 grams per deciliter (g/dL) (>=5 grams per liter [g/L]); Urine M-protein >=200 mg/24 hours; Serum free light chain (FLC) assay: Involved FLC level >=10 mg/dL (>=100 mg/L) and an abnormal serum FLC ratio (<0.26 or >1.65).
- Participants with a history of autologous stem cell transplant are eligible for study participation provided the following eligibility criteria are met: Transplant was >100 days prior to study enrolment; No active infection.
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- Female participants: Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. A female participant is eligible to participate if she is not pregnant or breast feeding, and at least one of the following conditions applies: Is not a woman of childbearing potential (WOCBP) or For Part 1 and Part 2 Arm A: Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1 percent per year), preferably with low user dependency, during the treatment period and for 4 months after the last dose of GSK2857916, and 7 months from the last dose of bortezomib (only Part 2 Arm A), and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study treatment. A WOCBP must have a negative highly sensitive serum pregnancy test (as required by local regulations) within 72 hours before the first dose of study treatment and agree to use effective contraception during the study and for 4 months after the last dose of GSK2857916, and 7 months from the last dose of bortezomib (only Part 2 Arm A); For Part 2 Arm B: Due to pomalidomide being a thalidomide analogue with risk for embryo-fetal toxicity and prescribed under a restricted distribution program, WOCBP participants will be eligible if they commit either to abstain continuously from heterosexual sexual intercourse or to use 2 methods of reliable birth control, beginning 4 weeks prior to initiating treatment with pomalidomide, during therapy, during dose interruptions and continuing for 4 weeks following discontinuation of pomalidomide treatment. Thereafter, WOCBP participants must use a contraceptive method that is highly effective (with a failure rate of <1 percent per year) for a further 3 months, and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. Two negative pregnancy tests must be obtained prior to initiating pomalidomide therapy. The first test should be performed within 10 to 14 days and the second test within 24 hours prior to prescribing pomalidomide therapy. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
- Male participants: Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Male participants are eligible to participate if they agree to the following from the time of first dose of study treatment until 6 months after the last dose of GSK2857916, 4 months after the last dose of bortezomib (only Part 2 Arm A), and 4 weeks after the last dose of pomalidomide (only Part 2 Arm B) to allow for clearance of any altered sperm: Refrain from donating sperm plus either: Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent; or must agree to use contraception/barrier as detailed: Agree to use a male condom even if they have undergone a successful vasectomy and female partner to use an additional highly effective contraceptive method with a failure rate of <1 percent per year as when having sexual intercourse with a woman of childbearing potential (including pregnant females).
- All prior treatment-related toxicities (defined by National Cancer Institute-Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 4.03, must be <=Grade 1 at the time of enrolment except for alopecia. Participants with Grade 2 peripheral neuropathy can be enrolled into Part 1 and Part 2 Arm B but not into Part 2 Arm A.
- Adequate Organ System Function. Exclusion Criteria
- Systemic anti-tumor-therapy within 14 days, or plasmapheresis within 7 days prior to the first dose of study treatment.
- Symptomatic amyloidosis, active 'polyneuropathy, organomegaly, endocrinopathy, myeloma protein, and skin changes' (POEMS) syndrome, active plasma cell leukemia at the time of screening.
- Use of an investigational drug within 14 days or 5 half-lives, whichever is shorter, preceding the first dose of study treatment. Prior treatment with a monoclonal antibody within 30 days of receiving the first dose of study treatment. Prior BCMA targeted therapy.
- History of an allogeneic stem cell transplant.
- Current use of prohibited medications/device or planned use of any of these during the study period.
- Current corneal epithelial disease except mild punctate keratopathy
- Presence of active renal condition (infection, requirement for dialysis or any other condition that could affect participant's safety). Participants with isolated proteinuria resulting from multiple myeloma are eligible, provided they fulfil the required criteria.
- Evidence of active mucosal or internal bleeding.
- Any major surgery within the last 4 weeks.
- Any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions (including laboratory abnormalities) that could interfere with participant's safety, obtaining informed consent or compliance to the study procedures.
- Active infection requiring treatment (antibiotic, antiviral, or antifungal treatment).
- Evidence of severe or uncontrolled systemic diseases.
- Malignancies other than disease under study are excluded, except for any other malignancy from which the participant has been disease-free for more than 2 years and, in the opinion of the investigators and Medical Monitor, will not affect the evaluation of the effects of this clinical study treatment on the currently targeted malignancy (multiple myeloma).
- Evidence of cardiovascular risk including any of the following:
- Corrected QT interval Fridericia (QTcF) interval >=470 milliseconds (msecs) (the QT interval values must be corrected for heart rate by Fridericia's formula [QTcF])
- Evidence of current clinically significant uncontrolled arrhythmias, including clinically significant ECG abnormalities such as 2nd degree (Type II) or 3rd degree atrioventricular (AV) block.
- History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within 6 months of Screening.
- Class III or IV heart failure as defined by the New York Heart Association functional classification system
- Uncontrolled hypertension
- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to GSK2857916 or any of the components of the study treatment.
- Pregnant or lactating female or female who are interrupting lactation.
- Known human Immunodeficiency virus (HIV) infection.
- Presence of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb) or hepatitis B core antibody (HBcAb at Screening or within 3 months prior to first dose of study treatment).
- Positive hepatitis C antibody test result or positive hepatitis C ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study treatment. Participants with positive hepatitis C antibody due to prior resolved disease can only be enrolled, if a confirmatory negative hepatitis C RNA test is obtained. Hepatitis RNA testing is optional and participants with negative hepatitis C antibody test are not required to also undergo hepatitis C RNA testing.
- Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. Stable chronic liver disease (including Gilbert's syndrome or asymptomatic gallstones) or hepatobiliary involvement of malignancy is acceptable if participant otherwise meets entry criteria.
- Previously diagnosed with interstitial lung disease or current complication of interstitial lung disease.
- Additional Exclusion Criteria for Part 2 Arm A
- Intolerant to bortezomib or refractory to bortezomib.
- Ongoing Grade 2 or higher peripheral neuropathy or neuropathic pain.
- Intolerance or contraindications to herpes zoster prophylaxis Additional Exclusion Criteria for Part 2 Arm B
- Prior pomalidomide use.
- Intolerance or contraindications to antithrombotic prophylaxis.
- Active or history of venous thromboembolism within 3 months prior to first dose of study treatment.
Who cannot join
None listed.
Trial locations and contacts
4 sites in 1 country.
Japan4 sites
GSK Investigational Site
Aichi, 467-8602
GSK Investigational Site
Okayama, 701-1192
GSK Investigational Site
Shibuya-Ku, Tokyo, 150-8935
GSK Investigational Site
Tokyo, 135-8550
About this study
Official title: A Phase I Open-Label, Dose Escalation Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Clinical Activity of the Antibody Drug Conjugate GSK2857916 in Japanese Participants With Relapsed/Refractory Multiple Myeloma
Belantamab mafodotin (GSK2857916) is a first in class, antibody dependent cellular cytotoxicity (ADCC) enhanced, humanized immunoglobulin G1 (IgG1) antibody-drug conjugate (ADC) which binds specifically to B cell maturation antigen (BCMA) expressed on tumor cells of all participants with multiple myeloma. This is a Phase 1, open label, dose escalation study to investigate safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity and clinical activity of GSK2857916 when given as monotherapy (Part 1) or given as combination therapy (Part 2). Dose escalation will follow a 3+3 design.
- Conditions
- Multiple Myeloma
- Being tested
- Belantamab mafodotin, Bortezomib, Dexamethasone, Pomalidomide
- Keywords
- Antibody drug conjugate, Dose-escalation, GSK2857916, Japanese, Relapsed/Refractory Multiple Myeloma
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Belantamab mafodotinDrug
Belantamab mafodotin will be administered as an intravenous infusion.
BortezomibDrug
Bortezomib solution for injection will be administered subcutaneously.
DexamethasoneDrug
Dexamethasone tablets will be administered orally.
PomalidomideDrug
Pomalidomide capsules will be administered orally.
| Study group | Role | What they receive |
|---|---|---|
| Part 1: Belantamab mafodotin Monotherapy | Experimental | Not described Receives: Drug: Belantamab mafodotin |
| Part 2: Arm A: Belantamab mafodotin+Bortezomib/Dexamethasone | Experimental | Not described Receives: Drug: Belantamab mafodotin; Drug: Bortezomib; Drug: Dexamethasone |
| Part 2: Arm B: Belantamab mafodotin+Pomalidomide/Dexamethasone | Experimental | Not described Receives: Drug: Belantamab mafodotin; Drug: Dexamethasone; Drug: Pomalidomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)
DLT is an Adverse Event (AE) that is considered by the investigator to be clinically relevant and attributed to the study therapy during the 21-day DLT period and meets at least one of the DLT criteria: Grade 3 or greater febrile neutropenia lasting >48 hours (h) despite adequate treatment, Grade 4 thrombocytopenia <25,000/mm^3accompanied by clinically significant bleeding, any Grade 3 or greater non-hematologic toxicity, any Grade 3 or greater non-hematologic laboratory value if: laboratory abnormality persists for >48 h despite supportive treatment for abnormality leads to hospitalization, Grade 4 Corneal toxicity, and liver toxicity meeting pre-specified GlaxoSmithKline liver stopping criteria. DLTs were assessed by National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 4.03.
Measured: Up to Day 21
Part 2: Arm A: Number of Participants With DLTs
DLT is an AE that is considered by the investigator to be clinically relevant and attributed to the study therapy during the 21-day DLT period and meets at least one of the DLT criteria: Grade 3 or greater febrile neutropenia lasting >48 hours (h) despite adequate treatment, Grade 4 thrombocytopenia <25,000/mm^3 accompanied by clinically significant bleeding, any Grade 3 or greater non-hematologic toxicity, any Grade 3 or greater non-hematologic laboratory value if: laboratory abnormality persists for >48 h despite supportive treatment or abnormality leads to hospitalization, Grade 4 Corneal toxicity, and liver toxicity meeting pre-specified GlaxoSmithKline liver stopping criteria. DLTs were assessed by NCI-CTCAE, version 4.03.
Measured: Up to Day 21
Part 2: Arm B: Number of Participants With DLTs
DLT is an AE that is considered by the investigator to be clinically relevant and attributed to the study therapy during the 21-day DLT period and meets at least one of the DLT criteria: Grade 3 or greater febrile neutropenia lasting >48 hours (h) despite adequate treatment, Grade 4 thrombocytopenia <25,000/mm^3 accompanied by clinically significant bleeding, any Grade 3 or greater non-hematologic toxicity, any Grade 3 or greater non-hematologic laboratory value if: laboratory abnormality persists for >48 h despite supportive treatment or abnormality leads to hospitalization, Grade 4 Corneal toxicity, and liver toxicity meeting pre-specified GlaxoSmithKline liver stopping criteria. DLTs were assessed by NCI-CTCAE, version 4.03.
Measured: Up to Day 28
Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death; was life threatening; required hospitalization or prolongation of existing hospitalization; resulted in disability/incapacity; was a congenital anomaly/birth defect. SAEs are subset of AEs.
Measured: Up to approximately 141 weeks
Part 2: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose results in death, Is life-threatening, Requires inpatient hospitalization or prolongation of existing hospitalization, Results in persistent disability/incapacity or Is a congenital anomaly/birth defect other situations which involve medical or scientific judgment or is associated with liver injury and impaired liver function. SAEs are subset of AEs.
Measured: Up to approximately 212 weeks
Part 1: Number of Participants With Worst-case Grade Change From Baseline in Clinical Chemistry Parameters
Blood samples were collected for clinical chemistry parameters analysis: Creatine Kinase (CK), Creatinine, Gamma Glutamyl Transferase (GGT), Magnesium, Phosphate, Potassium, Sodium, Calcium, Glucose, Urate, Alanine Aminotransferase (ALT), Albumin, Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Bilirubin were graded according to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version (v) 4.03. Grade (G)1: mild; G2: moderate; G3: severe or medically significant; G4: life-threatening consequences. Higher grade indicates greater severity and increase in grade was defined relative to Baseline grade. Any worst-case post baseline increases in grade along with any increase to a maximum G3 and a maximum G4 are presented. Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.
Measured: Baseline (Day 1) and up to approximately 141 weeks
Part 1: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters
Blood samples were collected for analysis of clinical chemistry parameters: C Reactive Protein, Chloride, Direct Bilirubin (DB), Lactate Dehydrogenase, Protein and Urea. The summaries of worst-case change from baseline with respect to normal range was analyzed for only those laboratory tests that were not gradable by CTCAE v4.03. The number of participants with decreases to low from baseline, changes to normal or no changes from baseline, and increases to high values have been presented. Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.
Measured: Baseline (Day 1) and up to approximately 141 weeks
Part 2: Number of Participants With Worst-case Grade Change From Baseline in Clinical Chemistry Parameters
Blood samples were collected for clinical chemistry parameters analysis: Creatine Kinase (CK), Creatinine, Gamma Glutamyl Transferase (GGT), Magnesium, Phosphate, Potassium, Sodium, Calcium, Glucose, Urate, Alanine Aminotransferase (ALT), Albumin, Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Bilirubin were graded according to NCI-CTCAE v 4.03. G1: mild; G2: moderate; G3: severe or medically significant; G4: life-threatening consequences. Higher grade indicates greater severity and increase in grade was defined relative to Baseline grade. Any worst-case post baseline increases in grade along with any increase to a maximum G3 and a maximum G4 are presented. Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.
Measured: Baseline (Day 1) and up to approximately 212 weeks
Part 2: Number of Participants With Worst-case Change Post-baseline in Clinical Chemistry Parameters
Blood samples were collected for analysis of clinical chemistry parameters: C Reactive Protein, Chloride, Direct Bilirubin (DB), Lactate Dehydrogenase, Protein and Urea. The summaries of worst-case change from baseline with respect to normal range was analyzed for only those laboratory tests that were not gradable by CTCAE v4.03. The number of participants with decreases to low from baseline, changes to normal or no changes from baseline, and increases to high values have been presented. Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.
Measured: Baseline (Day 1) and up to approximately 212 weeks
Part 1: Number of Participants With Worst-case Grade Change From Baseline in Hematology Parameters
Blood samples were collected for analysis of hematology parameters: Hemoglobin, Leukocytes, Lymphocytes, Neutrophils and Platelets were graded according to CTCAE v4.03. G1: mild; G2: moderate; G3: severe or medically significant; G4: life-threatening consequences. Higher grade indicates greater severity and increase in grade was defined relative to Baseline grade. Any worst-case post baseline increases in grade along with any increase to a maximum G3 and a maximum G4 are presented. Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.
Measured: Baseline (Day 1) and up to approximately 141 weeks
Part 1: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters
Blood samples were collected for the analysis of following hematology parameters: Basophils, Eosinophils, Mean Corpuscular Hemoglobin Concentration (MCHC), Mean Corpuscular Hemoglobin (MCH), Mean Corpuscular Volume (MCV), erythrocytes, Hematocrit, monocytes and reticulocytes. The summaries of worst-case change from baseline with respect to normal range was analyzed for only those laboratory tests that were not gradable by CTCAE version 4.03. The number of participants with decreases to low from baseline, changes to normal or no changes from baseline, and increases to high values have been presented. Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.
Measured: Baseline (Day 1) and up to approximately 141 weeks
Part 2: Number of Participants With Worst-case Grade Change From Baseline in Hematology Parameters
Blood samples were collected for analysis of hematology parameters: Hemoglobin, Leukocytes, Lymphocytes, Neutrophils and Platelets were graded according to CTCAE v4.03. G1: mild; G2: moderate; G3: severe or medically significant; G4: life-threatening consequences. Higher grade indicates greater severity and increase in grade was defined relative to Baseline grade. Any worst-case post baseline increases in grade along with any increase to a maximum G3 and a maximum G4 are presented. Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.
Measured: Baseline (Day 1) and up to approximately 212 weeks
Part 2: Number of Participants With Worst-case Change Post-baseline in Hematology Parameters
Blood samples were collected for the analysis of following hematology parameters: Basophils, Eosinophils, MCHC, MCH, MCV, erythrocytes, Hematocrit, monocytes and reticulocytes. The summaries of worst-case change from baseline with respect to normal range was analyzed for only those laboratory tests that were not gradable by CTCAE version 4.03. The number of participants with decreases to low, changes to normal or no changes, and increases to high from baseline values have been presented. Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.
Measured: Baseline (Day 1) and up to approximately 212 weeks
Part 1: Number of Participants With Worst-case Change in Post Baseline Values Relative to Baseline Urinalysis Results: Occult Blood and Protein
Urine samples were collected to analyze presence of occult blood and protein in urine by dipstick method. Data for worst-case post baseline urinalysis results is presented. Result for urinalysis parameters were recorded as no change/decreased, Increase to SMALL, Increase to MODERATE, Increase to LARGE, and any increase including increase to +-, 1+, 2+, 3+, unknown indicating proportional concentrations in the urine sample.
Measured: Baseline (Day 1) and up to approximately 141 weeks
Part 2: Number of Participants With Worst-case Change in Post Baseline Values Relative to Baseline Urinalysis Results: Occult Blood and Protein
Urine samples were collected to analyze presence of occult blood and protein in urine by dipstick method. Data for worst-case post baseline urinalysis results is presented. Result for urinalysis parameters were recorded as no change/decreased, Increase to SMALL, Increase to MODERATE, Increase to LARGE, and any increase including increase to +-, 1+, 2+, 3+, unknown indicating proportional concentrations in the urine sample.
Measured: Baseline (Day 1) and up to approximately 212 weeks
Part 1: Change From Baseline (CFB) in Urine Potential of Hydrogen (pH)
Urine samples were collected to analyze urine pH levels. Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.
Measured: Baseline (Day 1) and up to approximately 141 weeks
Part 2: Change From Baseline in Urine Potential of Hydrogen (pH)
Urine samples were collected to analyze urine pH levels. Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.
Measured: Baseline (Day 1) and up to approximately 212 weeks
Part 1: Change From Baseline in Urine Specific Gravity by Dipstick
Urine samples were collected to analyze urine specific gravity. Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.
Measured: Baseline (Day 1) and up to approximately 141 weeks
Part 2: Change From Baseline in Urine Specific Gravity by Dipstick
Urine samples were collected to analyze urine specific gravity. Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.
Measured: Baseline (Day 1) and up to approximately 212 weeks
Part 1: Number of Participants With Worst-case Grade Change Post-baseline in Vital Sign Parameters: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
DBP and SBP were measured after resting for at least 5 minutes in a supine or semi-recumbent position. They were graded according to NCI-CTCAE version 4.03. For SBP: Grade (G) 0 (<120 millimeter of mercury [mmHg]), G1 (120-139 mmHg), G2 (140-159 mmHg), G3 (>=160 mmHg). For DBP: G0 (<80 mmHg), G1 (80-89 mmHg), G2 (90-99 mmHg), G3 (>=100 mmHg). Higher grade indicates greater severity. Data for participants with worst-case post baseline with any grade increase and a maximum post-baseline grade increase to G2 and G3 from their baseline grade are presented. Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.
Measured: Baseline (Day 1) and up to approximately 141 weeks
Part 2: Number of Participants With Worst-case Grade Change Post-baseline in Vital Sign Parameters: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
DBP and SBP were measured after resting for at least 5 minutes in a supine or semi-recumbent position. They were graded according to NCI-CTCAE version 4.03. For SBP: Grade (G) 0 (<120 millimeter of mercury [mmHg]), G1 (120-139 mmHg), G2 (140-159 mmHg), G3 (>=160 mmHg). For DBP: G0 (<80 mmHg), G1 (80-89 mmHg), G2 (90-99 mmHg), G3 (>=100 mmHg). Higher grade indicates greater severity. Data for participants with worst-case post baseline with any grade increase and a maximum post-baseline grade increase to G2 and G3 from their baseline grade are presented. Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.
Measured: Baseline (Day 1) and up to approximately 212 weeks
Part 1: Number of Participants With Worst-case Change Post-baseline in Vital Sign Parameters: Temperature
Temperature was measured after resting for at least 5 minutes. The abnormal ranges for body temperature were (<=35 degrees Celsius or >=38 degrees Celsius). Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.
Measured: Baseline (Day 1) and up to approximately 141 weeks
Part 2: Number of Participants With Worst-case Change Post-baseline in Vital Sign Parameters: Temperature
Temperature was measured after resting for at least 5 minutes. The abnormal ranges for body temperature were (<=35 degrees Celsius or >=38 degrees Celsius). Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.
Measured: Baseline (Day 1) and up to approximately 212 weeks
Part 1: Number of Participants With Worst-case Change Post-baseline in Vital Sign Parameters: Heart Rate
Heart rate was measured after resting for at least 5 minutes. The abnormal ranges for heart rate were (low <60 beats per minute [bpm] and high >100 bpm). Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits. Data for participants with worst case change from baseline was presented as Baseline to low, Baseline to Normal or No change and Baseline to High.
Measured: Baseline (Day 1) and up to approximately 141 weeks
Part 2: Number of Participants With Worst-case Change Post-baseline in Vital Sign Parameters: Heart Rate
Heart rate was measured after resting for at least 5 minutes. The abnormal ranges for heart rate were (low <60 beats per minute [bpm] and high >100 bpm). Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits. Data for participants with worst case change from baseline was presented as Baseline to low, Baseline to Normal or No change and Baseline to High.
Measured: Baseline (Day 1) and up to approximately 212 weeks
Part 1: Number of Participants With Worst-Case Amount of Increase From Baseline Value in Corrected QT Interval Using Fredericia's Formula (QTcF)
12-lead electrocardiogram (ECG) was obtained using an automated ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and QT interval corrected using Fridericia's formula (QTcF) intervals. Grade 0 (<450 millisecond (msec)), Grade 1 (450-480 msec), Grade 2 (481-500 msec), and Grade 3 (≥501 msec). Higher grade indicates greater severity. Data for participants with worst-case post baseline with any grade increase and a post-baseline grade increase to G2 and G3 from their baseline grade are presented. Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.
Measured: Baseline (Day 1) and up to approximately 141 weeks
Part 2: Number of Participants With Worst-Case Amount of Increase From Baseline Value in QTcF
12-lead electrocardiogram (ECG) was obtained using an automated ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and QT interval corrected using Fridericia's formula (QTcF) intervals. Grade 0 (<450 millisecond (msec)), Grade 1 (450-480 msec), Grade 2 (481-500 msec), and Grade 3 (≥501 msec). Higher grade indicates greater severity. Data for participants with worst-case post baseline with any grade increase and a post-baseline grade increase to G2 and G3 from their baseline grade are presented. Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.
Measured: Baseline (Day 1) and up to approximately 212 weeks
Part 1: Number of Participants With Worst-case Change Post-baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status
The number of participants with worst-case post baseline performance status have been presented as 0-5. Where, 0- Fully active; 1- Restricted in strenuous activity but able to carry out light work activities; 2- Capable of self-care but unable to carry out any work activities; 3- Capable of limited self care, confined to bed/chair more than 50% of waking hours; 4- Completely disabled; can't carry on any self care; totally confined to bed/chair and 5- Dead.Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.
Measured: Baseline (Day 1) and up to approximately 141 weeks
Part 2: Number of Participants With Clinically Significant Abnormalities in ECOG Performance Status
Any change in ECOG Performance status that was clinically significant in the medical and scientific judgment of the investigator and not related to an underlying disease was reported.
Measured: Baseline (Day 1) and up to approximately 212 weeks
Secondary outcomes (78)
Part 1: Area Under the Concentration-time Curve During the Dosing Interval (AUC (0-tau)) Following Single Dose Administration of Belantamab Mafodotin (Antibody-drug Conjugate (ADC))
Blood samples were collected for pharmacokinetic (PK) analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Pre-Dose; End of Infusion (EOI); 1 hour (h), 3 h, 8 h and 24 h post-EOI, Day 8, Day 15 in Cycle 1; Pre-Dose on Cycle 2 Day 1
Part 1: AUC Extrapolated to Infinity (AUC (0-inf)) Following Single Dose Administration of Belantamab Mafodotin (ADC)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Pre-Dose; EOI; 1 h, 3 h, 8 h and 24 h post-EOI, Day 8, Day 15 in Cycle 1; Pre-Dose on Cycle 2 Day 1
Part 1: AUC From Time Zero to the Time of the Last Quantifiable Concentration (AUC (0 - Tlast)) Following Single Dose Administration of Belantamab Mafodotin (ADC)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Pre-Dose; EOI; 1 h, 3 h, 8 h and 24 h post-EOI, Day 8, Day 15 in Cycle 1; Pre-Dose on Cycle 2 Day 1
Part 1: Systemic Clearance (CL) Following Single Dose Administration of Belantamab Mafodotin (ADC)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Pre-Dose; EOI; 1 h, 3 h, 8 h and 24 h post-EOI, Day 8, Day 15 in Cycle 1; Pre-Dose on Cycle 2 Day 1
Part 1: Apparent Terminal Half-life (t1/2) Following Single Dose Administration of Belantamab Mafodotin (ADC)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Pre-Dose; EOI; 1 h, 3 h, 8 h and 24 h post-EOI, Day 8, Day 15 in Cycle 1; Pre-Dose on Cycle 2 Day 1
Part 1: Terminal Phase Rate Constant (Lambda_z) Following Single Dose Administration of Belantamab Mafodotin (ADC)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Pre-Dose; EOI; 1 h, 3 h, 8 h and 24 h post-EOI, Day 8, Day 15 in Cycle 1; Pre-Dose on Cycle 2 Day 1
Part 1: Volume of Distribution at Steady State (Vss) Following Single Dose Administration of Belantamab Mafodotin (ADC)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Pre-Dose; EOI; 1 h, 3 h, 8 h and 24 h post-EOI, Day 8, Day 15 in Cycle 1; Pre-Dose on Cycle 2 Day 1
Part 1: Time of Last Observed Quantifiable Concentration (Tlast) Following Single Dose Administration of Belantamab Mafodotin (ADC)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Pre-Dose; EOI; 1 h, 3 h, 8 h and 24 h post-EOI, Day 8, Day 15 in Cycle 1; Pre-Dose on Cycle 2 Day 1
Part 1: Time to Maximum Plasma Concentration (Tmax) Following Single Dose Administration of Belantamab Mafodotin (ADC)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Pre-Dose; EOI; 1 h, 3 h, 8 h and 24 h post-EOI, Day 8, Day 15 in Cycle 1; Pre-Dose on Cycle 2 Day 1
Part 1: Concentration at the End of Infusion (C-EOI) Following Repeat Dose Administration of Belantamab Mafodotin (ADC)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Cycle 1, Cycle 2, Cycle 3, Cycle 6, Cycle 9 and Cycle 12
Part 1: Maximum Observed Concentration (Cmax) Following Repeat Dose Administration of Belantamab Mafodotin (ADC)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Cycle 1, Cycle 2, Cycle 3, Cycle 6, Cycle 9 and Cycle 12
Part 1: Trough Plasma Concentration (Ctrough) Following Repeat Dose Administration of Belantamab Mafodotin (ADC)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Cycle 1, Cycle 2, Cycle 5, Cycle 8 and Cycle 11
Part 1: AUC (0-tau) Following Single Dose Administration of Belantamab Mafodotin (Total Antibody)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Pre-Dose; EOI; 1 h, 3 h, 8 h and 24 h post-EOI, Day 8, Day 15 in Cycle 1; Pre-Dose on Cycle 2 Day 1
Part 1: AUC (0-inf) Following Single Dose Administration of Belantamab Mafodotin (Total Antibody)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Pre-Dose; EOI; 1 h, 3 h, 8 h and 24 h post-EOI, Day 8, Day 15 in Cycle 1; Pre-Dose on Cycle 2 Day 1
Part 1: AUC (0 - Tlast) Following Single Dose Administration of Belantamab Mafodotin (Total Antibody)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Pre-Dose; EOI; 1 h, 3 h, 8 h and 24 h post-EOI, Day 8, Day 15 in Cycle 1; Pre-Dose on Cycle 2 Day 1
Part 1: Systemic Clearance (CL) Following Single Dose Administration of Belantamab Mafodotin (Total Antibody)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Pre-Dose; EOI; 1 h, 3 h, 8 h and 24 h post-EOI, Day 8, Day 15 in Cycle 1; Pre-Dose on Cycle 2 Day 1
Part 1: t1/2 Following Single Dose Administration of Belantamab Mafodotin (Total Antibody)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Pre-Dose; EOI; 1 h, 3 h, 8 h and 24 h post-EOI, Day 8, Day 15 in Cycle 1; Pre-Dose on Cycle 2 Day 1
Part 1: Lambda_z Following Single Dose Administration of Belantamab Mafodotin (Total Antibody)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Pre-Dose; EOI; 1 h, 3 h, 8 h and 24 h post-EOI, Day 8, Day 15 in Cycle 1; Pre-Dose on Cycle 2 Day 1
Part 1: Vss Following Single Dose Administration of Belantamab Mafodotin (Total Antibody)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Pre-Dose; EOI; 1 h, 3 h, 8 h and 24 h post-EOI, Day 8, Day 15 in Cycle 1; Pre-Dose on Cycle 2 Day 1
Part 1: Tlast Following Single Dose Administration of Belantamab Mafodotin (Total Antibody)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Pre-Dose; EOI; 1 h, 3 h, 8 h and 24 h post-EOI, Day 8, Day 15 in Cycle 1; Pre-Dose on Cycle 2 Day 1
Part 1: Tmax Following Single Dose Administration of Belantamab Mafodotin (Total Antibody)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Pre-Dose; EOI; 1 h, 3 h, 8 h and 24 h post-EOI, Day 8, Day 15 in Cycle 1; Pre-Dose on Cycle 2 Day 1
Part 1: C-EOI Following Repeat Dose Administration of Belantamab Mafodotin (Total Antibody)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Cycle 1, Cycle 2, Cycle 3, Cycle 6, Cycle 9 and Cycle 12
Part 1: Cmax Following Repeat Dose Administration of Belantamab Mafodotin (Total Antibody)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Cycle 1, Cycle 2, Cycle 3, Cycle 6, Cycle 9 and Cycle 12
Part 1: Ctrough Following Repeat Dose Administration of Belantamab Mafodotin (Total Antibody)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Cycle 1, Cycle 2, Cycle 5, Cycle 8 and Cycle 11
Part 1: AUC (0 - Tlast) Following Single Dose Administration of Belantamab Mafodotin Cysteine Maleimidocaproyl Monomethyl Auristatin F (Cys-mcMMAF)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Pre-Dose; EOI; 1 h, 3 h, 8 h and 24 h post-EOI, Day 8, Day 15 in Cycle 1; Pre-Dose on Cycle 2 Day 1
Part 1: Cmax Following Single Dose Administration of Belantamab Mafodotin (Cys-mcMMAF)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Pre-Dose; EOI; 1 h, 3 h, 8 h and 24 h post-EOI, Day 8, Day 15 in Cycle 1; Pre-Dose on Cycle 2 Day 1
Part 1: Tlast Following Single Dose Administration of Belantamab Mafodotin (Cys-mcMMAF)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Pre-Dose; EOI; 1 h, 3 h, 8 h and 24 h post-EOI, Day 8, Day 15 in Cycle 1; Pre-Dose on Cycle 2 Day 1
Part 1: Tmax Following Single Dose Administration of Belantamab Mafodotin (Cys-mcMMAF)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Pre-Dose; EOI; 1 h, 3 h, 8 h and 24 h post-EOI, Day 8, Day 15 in Cycle 1; Pre-Dose on Cycle 2 Day 1
Part 1: C-EOI Following Repeat Dose Administration of Belantamab Mafodotin (Cys-mcMMAF)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Cycle 1, Cycle 2, Cycle 3, Cycle 6, Cycle 9 and Cycle 12
Part 1: Ctrough Following Repeat Dose Administration of Belantamab Mafodotin (Cys-mcMMAF)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Cycle 1, Cycle 2, Cycle 5, Cycle 8 and Cycle 11
Part 1: Observed Accumulation Ratio of C-EOI (R(C-EOI)) Following Repeat Dose Administration of Belantamab Mafodotin (ADC)
Blood samples were collected for PK analysis. Accumulation ratio for C-EOI was calculated as C-EOI at the visit divided by C-EOI at Cycle 1.
Measured: Cycle 1, Cycle 2, Cycle 3, Cycle 6, Cycle 9 and Cycle 12
Part 1: Observed Accumulation Ratio of Ctrough (R(Ctrough)) Following Repeat Dose Administration of Belantamab Mafodotin (ADC)
Blood samples were collected for PK analysis. Accumulation ratio for Ctrough was calculated as Ctrough at the visit divided by pre-dose at Cycle 2 Day 1.
Measured: Cycle 1, Cycle 2, Cycle 5, Cycle 8 and Cycle 11
Part 1: Observed Accumulation Ratio of C-EOI (R(C-EOI)) Following Repeat Dose Administration of Belantamab Mafodotin (Total Antibody)
Blood samples were collected for PK analysis. Accumulation ratio for C-EOI was calculated as C-EOI at the visit divided by C-EOI at Cycle 1.
Measured: Cycle 1, Cycle 2, Cycle 3, Cycle 6, Cycle 9 and Cycle 12
Part 1: Observed Accumulation Ratio of Ctrough (R(Ctrough)) Following Repeat Dose Administration of Belantamab Mafodotin (Total Antibody)
Blood samples were collected for PK analysis. Accumulation ratio for Ctrough was calculated as Ctrough at the visit divided by pre-dose at Cycle 2 Day 1.
Measured: Cycle 1, Cycle 2, Cycle 5, Cycle 8 and Cycle 11
Part 1: Observed Accumulation Ratio of C-EOI (R(C-EOI)) Following Repeat Dose Administration of Belantamab Mafodotin (Cys-mcMMAF)
Blood samples were collected for PK analysis. Accumulation ratio for C-EOI was calculated as C-EOI at the visit divided by C-EOI at Cycle 1.
Measured: Cycle 1, Cycle 2, Cycle 3, Cycle 6, Cycle 9 and Cycle 12
Part 2: AUC (0-tau) Following Single Dose Administration of Belantamab Mafodotin (ADC)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Pre-dose, EOI, 2h and 24h post- Start of Infusion (SOI), Day 4, Day 8-15 in Cycle 1; Pre-Dose on Cycle 2 Day 1 (If Cycle 2 belantamab mafodotin dose was delayed, 1 PK sample was taken at 21 days post-SOI in Arm A or 28 days post-SOI in Arm B)
Part 2: AUC (0-inf) Following Single Dose Administration of Belantamab Mafodotin (ADC)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Pre-dose, EOI, 2h and 24h post- Start of Infusion (SOI), Day 4, Day 8-15 in Cycle 1; Pre-Dose on Cycle 2 Day 1 (If Cycle 2 belantamab mafodotin dose was delayed, 1 PK sample was taken at 21 days post-SOI in Arm A or 28 days post-SOI in Arm B)
Part 2: AUC (0 - Tlast) Following Single Dose Administration of Belantamab Mafodotin (ADC)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Pre-dose, EOI, 2h and 24h post- Start of Infusion (SOI), Day 4, Day 8-15 in Cycle 1; Pre-Dose on Cycle 2 Day 1 (If Cycle 2 belantamab mafodotin dose was delayed, 1 PK sample was taken at 21 days post-SOI in Arm A or 28 days post-SOI in Arm B)
Part 2: CL Following Single Dose Administration of Belantamab Mafodotin (ADC)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Pre-dose, EOI, 2h and 24h post- Start of Infusion (SOI), Day 4, Day 8-15 in Cycle 1; Pre-Dose on Cycle 2 Day 1 (If Cycle 2 belantamab mafodotin dose was delayed, 1 PK sample was taken at 21 days post-SOI in Arm A or 28 days post-SOI in Arm B)
Part 2: Cmax Following Repeat Dose Administration of Belantamab Mafodotin (ADC)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Pre-dose, EOI, 2h and 24h post- Start of Infusion (SOI), Day 4, Day 8-15 in Cycle 1; Pre-Dose on Cycle 2 Day 1 (If Cycle 2 belantamab mafodotin dose was delayed, 1 PK sample was taken at 21 days post-SOI in Arm A or 28 days post-SOI in Arm B)
Part 2: Lambda_z Following Single Dose Administration of Belantamab Mafodotin (ADC)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Pre-dose, EOI, 2h and 24h post- Start of Infusion (SOI), Day 4, Day 8-15 in Cycle 1; Pre-Dose on Cycle 2 Day 1 (If Cycle 2 belantamab mafodotin dose was delayed, 1 PK sample was taken at 21 days post-SOI in Arm A or 28 days post-SOI in Arm B)
Part 2: Vss Following Single Dose Administration of Belantamab Mafodotin (ADC)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Pre-dose, EOI, 2h and 24h post- Start of Infusion (SOI), Day 4, Day 8-15 in Cycle 1; Pre-Dose on Cycle 2 Day 1 (If Cycle 2 belantamab mafodotin dose was delayed, 1 PK sample was taken at 21 days post-SOI in Arm A or 28 days post-SOI in Arm B)
Part 2: t1/2 Following Single Dose Administration of Belantamab Mafodotin (ADC)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Pre-dose, EOI, 2h and 24h post- Start of Infusion (SOI), Day 4, Day 8-15 in Cycle 1; Pre-Dose on Cycle 2 Day 1 (If Cycle 2 belantamab mafodotin dose was delayed, 1 PK sample was taken at 21 days post-SOI in Arm A or 28 days post-SOI in Arm B)
Part 2: Tlast Following Single Dose Administration of Belantamab Mafodotin (ADC)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Pre-dose, EOI, 2h and 24h post- Start of Infusion (SOI), Day 4, Day 8-15 in Cycle 1; Pre-Dose on Cycle 2 Day 1 (If Cycle 2 belantamab mafodotin dose was delayed, 1 PK sample was taken at 21 days post-SOI in Arm A or 28 days post-SOI in Arm B)
Part 2: Tmax Following Single Dose Administration of Belantamab Mafodotin (ADC)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Pre-dose, EOI, 2h and 24h post- Start of Infusion (SOI), Day 4, Day 8-15 in Cycle 1; Pre-Dose on Cycle 2 Day 1 (If Cycle 2 belantamab mafodotin dose was delayed, 1 PK sample was taken at 21 days post-SOI in Arm A or 28 days post-SOI in Arm B)
Part 2 Arm A: C-EOI Following Repeat Dose Administration of Belantamab Mafodotin (ADC)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Cycle 1, Cycle 4, Cycle 6, Cycle 9, Cycle 10, Cycle 11 and Cycle 12
Part 2 Arm A: Ctrough Following Repeat Dose Administration of Belantamab Mafodotin (ADC)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Cycle 3, Cycle 5, Cycle 8, Cycle 9, Cycle 10 and Cycle 11
Part 2 Arm B: C-EOI Following Repeat Dose Administration of Belantamab Mafodotin (ADC)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Cycle 1, Cycle 2, Cycle 4, Cycle 10, Cycle 11 and Cycle 24
Part 2 Arm B: Ctrough Following Repeat Dose Administration of Belantamab Mafodotin (ADC)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Cycle 1, Cycle 3, Cycle 9, Cycle 10 and Cycle 23
Part 2: AUC (0-tau) Following Single Dose Administration of Belantamab Mafodotin (Total Antibody)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Pre-dose, EOI, 2h and 24h post- Start of Infusion (SOI), Day 4, Day 8-15 in Cycle 1; Pre-Dose on Cycle 2 Day 1 (If Cycle 2 belantamab mafodotin dose was delayed, 1 PK sample was taken at 21 days post-SOI in Arm A or 28 days post-SOI in Arm B)
Part 2: AUC (0-inf) Following Single Dose Administration of Belantamab Mafodotin (Total Antibody)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Pre-dose, EOI, 2h and 24h post- Start of Infusion (SOI), Day 4, Day 8-15 in Cycle 1; Pre-Dose on Cycle 2 Day 1 (If Cycle 2 belantamab mafodotin dose was delayed, 1 PK sample was taken at 21 days post-SOI in Arm A or 28 days post-SOI in Arm B)
Part 2: AUC (0 - Tlast) Following Single Dose Administration of Belantamab Mafodotin (Total Antibody)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Pre-dose, EOI, 2h and 24h post- Start of Infusion (SOI), Day 4, Day 8-15 in Cycle 1; Pre-Dose on Cycle 2 Day 1 (If Cycle 2 belantamab mafodotin dose was delayed, 1 PK sample was taken at 21 days post-SOI in Arm A or 28 days post-SOI in Arm B)
Part 2: Cmax Following Repeat Dose Administration of Belantamab Mafodotin (Total Antibody)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Pre-dose, EOI, 2h and 24h post- Start of Infusion (SOI), Day 4, Day 8-15 in Cycle 1; Pre-Dose on Cycle 2 Day 1 (If Cycle 2 belantamab mafodotin dose was delayed, 1 PK sample was taken at 21 days post-SOI in Arm A or 28 days post-SOI in Arm B)
Part 2: Lambda_z Following Single Dose Administration of Belantamab Mafodotin (Total Antibody)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Pre-dose, EOI, 2h and 24h post- Start of Infusion (SOI), Day 4, Day 8-15 in Cycle 1; Pre-Dose on Cycle 2 Day 1 (If Cycle 2 belantamab mafodotin dose was delayed, 1 PK sample was taken at 21 days post-SOI in Arm A or 28 days post-SOI in Arm B)
Part 2: Vss Following Single Dose Administration of Belantamab Mafodotin (Total Antibody)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Pre-dose, EOI, 2h and 24h post- Start of Infusion (SOI), Day 4, Day 8-15 in Cycle 1; Pre-Dose on Cycle 2 Day 1 (If Cycle 2 belantamab mafodotin dose was delayed, 1 PK sample was taken at 21 days post-SOI in Arm A or 28 days post-SOI in Arm B)
Part 2: t1/2 Following Single Dose Administration of Belantamab Mafodotin (Total Antibody)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Pre-dose, EOI, 2h and 24h post- Start of Infusion (SOI), Day 4, Day 8-15 in Cycle 1; Pre-Dose on Cycle 2 Day 1 (If Cycle 2 belantamab mafodotin dose was delayed, 1 PK sample was taken at 21 days post-SOI in Arm A or 28 days post-SOI in Arm B)
Part 2: Tlast Following Single Dose Administration of Belantamab Mafodotin (Total Antibody)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Pre-dose, EOI, 2h and 24h post- Start of Infusion (SOI), Day 4, Day 8-15 in Cycle 1; Pre-Dose on Cycle 2 Day 1 (If Cycle 2 belantamab mafodotin dose was delayed, 1 PK sample was taken at 21 days post-SOI in Arm A or 28 days post-SOI in Arm B)
Part 2: Tmax Following Single Dose Administration of Belantamab Mafodotin (Total Antibody)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Pre-dose, EOI, 2h and 24h post- Start of Infusion (SOI), Day 4, Day 8-15 in Cycle 1; Pre-Dose on Cycle 2 Day 1 (If Cycle 2 belantamab mafodotin dose was delayed, 1 PK sample was taken at 21 days post-SOI in Arm A or 28 days post-SOI in Arm B)
Part 2: Arm A: C-EOI Following Repeat Dose Administration of Belantamab Mafodotin (Total Antibody)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Cycle 1, Cycle 4, Cycle 6, Cycle 9, Cycle 10, Cycle 11 and Cycle 12
Part 2: Arm A: Ctrough Following Repeat Dose Administration of Belantamab Mafodotin (Total Antibody)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Cycle 3, Cycle 5, Cycle 8, Cycle 9, Cycle 10 and Cycle 11
Part 2: Arm B: C-EOI Following Repeat Dose Administration of Belantamab Mafodotin (Total Antibody)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Cycle 1, Cycle 2, Cycle 4, Cycle 10, Cycle 11 and Cycle 24
Part 2: Arm B: Ctrough Following Repeat Dose Administration of Belantamab Mafodotin (Total Antibody)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Cycle 1, Cycle 3, Cycle 9, Cycle 10 and Cycle 23
Part 2: AUC (0 - Tlast) Following Single Dose Administration of Belantamab Mafodotin (Cys-mcMMAF)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Pre-dose, EOI, 2h and 24h post- Start of Infusion (SOI), Day 4, Day 8-15 in Cycle 1; Pre-Dose on Cycle 2 Day 1 (If Cycle 2 belantamab mafodotin dose was delayed, 1 PK sample was taken at 21 days post-SOI in Arm A or 28 days post-SOI in Arm B)
Part 2: Cmax Following Repeat Dose Administration of Belantamab Mafodotin (Cys-mcMMAF)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Pre-dose, EOI, 2h and 24h post- Start of Infusion (SOI), Day 4, Day 8-15 in Cycle 1; Pre-Dose on Cycle 2 Day 1 (If Cycle 2 belantamab mafodotin dose was delayed, 1 PK sample was taken at 21 days post-SOI in Arm A or 28 days post-SOI in Arm B)
Part 2: Tlast Following Single Dose Administration of Belantamab Mafodotin (Cys-mcMMAF)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Pre-dose, EOI, 2h and 24h post- Start of Infusion (SOI), Day 4, Day 8-15 in Cycle 1; Pre-Dose on Cycle 2 Day 1 (If Cycle 2 belantamab mafodotin dose was delayed, 1 PK sample was taken at 21 days post-SOI in Arm A or 28 days post-SOI in Arm B)
Part 2: Tmax Following Single Dose Administration of Belantamab Mafodotin (Cys-mcMMAF)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Pre-dose, EOI, 2h and 24h post- Start of Infusion (SOI), Day 4, Day 8-15 in Cycle 1; Pre-Dose on Cycle 2 Day 1 (If Cycle 2 belantamab mafodotin dose was delayed, 1 PK sample was taken at 21 days post-SOI in Arm A or 28 days post-SOI in Arm B)
Part 2 Arm A: C-EOI Following Repeat Dose Administration of Belantamab Mafodotin (Cys-mcMMAF)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Cycle 1, Cycle 4, Cycle 6, Cycle 9, Cycle 10, Cycle 11 and Cycle 12
Part 2: Arm A: Ctrough Following Repeat Dose Administration of Belantamab Mafodotin (Cys-mcMMAF)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Cycle 3, Cycle 5, Cycle 8, Cycle 9, Cycle 10 and Cycle 11
Part 2: Arm B: C-EOI Following Repeat Dose Administration of Belantamab Mafodotin (Cys-mcMMAF)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Cycle 1, Cycle 2, Cycle 4, Cycle 10, Cycle 11 and Cycle 24
Part 2: Arm B: Ctrough Following Repeat Dose Administration of Belantamab Mafodotin (Cys-mcMMAF)
Blood samples were collected for PK analysis. PK parameter was determined using standard non-compartmental methods.
Measured: Cycle 1, Cycle 3, Cycle 9, Cycle 10 and Cycle 23
Part 1: Number of Participants With Anti-drug Antibodies (ADAs) Against Belantamab Mafodotin
Serum samples were collected and tested for the presence of antibodies against belantamab mafodotin.
Measured: Up to approximately 141 weeks
Part 2: Number of Participants With Anti-drug Antibodies (ADAs) Against Belantamab Mafodotin
Serum samples were collected and tested for the presence of antibodies against belantamab mafodotin.
Measured: Up to approximately 212 weeks
Part 1: Titers of ADAs Against Belantamab Mafodotin
Serum samples collected for the analysis of the presence of ADAs using validated immunoassays. All samples were to be further tested in screening assay, and positive samples were further to be characterized for antibody titers.
Measured: Up to approximately 141 weeks
Part 2: Titers of ADAs Against Belantamab Mafodotin
Serum samples collected for the analysis of the presence of ADAs using validated immunoassays. All samples were to be further tested in screening assay, and positive samples were further to be characterized for antibody titers.
Measured: Up to approximately 212 weeks
Part 1 - Percentage of Participants With Overall Response Rate (ORR)
ORR is defined as the percentage of participants with a confirmed partial response (PR) or better (i.e. PR, very good partial response [VGPR], complete response [CR], and stringent complete response [sCR]) of best response, according to the International Myeloma Working Group (IMWG) Response Criteria. CR = negative immunofixation of serum and urine AND disappearance of any soft tissue plasmacytomas AND <5% plasmacytomas in the bone marrow; sCR= CR as above PLUS normal serum free light-chain (FLC) assay ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence; VGPR = serum and urine M-component detectable by immunofixation but not on electrophoresis OR >= 90% reduction in serum M-component plus urine M-component <100 mg/24 hour (h); PR = >=50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by >=90% or to <200 mg/24 h.
Measured: Up to approximately 141 weeks
Part 2 - Percentage of Participants With ORR
ORR is defined as the percentage of participants with a confirmed PR or better (i.e. PR, VGPR, CR, and sCR) of best response, according to the IMWG Response Criteria. CR = negative immunofixation of serum and urine AND disappearance of any soft tissue plasmacytomas AND <5% plasmacytomas in the bone marrow; sCR= CR as above PLUS normal serum FLC assay ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence; VGPR = serum and urine M-component detectable by immunofixation but not on electrophoresis OR >= 90% reduction in serum M-component plus urine M-component <100 mg/24 h; PR = >=50% reduction of serum M-protein and reduction in 24-h urinary M-protein by >=90% or to <200 mg/24 h.
Measured: Up to approximately 212 weeks
Part 1: Clinical Benefit Rate (CBR)
CBR is defined as percentage of participants with a confirmed Minimal response (MR) or better (i.e. MR, PR, VGPR, CR, and sCR) of best response, according to the IMWG Response Criteria. CR = negative immunofixation of serum and urine AND disappearance of any soft tissue plasmacytomas AND <5% plasmacytomas in the bone marrow; sCR= CR as above PLUS normal serum FLC assay ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence; VGPR = serum and urine M-component detectable by immunofixation but not on electrophoresis OR >= 90% reduction in serum M-component plus urine M-component <100 mg/24 h; PR = >=50% reduction of serum M-protein and reduction in 24-h urinary M-protein by >=90% or to <200 mg/24 h; MR= >=25% but <=49% reduction of serum M-protein and reduction in 24-h urine M-protein by 50-89%. In addition to the above listed criteria, if present at baseline, >=50% reduction in the size (SPD) 4 of soft tissue plasmacytomas is also required.
Measured: Up to approximately 141 weeks
Part 2: Clinical Benefit Rate (CBR)
CBR is defined as percentage of participants with a confirmed Minimal response (MR) or better (i.e. MR, PR, VGPR, CR, and sCR) of best response, according to the IMWG Response Criteria. CR = negative immunofixation of serum and urine AND disappearance of any soft tissue plasmacytomas AND <5% plasmacytomas in the bone marrow; sCR= CR as above PLUS normal serum FLC assay ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence; VGPR = serum and urine M-component detectable by immunofixation but not on electrophoresis OR >= 90% reduction in serum M-component plus urine M-component <100 mg/24 h; PR = >=50% reduction of serum M-protein and reduction in 24-h urinary M-protein by >=90% or to <200 mg/24 h; MR= >=25% but <=49% reduction of serum M-protein and reduction in 24-h urine M-protein by 50-89%. In addition to the above listed criteria, if present at baseline, >=50% reduction in the size (SPD) 4 of soft tissue plasmacytomas is also required.
Measured: Up to approximately 212 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Feb 2019
- Study start14 Mar 2019
- Primary completion6 Apr 2023
- Study completion5 Sep 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Participants will receive GSK2857916 monotherapy during Part 1 (Dose escalation) of the study on a once every 21 days schedule. During Part 2, participants will receive GSK2857916 given in combination with Bortezomib/Dexamethasone on a once every 21 days schedule (Arm A) or with Pomalidomide/Dexamethasone on a once every 28 days schedule (Arm B).
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03828292
- Sponsor's protocol ID
- 207504
- Status last verified
- Jul 2025
- First submitted
- 31 Jan 2019
- Last updated
- 19 Aug 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: GSK will assess requests from qualified researchers for anonymized individual patient-level data and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.gsk-studyregister.com/About\_GSK\_Patient\_Level\_Data\_Sharing\_Final\_13July2023.pdf.
Publications
Sunami K, Iida S, Tsukada N, Fujii T, Kato H, Fukushima R, Wakabayashi S, Nakano H, Roy-Ghanta S, Kremer BE. DREAMM-11, Part 2: Japanese phase I trial of belantamab mafodotin combination therapies in relapsed/refractory multiple myeloma. Int J Hematol. 2025 Feb;121(2):174-186. doi: 10.1007/s12185-024-03889-8. Epub 2024 Dec 24.
PubMed 39718747