Non-Small Cell Lung CancerPhase 1/2NCT02424617
A Study of BGB324 (Bemcentinib) in Combination With Erlotinib in Patients With Non-Small Cell Lung Cancer
A Phase 1/2 study testing Erlotinib and Bemcentinib in people with Non-Small Cell Lung Cancer, run by BerGenBio ASA at 10 sites in United States.
Trial summary
A Phase 1/2 multi-center open-label study of BGB324 (bemcentinib) as a single agent (Run-in Cohort) and in combination with erlotinib (Arms A, B, and C) in participants with Stage IIIb or Stage IV non-small cell lung cancer (NSCLC). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Small Cell Lung Cancer
- What is being tested?
- Erlotinib and Bemcentinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 10 sitesUnited States
- Study dates
- 19 Apr 2015to 25 Aug 2021
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- Pregnant or lactating.
- Abnormal left ventricular ejection fraction (less than the lower limit of normal for a participants of that age at the treating institution or <45%).
- Treatment with any of the following; histamine receptor 2 inhibitors, proton pump inhibitors or antacids within 3 days or 5 half-lives, whichever is longer. The Investigator may initiate rescue treatment with these medications during the study, providing they are taken in the evening.
- History of an ischemic cardiac event, including myocardial infarction, within 3 months of consent.
- Pulmonary hemorrhage or hemoptysis >2.5 mL blood within 6 weeks of consent unless cause has been addressed and is medically resolved.
- Congestive cardiac failure of >Class II severity according to the New York Heart Association (NYHA) defined as symptomatic at less than ordinary levels of activity.
Show all 34Show fewer
- Unstable cardiac disease, including unstable angina or unstable hypertension, as defined by the need for change in medication for lack of disease control within 3 months of consent.
- History or presence of sustained bradycardia (≤ 60 bpm) or history of symptomatic bradycardia, left bundle branch block, cardiac pacemaker or significant atrial tachyarrhythmias, as defined by the need for treatment.
- tachyarrhythmias, as defined by the need for treatment.
- Current treatment with agents that may prolong QT interval and may cause Torsade de Points which cannot be discontinued at least 2 weeks prior to treatment.
- Known family or personal history of long QTc syndrome or ventricular arrhythmias including ventricular bigeminy.
- Previous history of ≥ Grade 3 drug-induced QTc prolongation.
- Screening 12-lead triplicate electrocardiogram (ECG) with an average measurable interval utilizing Fridericia's correction (QTcF) >450 ms.
- Inadequate liver function as demonstrated by:
- Serum bilirubin ≥ 1.5 times the upper limit of normal range (ULN); or
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥2.5 times the ULN (up to 5 times the ULN in the presence of liver metastases).
- Inability to tolerate oral medication.
- Impaired coagulation as evidenced by:
- International normalized ratio (INR) >1.5 times ULN (or equivalent); or
- Activated partial thromboplastin time (aPTT) >1.5 times ULN.
- Existing gastrointestinal disease affecting drug absorption, such as celiac disease or Crohn's disease.
- Previous bowel resection that may impair study drug absorption.
- Impaired renal function as demonstrated by creatinine clearance of ≤ 50 mL/min determined by Cockcroft Gault formula.
- Absolute neutrophil count <1.5 x 109/L, hemoglobin <9.0 g/dL, platelet count <100 x 109/L in the absence of blood product support.
- Any evidence of severe or uncontrolled systemic conditions (e.g., severe hepatic impairment) or current unstable or uncompensated respiratory or cardiac conditions which makes it undesirable for the participant to participate in the study or which could jeopardize compliance with the protocol.
- Treatment with any medication which is predominantly metabolized by CYP3A4 and has a narrow therapeutic index.
- Active, uncontrolled central nervous system (CNS) disease; (previously treated CNS metastases that are asymptomatic and do not require steroid treatment are allowed). Note: Participants with known CNS metastases who have completed radiotherapy at least 2 weeks prior to bemcentinib treatment are eligible.
- Known active infection with human immunodeficiency virus (HIV), hepatitis B or C viruses (screening not required):
- Participants who have a history of hepatitis B infection are eligible provided they are hepatitis B surface antigen negative.
- Participants who have a history of hepatitis C infection are eligible provided they have no evidence of hepatitis C ribonucleic acid using a quantitative polymerase chain reaction assay at least 6 months after completing treatment for hepatitis C infection.
- Major surgery requiring general anesthesia within 28 days prior to the start of bemcentinib, excluding biopsies and procedures for insertion of central venous access devices.
- Treatment with cytotoxic chemotherapy, within the 3 weeks prior to the first dose of bemcentinib (Cycle 1, Day 1) with the exception of treatment with other EGFR inhibitors which must be completed 1 week prior to commencing treatment with bemcentinib. There is no requirement to discontinue ongoing treatment with erlotinib.
- Treatment with other non-cytotoxic agents for NSCLC in the 10 days or 4 half-lives, prior to the first dose of bemcentinib (Cycle 1, Day 1) whichever is shorter.
- Prior biological therapies in the 4 weeks or 5 half-lives, whichever is shorter before the first dose of bemcentinib (Cycle 1, Day 1). Note prior treatment with an alternative EGFR inhibitor and/or programmed cell death protein 1 (PD-1) blockade is permitted.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Mary Crowley Cancer Research Centers
Dallas, Texas, 75230
Southwestern Medical Center
Dallas, Texas, 75390-8852
Henry Ford Health System
Detroit, Michigan, 48202
MD Anderson Cancer Center
Houston, Texas, 77030
Oncology Consultants PA
Houston, Texas, 77030
UC San Diego Moores Cancer Center
La Jolla, California, 92093-0698
Horizon Oncology Research,
Lafayette, Indiana, 47905
USC/Norris Comprehensive Cancer Center
Los Angeles, California, 90033
The Sarah Cannon Research Institute Tennessee Oncology PLLC
Nashville, Tennessee, 37203
Moffitt Cancer Center
Tampa, Florida, 33612
About this study
Official title: A Multi-Center Open-Label Phase 1/2 Study of BGB324 in Combination With Erlotinib in Patients With Stage IIIb or Stage IV Non-Small Cell Lung Cancer
A Phase 1/2 multi-center open-label study of BGB324 (bemcentinib) as a single agent (Run-in Cohort) and in combination with erlotinib (Arms A, B, and C) in participants with Stage IIIb or Stage IV non-small cell lung cancer (NSCLC). Bemcentinib is a potent selective small molecule inhibitor of AXL, a surface membrane protein kinase receptor which is connected with poor prognosis and acquired resistance to therapy.
Read the detailed description
This is a multi-center, multi-arm open-label Phase 1/2 study that was conducted at 10 clinical sites in the United States and in Europe.
Total 40 participants with histologically- or cytologically-confirmed Stage IIIb or Stage IV NSCLC received bemcentinib (BGB324) as a single agent (Run-in Cohort) or in combination with erlotinib (Arms A, B, and C).
Run-in Arm to establish the safety and tolerability of bemcentinib (BGB324) administered as a single agent; bemcentinib was administered at a loading dose of 600 mg on Day 1 and Day 2 of Cycle 1, followed by 200 mg daily thereafter. After 6 participants have been dosed and safety established; Arm A (dose escalation arm) was opened to confirm the bemcentinib dose to be used in combination with erlotinib.
In Arm A the dose of bemcentinib (BGB324) was escalated in a standard 3+3 fashion until a maximum tolerated dose (MTD) of the combination (bemcentinib + erlotinib) was established. The dose of bemcentinib to be investigated in Arm B and C was confirmed upon recommendation of a Safety Review Committee.
Arm B and C was open in parallel to investigate bemcentinib in combination with erlotinib.
- Conditions
- Non-Small Cell Lung Cancer
- Being tested
- Erlotinib, Bemcentinib
- Keywords
- BGB324, Bemcentinib, Erlotinib, NSCLC
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ErlotinibDrug
Also called Tarceva
Participants received erlotinib 150 mg for the 21-day cycle.
BemcentinibDrug
Also called BGB324
Participants received bemcentinib 600 mg on Days 1 and 2 as loading dose and bemcentinib 200 mg as daily maintenance dose for the 21-day cycle.
BemcentinibDrug
Also called BGB324
Participants received starting loading dose of bemcentinib 600 mg (200 mg on Days 1, 2 and 3) and bemcentinib 100 mg as daily maintenance dose for the 21-day cycle.
Depending on tolerability and DLT, the loading dose of bemcentinib was escalated to 800mg (400 mg on Days 1 and 2) and bemcentinib 100 mg as daily maintenance for the 21- day cycle and to 1200 mg daily (600 mg on Days 1 and 2, or 400 mg on Days 1, 2 and 3) and bemcentinib 200 mg as daily maintenance for the 21- day cycle).
BemcentinibDrug
Also called BGB324
Participants received bemcentinib 400 mg on Days 1, 2 and 3 as loading dose and bemcentinib 200 mg as daily maintenance dose for the 21-day cycle.
| Study group | Role | What they receive |
|---|---|---|
| Phase 1- Run in Arm (Bemcentinib Monotherapy) | Experimental | Participants in this arm received bemcentinib as monotherapy. This was to determine the safety and tolerability of bemcentinib when administered alone. Receives: Drug: Bemcentinib |
| Phase 1- Arm A (Bemcentinib + Erlotinib) | Experimental | Participants in this arm received erlotinib with bemcentinib. A standard 3+3 design to determine the dose of bemcentinib that could be safely administered in combination with erlotinib in participants who had received prior treatment with erlotinib. This was to determine the maximum tolerated dose of bemcentinib that could be safely administered with erlotinib. Receives: Drug: Erlotinib; Drug: Bemcentinib |
| Phase 2- Arm B (Bemcentinib + Erlotinib) | Experimental | Participants in this arm received erlotinib with bemcentinib in participants with an activating epidermal growth factor receptor (EGFR) mutation who are T790M negative and who had progressed after receiving treatment with an approved EGFR tyrosine kinase inhibitor (TKI) [osimertinib, afatinib, or gefitinib]. Receives: Drug: Erlotinib; Drug: Bemcentinib |
| Phase 2- Arm C (Bemcentinib + Erlotinib) | Experimental | Participants in this arm received erlotinib daily along with bemcentinib in participants with an activating EGFR mutation (including exon 19 deletion or exon 21 [L858R] substitution or other rearrangement of the EGFR gene mutation) who had received greater than or equal to (≥) 12 weeks of erlotinib without disease progression. Receives: Drug: Erlotinib; Drug: Bemcentinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-emergent Adverse Events (TEAE)
An adverse event (AE) is any untoward medical occurrence in participants, temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAEs were defined as AEs that occurred from the first dose of study drug administration up to 28-days post last dose of study drug.
Measured: First dose of study drug to 28 days post last dose (maximum study treatment exposure was 1554 days; maximum follow-up = 1582 days)
Number of Participants With Clinically Significant Laboratory Abnormalities
Laboratory evaluation: assessment of hematology, clinical chemistry, coagulation, and urinalysis. Hematology assessment: full blood count including differential white cell count, hemoglobin, hematocrit and platelets. Clinical chemistry assessment: potassium, calcium, uric acid, electrolytes, blood urea nitrogen, total protein, total bilirubin, alanine aminotransferase, aspartate aminotransferase, creatinine, creatine phosphokinase, alkaline phosphatase, albumin, phosphorus, glucose, magnesium plus amylase and lipase. Coagulation assessment: prothrombin time and/or international normalized ratio, activated partial thromboplastin time. Urinalysis: dipstick measurement of blood, nitrite, glucose, ketones, leukocytes, protein, and pH. Clinical significance was determined based on investigator's decision. In this outcome measure number of participants with clinically significant abnormalities in assessment of hematology, clinical chemistry, coagulation, and urinalysis are reported.
Measured: First dose of study drug to 28 days post last dose (maximum study treatment exposure was 1554 days; maximum follow-up = 1582 days)
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status at End of Study
The ECOG performance status was scored on a scale of Grade 0 to 5, where: 0 = Fully active, able to carry on all pre-disease performance without restriction; 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g. light house work, office work; 2 = Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours; 3 = Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours; 4 = Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair; 5 = Dead. Higher scores indicated worse condition. Number of participants with each ECOG Grade were reported.
Measured: End of study visit was 28 days post last dose (maximum study treatment exposure was 1554 days; maximum follow-up = 1582 days)
Number of Participants With Clinically Significant Change From Baseline in Physical Examination, Vital Signs, and 12- Lead Triplicate Electrocardiogram (ECG) Parameters up to End of Study
Number of participants with clinically significant change from baseline in physical examination, vital signs (including blood pressure, pulse, respiratory rate and oral temperature) and 12-lead triplicate ECG parameters was reported. Clinically significant abnormalities were based on the investigator's decision.
Measured: Baseline up to end of the study (28 days post last dose; maximum study treatment exposure was 1554 days; maximum follow-up = 1582 days)
Number of Participants With Clinically Significant Abnormalities in Echocardiogram and Multi-gated Acquisition (MUGA) Scan
Number of participants with clinically significant abnormalities in echocardiogram and MUGA scan was reported. MUGA scan is used to measure the ejection fraction, which reports how well heart is functioning. Clinically significant abnormalities were based on the investigator's decision.
Measured: First dose of study drug to 28 days post last dose (maximum study treatment exposure was 1554 days; maximum follow-up = 1582 days)
Secondary outcomes (8)
Area Under the Curve (AUC) Over 24 Hours at Steady State of Bemcentinib
The AUC is defined as the area under the curve over 24 hours at steady state. The AUC 0- 24 hours using the linear trapezoidal method was summarized using the predicted plasma concentrations at steady state.
Measured: Arm A only: Cycle(C)1 Day(D)1: Predose, 2, 4, 6, 8 & 24h post-dose; Arm B only: C1D1 & D2: Predose; Arms A&B: C1D8: Predose, 2, 4, 6, 8 & 24h post-dose: C1D15, C2D1,8 & 15, C3D1: Predose and End of Study
Maximum Observed Plasma Concentration (Cmax) of Bemcentinib
Cmax was defined as the observed maximum plasma concentration after single dose administration. Cmax was summarized using the predicted plasma concentrations at steady state.
Measured: Arm A only: Cycle(C)1 Day(D)1: Predose, 2, 4, 6, 8 & 24h post-dose; Arm B only: C1D1 & D2: Predose; Arms A&B: C1D8: Predose, 2, 4, 6, 8 & 24h post-dose: C1D15, C2D1,8 & 15, C3D1: Predose and End of Study
Time to Reach Maximum Plasma Concentration (Tmax) of Bemcentinib
The Tmax defined as the time taken to reach Cmax. The Tmax was summarized using the predicted plasma concentrations at steady state.
Measured: Arm A only: Cycle(C)1 Day(D)1: Predose, 2, 4, 6, 8 & 24h post-dose; Arm B only: C1D1 & D2: Predose; Arms A&B: C1D8: Predose, 2, 4, 6, 8 & 24h post-dose: C1D15, C2D1,8 & 15, C3D1: Predose and End of Study
AUC Over 24 Hours at Steady State of Erlotinib
The AUC 0-24 is defined as the area under the curve over 24 hours at steady state. The AUC 0- 24 hours using the linear trapezoidal method was summarized using the predicted plasma concentrations at steady state.
Measured: At Day 8 (in Cycle 1): pre-dose, 2, 4, 6, 8 and 24 hours post-dose (cycle length=21 days)
Cmax of Erlotinib
Cmax was defined as the observed maximum plasma concentration after single dose administration. Cmax was summarized using the predicted plasma concentrations at steady state.
Measured: At Day 1 and 8 (in Cycle 1): pre-dose, 2, 4, 6, 8 and 24 hours post-dose (cycle length=21 days)
Tmax of Erlotinib
The Tmax defined as the time taken to reach Cmax. The Tmax was summarized using the predicted plasma concentrations at steady state.
Measured: At Day 1 and 8 (in Cycle 1): pre-dose, 2, 4, 6, 8 and 24 hours post-dose (cycle length=21 days)
Dose Limiting Toxicity (DLT) Assessment
DLTs included any non-hematological toxicity ≥ Grade 3 except Grade 3 nausea, vomiting or diarrhea that resolved within 72 hours with optimal therapy: Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding. Grade 4 neutropenia persisting for ≥ 5 days or Grade 3 or 4 febrile neutropenia. Treatment discontinuation or dose reduction for greater than (>) 72 hours during the first cycle as a result of treatment-related toxicity. DLTs were evaluated using National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) Version 4.03. Number of participants that reported DLTs were reported in this outcome measure.
Measured: First dose of study drug to 28 days post last dose (maximum study treatment exposure was 1554 days; maximum follow-up = 1582 days)
Time To Progression (TTP)
TTP was calculated as the duration from the date of first administration of bemcentinib to the date of radiological progression of disease first observed, according to the overall response evaluation (progressive disease, measurement proven or progressive disease, symptomatic deterioration). If a participant died without any radiological assessment, the progressive disease date was date of death. Progression was assessed using the Response evaluation criteria in solid tumors (RECIST) version 1.1 criteria.
Measured: First dose of bemcentinib to first radiological progression (maximum study treatment exposure was 1554 days; maximum follow-up = 1582 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2015 (estimated)
- Study start19 Apr 2015
- Primary completion25 Aug 2021
- Study completion25 Aug 2021
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 (10)Papers the sponsor has linked to this study.
- Other trials for Non-Small Cell Lung CancerStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- BerGenBio ASA
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Dr. Lauren Byers, MD, Principal investigator, MD, Anderson Cancer Centre Houston, Texas
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02424617
- Sponsor's protocol ID
- BGBC004
- Status last verified
- Feb 2025
- First submitted
- 9 Apr 2015
- Last updated
- 26 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in the article, after deidentification \[text, tables, figures and appendices\].
Publications
Hector A, Montgomery EA, Karikari C, Canto M, Dunbar KB, Wang JS, Feldmann G, Hong SM, Haffner MC, Meeker AK, Holland SJ, Yu J, Heckrodt TJ, Zhang J, Ding P, Goff D, Singh R, Roa JC, Marimuthu A, Riggins GJ, Eshleman JR, Nelkin BD, Pandey A, Maitra A. The Axl receptor tyrosine kinase is an adverse prognostic factor and a therapeutic target in esophageal adenocarcinoma. Cancer Biol Ther. 2010 Nov 15;10(10):1009-18. doi: 10.4161/cbt.10.10.13248. Epub 2010 Nov 15.
PubMed 20818175Brand TM, Iida M, Stein AP, Corrigan KL, Braverman CM, Luthar N, Toulany M, Gill PS, Salgia R, Kimple RJ, Wheeler DL. AXL mediates resistance to cetuximab therapy. Cancer Res. 2014 Sep 15;74(18):5152-64. doi: 10.1158/0008-5472.CAN-14-0294. Epub 2014 Aug 18.
PubMed 25136066Byers LA, Diao L, Wang J, Saintigny P, Girard L, Peyton M, Shen L, Fan Y, Giri U, Tumula PK, Nilsson MB, Gudikote J, Tran H, Cardnell RJ, Bearss DJ, Warner SL, Foulks JM, Kanner SB, Gandhi V, Krett N, Rosen ST, Kim ES, Herbst RS, Blumenschein GR, Lee JJ, Lippman SM, Ang KK, Mills GB, Hong WK, Weinstein JN, Wistuba II, Coombes KR, Minna JD, Heymach JV. An epithelial-mesenchymal transition gene signature predicts resistance to EGFR and PI3K inhibitors and identifies Axl as a therapeutic target for overcoming EGFR inhibitor resistance. Clin Cancer Res. 2013 Jan 1;19(1):279-90. doi: 10.1158/1078-0432.CCR-12-1558. Epub 2012 Oct 22.
PubMed 23091115Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.
PubMed 19097774Ishikawa M, Sonobe M, Nakayama E, Kobayashi M, Kikuchi R, Kitamura J, Imamura N, Date H. Higher expression of receptor tyrosine kinase Axl, and differential expression of its ligand, Gas6, predict poor survival in lung adenocarcinoma patients. Ann Surg Oncol. 2013 Dec;20 Suppl 3(Suppl 3):S467-76. doi: 10.1245/s10434-012-2795-3. Epub 2012 Dec 16.
PubMed 23242819Korshunov VA. Axl-dependent signalling: a clinical update. Clin Sci (Lond). 2012 Apr;122(8):361-8. doi: 10.1042/CS20110411.
PubMed 22187964Liu L, Greger J, Shi H, Liu Y, Greshock J, Annan R, Halsey W, Sathe GM, Martin AM, Gilmer TM. Novel mechanism of lapatinib resistance in HER2-positive breast tumor cells: activation of AXL. Cancer Res. 2009 Sep 1;69(17):6871-8. doi: 10.1158/0008-5472.CAN-08-4490. Epub 2009 Aug 11.
PubMed 19671800Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982 Dec;5(6):649-55. No abstract available.
PubMed 7165009Zhang Z, Lee JC, Lin L, Olivas V, Au V, LaFramboise T, Abdel-Rahman M, Wang X, Levine AD, Rho JK, Choi YJ, Choi CM, Kim SW, Jang SJ, Park YS, Kim WS, Lee DH, Lee JS, Miller VA, Arcila M, Ladanyi M, Moonsamy P, Sawyers C, Boggon TJ, Ma PC, Costa C, Taron M, Rosell R, Halmos B, Bivona TG. Activation of the AXL kinase causes resistance to EGFR-targeted therapy in lung cancer. Nat Genet. 2012 Jul 1;44(8):852-60. doi: 10.1038/ng.2330.
PubMed 22751098Thiele S, Baschant U, Rauch A, Rauner M. Instructions for producing a mouse model of glucocorticoid-induced osteoporosis. Bonekey Rep. 2014 Jul 2;3:552. doi: 10.1038/bonekey.2014.47. eCollection 2014.
PubMed 25120909
Study at a glance
From the registry record, last updated by the sponsor on 26 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-Center Open-Label Phase 1/2 Study of BGB324 in Combination With Erlotinib in Patients With Stage IIIb or Stage IV Non-Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT02424617
- Acronym / sponsor ID
- BGBC004
- Conditions
- Non-Small Cell Lung Cancer
- Keywords
- BGB324, Bemcentinib, Erlotinib, NSCLC
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- BerGenBio ASAIndustry (pharma, biotech, devices)
- Study start
- 19 Apr 2015 (actual)
- Primary completion
- 25 Aug 2021 (actual)
- Study completion
- 25 Aug 2021 (actual)
- First posted
- 23 Apr 2015 (estimated)
- Results
- Posted 26 Feb 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A Phase 1/2 multi-center open-label study of BGB324 (bemcentinib) as a single agent (Run-in Cohort) and in combination with erlotinib (Arms A, B, and C) in participants with Stage IIIb or Stage IV non-small cell lung cancer (NSCLC). Bemcentinib is a potent selective small molecule inhibitor of AXL, a surface membrane protein kinase receptor which is connected with poor prognosis and acquired resistance to therapy.
Detailed description
This is a multi-center, multi-arm open-label Phase 1/2 study that was conducted at 10 clinical sites in the United States and in Europe.
Total 40 participants with histologically- or cytologically-confirmed Stage IIIb or Stage IV NSCLC received bemcentinib (BGB324) as a single agent (Run-in Cohort) or in combination with erlotinib (Arms A, B, and C).
Run-in Arm to establish the safety and tolerability of bemcentinib (BGB324) administered as a single agent; bemcentinib was administered at a loading dose of 600 mg on Day 1 and Day 2 of Cycle 1, followed by 200 mg daily thereafter. After 6 participants have been dosed and safety established; Arm A (dose escalation arm) was opened to confirm the bemcentinib dose to be used in combination with erlotinib.
In Arm A the dose of bemcentinib (BGB324) was escalated in a standard 3+3 fashion until a maximum tolerated dose (MTD) of the combination (bemcentinib + erlotinib) was established. The dose of bemcentinib to be investigated in Arm B and C was confirmed upon recommendation of a Safety Review Committee.
Arm B and C was open in parallel to investigate bemcentinib in combination with erlotinib.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Phase 1- Run in Arm (Bemcentinib Monotherapy) | Experimental | Drug: BemcentinibParticipants in this arm received bemcentinib as monotherapy. This was to determine the safety and tolerability of bemcentinib when administered alone. |
| Phase 1- Arm A (Bemcentinib + Erlotinib) | Experimental | Drug: Erlotinib, Drug: BemcentinibParticipants in this arm received erlotinib with bemcentinib. A standard 3+3 design to determine the dose of bemcentinib that could be safely administered in combination with erlotinib in participants who had received prior treatment with erlotinib. This was to determine the maximum tolerated dose of bemcentinib that could be safely administered with erlotinib. |
| Phase 2- Arm B (Bemcentinib + Erlotinib) | Experimental | Drug: Erlotinib, Drug: BemcentinibParticipants in this arm received erlotinib with bemcentinib in participants with an activating epidermal growth factor receptor (EGFR) mutation who are T790M negative and who had progressed after receiving treatment with an approved EGFR tyrosine kinase inhibitor (TKI) [osimertinib, afatinib, or gefitinib]. |
| Phase 2- Arm C (Bemcentinib + Erlotinib) | Experimental | Drug: Erlotinib, Drug: BemcentinibParticipants in this arm received erlotinib daily along with bemcentinib in participants with an activating EGFR mutation (including exon 19 deletion or exon 21 [L858R] substitution or other rearrangement of the EGFR gene mutation) who had received greater than or equal to (≥) 12 weeks of erlotinib without disease progression. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (34 listed)
- Pregnant or lactating.
- Abnormal left ventricular ejection fraction (less than the lower limit of normal for a participants of that age at the treating institution or <45%).
- Treatment with any of the following; histamine receptor 2 inhibitors, proton pump inhibitors or antacids within 3 days or 5 half-lives, whichever is longer. The Investigator may initiate rescue treatment with these medications during the study, providing they are taken in the evening.
- History of an ischemic cardiac event, including myocardial infarction, within 3 months of consent.
- Pulmonary hemorrhage or hemoptysis >2.5 mL blood within 6 weeks of consent unless cause has been addressed and is medically resolved.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ErlotinibAlso: TarcevaParticipants received erlotinib 150 mg for the 21-day cycle. | Drug | Phase 1- Arm A (Bemcentinib + Erlotinib), Phase 2- Arm B (Bemcentinib + Erlotinib), Phase 2- Arm C (Bemcentinib + Erlotinib) |
| BemcentinibAlso: BGB324Participants received bemcentinib 600 mg on Days 1 and 2 as loading dose and bemcentinib 200 mg as daily maintenance dose for the 21-day cycle. | Drug | Phase 1- Run in Arm (Bemcentinib Monotherapy) |
| BemcentinibAlso: BGB324Participants received starting loading dose of bemcentinib 600 mg (200 mg on Days 1, 2 and 3) and bemcentinib 100 mg as daily maintenance dose for the 21-day cycle. Depending on tolerability and DLT, the loading dose of bemcentinib was escalated to 800mg (400 mg on Days 1 and 2) and bemcentinib 100 mg as daily maintenance for the 21- day cycle and to 1200 mg daily (600 mg on Days 1 and 2, or 400 mg on Days 1, 2 and 3) and bemcentinib 200 mg as daily maintenance for the 21- day cycle). | Drug | Phase 1- Arm A (Bemcentinib + Erlotinib) |
| BemcentinibAlso: BGB324Participants received bemcentinib 400 mg on Days 1, 2 and 3 as loading dose and bemcentinib 200 mg as daily maintenance dose for the 21-day cycle. | Drug | Phase 2- Arm B (Bemcentinib + Erlotinib), Phase 2- Arm C (Bemcentinib + Erlotinib) |
Primary outcome
Number of Participants With Treatment-emergent Adverse Events (TEAE)
Time frame: First dose of study drug to 28 days post last dose (maximum study treatment exposure was 1554 days; maximum follow-up = 1582 days)
An adverse event (AE) is any untoward medical occurrence in participants, temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAEs were defined as AEs that occurred from the first dose of study drug administration up to 28-days post last dose of study drug.
Number of Participants With Clinically Significant Laboratory Abnormalities
Time frame: First dose of study drug to 28 days post last dose (maximum study treatment exposure was 1554 days; maximum follow-up = 1582 days)
Laboratory evaluation: assessment of hematology, clinical chemistry, coagulation, and urinalysis. Hematology assessment: full blood count including differential white cell count, hemoglobin, hematocrit and platelets. Clinical chemistry assessment: potassium, calcium, uric acid, electrolytes, blood urea nitrogen, total protein, total bilirubin, alanine aminotransferase, aspartate aminotransferase, creatinine, creatine phosphokinase, alkaline phosphatase, albumin, phosphorus, glucose, magnesium plus amylase and lipase. Coagulation assessment: prothrombin time and/or international normalized ratio, activated partial thromboplastin time. Urinalysis: dipstick measurement of blood, nitrite, glucose, ketones, leukocytes, protein, and pH. Clinical significance was determined based on investigator's decision. In this outcome measure number of participants with clinically significant abnormalities in assessment of hematology, clinical chemistry, coagulation, and urinalysis are reported.
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status at End of Study
Time frame: End of study visit was 28 days post last dose (maximum study treatment exposure was 1554 days; maximum follow-up = 1582 days)
The ECOG performance status was scored on a scale of Grade 0 to 5, where: 0 = Fully active, able to carry on all pre-disease performance without restriction; 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g. light house work, office work; 2 = Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours; 3 = Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours; 4 = Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair; 5 = Dead. Higher scores indicated worse condition. Number of participants with each ECOG Grade were reported.
Number of Participants With Clinically Significant Change From Baseline in Physical Examination, Vital Signs, and 12- Lead Triplicate Electrocardiogram (ECG) Parameters up to End of Study
Time frame: Baseline up to end of the study (28 days post last dose; maximum study treatment exposure was 1554 days; maximum follow-up = 1582 days)
Number of participants with clinically significant change from baseline in physical examination, vital signs (including blood pressure, pulse, respiratory rate and oral temperature) and 12-lead triplicate ECG parameters was reported. Clinically significant abnormalities were based on the investigator's decision.
Number of Participants With Clinically Significant Abnormalities in Echocardiogram and Multi-gated Acquisition (MUGA) Scan
Time frame: First dose of study drug to 28 days post last dose (maximum study treatment exposure was 1554 days; maximum follow-up = 1582 days)
Number of participants with clinically significant abnormalities in echocardiogram and MUGA scan was reported. MUGA scan is used to measure the ejection fraction, which reports how well heart is functioning. Clinically significant abnormalities were based on the investigator's decision.
8 secondary outcomes
Area Under the Curve (AUC) Over 24 Hours at Steady State of Bemcentinib
Time frame: Arm A only: Cycle(C)1 Day(D)1: Predose, 2, 4, 6, 8 & 24h post-dose; Arm B only: C1D1 & D2: Predose; Arms A&B: C1D8: Predose, 2, 4, 6, 8 & 24h post-dose: C1D15, C2D1,8 & 15, C3D1: Predose and End of Study
Maximum Observed Plasma Concentration (Cmax) of Bemcentinib
Time frame: Arm A only: Cycle(C)1 Day(D)1: Predose, 2, 4, 6, 8 & 24h post-dose; Arm B only: C1D1 & D2: Predose; Arms A&B: C1D8: Predose, 2, 4, 6, 8 & 24h post-dose: C1D15, C2D1,8 & 15, C3D1: Predose and End of Study
Time to Reach Maximum Plasma Concentration (Tmax) of Bemcentinib
Time frame: Arm A only: Cycle(C)1 Day(D)1: Predose, 2, 4, 6, 8 & 24h post-dose; Arm B only: C1D1 & D2: Predose; Arms A&B: C1D8: Predose, 2, 4, 6, 8 & 24h post-dose: C1D15, C2D1,8 & 15, C3D1: Predose and End of Study
AUC Over 24 Hours at Steady State of Erlotinib
Time frame: At Day 8 (in Cycle 1): pre-dose, 2, 4, 6, 8 and 24 hours post-dose (cycle length=21 days)
Cmax of Erlotinib
Time frame: At Day 1 and 8 (in Cycle 1): pre-dose, 2, 4, 6, 8 and 24 hours post-dose (cycle length=21 days)
Tmax of Erlotinib
Time frame: At Day 1 and 8 (in Cycle 1): pre-dose, 2, 4, 6, 8 and 24 hours post-dose (cycle length=21 days)
Dose Limiting Toxicity (DLT) Assessment
Time frame: First dose of study drug to 28 days post last dose (maximum study treatment exposure was 1554 days; maximum follow-up = 1582 days)
Time To Progression (TTP)
Time frame: First dose of bemcentinib to first radiological progression (maximum study treatment exposure was 1554 days; maximum follow-up = 1582 days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Feb 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 20818175Hector A, Montgomery EA, Karikari C, Canto M, Dunbar KB, Wang JS, Feldmann G, Hong SM, Haffner MC, Meeker AK, Holland SJ, Yu J, Heckrodt TJ, Zhang J, Ding P, Goff D, Singh R, Roa JC, Marimuthu A, Riggins GJ, Eshleman JR, Nelkin BD, Pandey A, Maitra A. The Axl receptor tyrosine kinase is an adverse prognostic factor and a therapeutic target in esophageal adenocarcinoma. Cancer Biol Ther. 2010 Nov 15;10(10):1009-18. doi: 10.4161/cbt.10.10.13248. Epub 2010 Nov 15.
- Background: PubMed 25136066Brand TM, Iida M, Stein AP, Corrigan KL, Braverman CM, Luthar N, Toulany M, Gill PS, Salgia R, Kimple RJ, Wheeler DL. AXL mediates resistance to cetuximab therapy. Cancer Res. 2014 Sep 15;74(18):5152-64. doi: 10.1158/0008-5472.CAN-14-0294. Epub 2014 Aug 18.
- Background: PubMed 23091115Byers LA, Diao L, Wang J, Saintigny P, Girard L, Peyton M, Shen L, Fan Y, Giri U, Tumula PK, Nilsson MB, Gudikote J, Tran H, Cardnell RJ, Bearss DJ, Warner SL, Foulks JM, Kanner SB, Gandhi V, Krett N, Rosen ST, Kim ES, Herbst RS, Blumenschein GR, Lee JJ, Lippman SM, Ang KK, Mills GB, Hong WK, Weinstein JN, Wistuba II, Coombes KR, Minna JD, Heymach JV. An epithelial-mesenchymal transition gene signature predicts resistance to EGFR and PI3K inhibitors and identifies Axl as a therapeutic target for overcoming EGFR inhibitor resistance. Clin Cancer Res. 2013 Jan 1;19(1):279-90. doi: 10.1158/1078-0432.CCR-12-1558. Epub 2012 Oct 22.
- Background: PubMed 19097774Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.
- Background: PubMed 23242819Ishikawa M, Sonobe M, Nakayama E, Kobayashi M, Kikuchi R, Kitamura J, Imamura N, Date H. Higher expression of receptor tyrosine kinase Axl, and differential expression of its ligand, Gas6, predict poor survival in lung adenocarcinoma patients. Ann Surg Oncol. 2013 Dec;20 Suppl 3(Suppl 3):S467-76. doi: 10.1245/s10434-012-2795-3. Epub 2012 Dec 16.
- Background: PubMed 22187964Korshunov VA. Axl-dependent signalling: a clinical update. Clin Sci (Lond). 2012 Apr;122(8):361-8. doi: 10.1042/CS20110411.
- Background: PubMed 19671800Liu L, Greger J, Shi H, Liu Y, Greshock J, Annan R, Halsey W, Sathe GM, Martin AM, Gilmer TM. Novel mechanism of lapatinib resistance in HER2-positive breast tumor cells: activation of AXL. Cancer Res. 2009 Sep 1;69(17):6871-8. doi: 10.1158/0008-5472.CAN-08-4490. Epub 2009 Aug 11.
- Background: PubMed 7165009Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982 Dec;5(6):649-55. No abstract available.
- Background: PubMed 22751098Zhang Z, Lee JC, Lin L, Olivas V, Au V, LaFramboise T, Abdel-Rahman M, Wang X, Levine AD, Rho JK, Choi YJ, Choi CM, Kim SW, Jang SJ, Park YS, Kim WS, Lee DH, Lee JS, Miller VA, Arcila M, Ladanyi M, Moonsamy P, Sawyers C, Boggon TJ, Ma PC, Costa C, Taron M, Rosell R, Halmos B, Bivona TG. Activation of the AXL kinase causes resistance to EGFR-targeted therapy in lung cancer. Nat Genet. 2012 Jul 1;44(8):852-60. doi: 10.1038/ng.2330.
- Background: PubMed 25120909Thiele S, Baschant U, Rauch A, Rauner M. Instructions for producing a mouse model of glucocorticoid-induced osteoporosis. Bonekey Rep. 2014 Jul 2;3:552. doi: 10.1038/bonekey.2014.47. eCollection 2014.
- Please see BerGenBio's website for more information.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported in the article, after deidentification [text, tables, figures and appendices].
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dr. Lauren Byers, MD principal investigator
MD, Anderson Cancer Centre Houston, Texas
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Erlotinib and Bemcentinib in people with Non-Small Cell Lung Cancer, run by BerGenBio ASA at 10 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment-emergent Adverse Events (TEAE) (time frame: First dose of study drug to 28 days post last dose (maximum study treatment exposure was 1554 days; maximum follow-up = 1582 days)). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02424617, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Feb 2025.