Diffuse Large B-cell LymphomaPhase 1/2NCT04358458
First-in-Human (FIH) Trial of GEN3009 in Subjects With Relapsed or Refractory B-Cell Non-Hodgkin Lymphomas
A Phase 1/2 study testing GEN3009 and Epcoritamab in people with Diffuse Large B-cell Lymphoma and Follicular Lymphoma, run by Genmab at 17 sites in 5 countries.
Trial summary
The drug that will be investigated in the study is an antibody, GEN3009. Since this is the first study of GEN3009 in humans, the main purpose is to evaluate safety. Besides safety, the study will determine the recommended GEN3009 dose to be tested in a larger group of patients and assess preliminary clinical activity… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diffuse Large B-cell Lymphoma, Follicular Lymphoma, Marginal Zone Lymphoma
- What is being tested?
- GEN3009 and Epcoritamab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 46 participants
- Where
- 17 sitesin 5 countries
- Study dates
- 13 Mar 2020to 28 Jul 2023
- 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
- Be at least 18 years of age.
- Must sign an informed consent form prior to any screening procedures.
- Dose Escalation: Has histologically or cytologically confirmed relapsed and/or refractory B-cell NHL with no available standard therapy or is not a candidate for available standard therapy, and for whom, in the opinion of the investigator, the experimental therapy may be beneficial. All subjects must have received at least two prior lines of systemic therapy.
- Dose Expansion: Has histologically or cytologically confirmed relapsed or refractory B-cell NHL. All subjects must have received at least 2 prior lines of systemic therapy, and,
- For FL and DLBCL, at least 1 of the 2 prior lines of treatment must have been a CD20 containing systemic regimen;
- For CLL, subjects must have received at least one prior line of BTK inhibitor or BCL 2 inhibitor.
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- Has one of the eligible subtypes of B-cell NHL :
- Dose Escalation: (DLBCL, HGBCL, PMBCL, FL, MCL, MZL, SLL, or CLL). Dose Expansion: (DLBCL, FL, CLL)
- Has measurable disease for B-cell NHL or has active disease for Chronic Lymphocytic Leukemia (CLL).
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
- Has adequate hepatic, renal, and bone marrow functions.
- Before the first dose of GEN3009, during the trial, and for 12 months after the last dose of GEN3009 and/or the combination, a woman must be either not of childbearing potential or of childbearing potential and practicing a highly effective method of birth control, and must have a negative serum beta-human chorionic gonadotropin (beta-hCG) and urine pregnancy test at screening.
- A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control.
- Subjects must have a life expectancy of at least 3 months.
Who cannot join
- Prior treatment with a CD37-targeting agent.
- Prior allogeneic Hematopoietic Stem Cell Transplantation (HSCT).
- Prior treatment with a CD3xCD20 bispecific antibody (Combination Expansion cohort only).
- Autologous HSCT within 3 months before the first dose of GEN3009.
- Lymphomas leukemic phase: high absolute lymphocyte count or the presence of abnormal cells in the peripheral blood indicating circulating lymphoma cells.
- Treatment with an anti-cancer biologic including anti-CD20 therapy, radio-conjugated or toxin-conjugated antibody or chimeric antigen receptor (CAR) T-cell therapy within 4 weeks or 5 half-lives, whichever is shorter, before the first dose of GEN3009. Treatment with small molecules such as BTK inhibitors, BCL2 inhibitors, or PI3K inhibitors within 5 half-lives prior to the first dose of GEN3009.
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- Chemotherapy or radiation therapy within 2 weeks of the first dose of GEN3009.
- Treatment with an investigational drug or an invasive investigational medical device within 4 weeks or 5 half-lives, whichever is shorter, prior to the first dose of GEN3009, and at any time during the study treatment period.
- Autoimmune disease or other diseases that require permanent or high-dose immunosuppressive therapy.
- Received a cumulative dose of corticosteroids more than the equivalent of 250 mg of prednisone within the 2-week period before the first dose of GEN3009.
- Has uncontrolled intercurrent illness.
- Seizure disorder requiring therapy (such as steroids or anti-epileptics) (Combination Expansion cohort only).
- Toxicities from previous anti-cancer therapies have not resolved to baseline levels or to Grade 1 or less except for alopecia and peripheral neuropathy.
- Primary central nervous system (CNS) lymphoma or known CNS involvement at screening.
- Known past or current malignancy other than inclusion diagnosis.
- Had allergic reactions to anti-CD20 or anti-CD37 monoclonal antibody treatment or intolerant to GEN3009 or to the combination therapy excipients.
- Has had major surgery within 4 weeks before screening or will not have fully recovered from surgery, or has major surgery planned during the time the subject is expected to participate in the trial (or within 4 weeks after the last dose of GEN3009 and/or the combination therapy).
- Known history/positive serology for hepatitis B.
- Known medical history or ongoing hepatitis C infection that has not been cured.
- Known history of seropositivity for HIV infection.
- Is a woman who is pregnant or breast-feeding, or who is planning to become pregnant while enrolled in this trial or within 12 months after the last dose of GEN3009 and/or the combination therapy.
- Is a man who plans to father a child while enrolled in this trial or within 12 months after the last dose of GEN3009 and/or the combination therapy.
- Has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments. Additionally, vulnerable subjects or subjects under guardianship, curatorship, judicial protection or deprived of liberty), are excluded from participation in this trial.
- Exposed to live/live attenuated vaccine within 4 weeks prior to initiation of GEN3009 treatment.
- NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Trial locations and contacts
17 sites in 5 countries.
17 sites in 5 countries
United States7 sites
Medical University of South Carolina (MUSC)
Charleston, South Carolina, 29425
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
Ohio State University
Columbus, Ohio, 43210
The University of Texas Southwestern Medical Center
Dallas, Texas, 75390
Colorado Blood Cancer Institute
Denver, Colorado, 80218
MD Anderson Cancer Center
Houston, Texas, 77030
University of Washington - Seattle Cancer Care Alliance
Seattle, Washington, 98133
Spain5 sites
ICO Badalona - Hospital Universitari Germans Trias i Pujol
Badalona, Barcelona, 08916
ICO l'Hospitalet - Hospital Duran i Reynals
Barcelona, L'Hospitalet de Llobregat, 08908
Hospital Universitari Vall d'Hebron
Barcelona, 08035
Hospital Clinic de Barcelona
Barcelona
Hospital Universitario Fundacion Jimenez Diaz
Madrid
Denmark3 sites
Rigshospitalet
Copenhagen
Odense Universitetshospital
Odense
Vejle Sygehus
Vejle
About this study
Official title: Safety and Efficacy of GEN3009 (DuoHexaBody®-CD37) in Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma - A First-in-Human, Open-label, Phase 1/2a Dose Escalation Trial With Dose Expansion Cohorts
The drug that will be investigated in the study is an antibody, GEN3009. Since this is the first study of GEN3009 in humans, the main purpose is to evaluate safety. Besides safety, the study will determine the recommended GEN3009 dose to be tested in a larger group of patients and assess preliminary clinical activity of GEN3009. GEN3009 will be studied in a broad group of cancer patients, having different kinds of lymphomas. All patients will get GEN3009 either as a single treatment (monotherapy) or in combination with another antibody-candidate for treatment of cancer in the blood. The study consists of two parts: Part 1 tests increasing doses of GEN3009 ("escalation"), followed by Part 2 which tests the recommended GEN3009 dose from Part 1 ("expansion").
Read the detailed description
This trial will be conducted in 2 parts: Part 1 (Dose Escalation) and Part 2 (Dose Expansion). All subjects in Part 1 will receive GEN3009, administered at various dose levels in 28-day cycles. Dose Limiting Toxicity (DLT) will be assessed during the first treatment cycle of Part 1 and the Maximum Tolerated Dose (MTD) and/or Recommended phase 2 dose (RP2D) will be identified.
Subjects in Part 2 will be treated with the Part 1-defined RP2D of GEN3009. Some subjects will receive GEN3009 in combination of a fixed dose of another antibody-candidate. Subjects in Part 2 are assigned either to one of 3 groups: Part 2 Monotherapy (hereafter referred to as 'Part 2A'), Part 2 Combination Safety Run-in ('Part2B') or Part 2 Combination ('Part2C').
Various types of B-cell NHLs are studied, including diffuse large B cell lymphoma (DLBCL), high-grade B cell lymphoma (HGBCL), mantle cell lymphoma (MCL), primary mediastinal large B-cell lymphoma (PMBCL), follicular lymphoma (FL), marginal zone lymphoma (MZL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).
- Conditions
- Diffuse Large B-cell Lymphoma, Follicular Lymphoma, Marginal Zone Lymphoma, Small Lymphocytic Lymphoma, Mantle Cell Lymphoma, Chronic Lymphocytic Leukemia
- Being tested
- GEN3009, Epcoritamab
- Keywords
- Anti-CD37, monoclonal antibodies, DuoHexabody®
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse, Lymphoma, Follicular, Lymphoma, B-Cell, Marginal Zone, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Mantle-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GEN3009Biological
Also called DuoHexaBody®-CD37
GEN3009 will be administered by intravenous (IV) infusion in cycles of 28 days
EpcoritamabBiological
Also called DuoBody®-CD3xCD20, GEN3013, EPKINLY™
Epcoritamab will be administered by subcutaneous (SC) injections in cycles of 28 days
| Study group | Role | What they receive |
|---|---|---|
| Monotherapy Arm | Experimental | Not described Receives: Biological: GEN3009 |
| Combination Arm | Experimental | Not described Receives: Biological: GEN3009; Biological: Epcoritamab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Dose Limiting Toxicities (DLTs)
DLTs were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0, except for TLS (Cairo-Bishop grading) and CRS/ICANS (Lee et al., 2019). These criteria include: all Grade 5 toxicities; hematologic events including thrombocytopenia Grade 4, neutropenia Grade 4, Febrile neutropenia Grade 3 or 4, Grade 3 or 4 hemorrhage associated with thrombocytopenia of ≥Grade 3, anemia of Grade 4 and tumor lysis syndrome (TLS) Grade 4; and non-hematologic AEs of Grade 3 or higher excluding certain fevers, hypotension, laboratory values, Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT), nausea, vomiting, diarrhea, fatigue/asthenia, or alopecia (no grading), which meet certain additional criteria.
Measured: During the first treatment cycle (Cycle length=28 days)
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
An AE is any untoward medical occurrence in a clinical trial participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as an AE that meets one of the following criteria: is fatal or life-threatening; results in persistent or significant disability/incapacity; constitutes a congenital anomaly/birth defect; is medically significant (an event that jeopardizes the participant or may require medical or surgical intervention to prevent one of the outcomes listed above [medical and scientific judgment must be exercised in deciding whether an AE is "medically significant"]); required inpatient hospitalization or prolongation of existing hospitalization. TEAEs are defined as AEs which begin, or worsen, during the on-treatment period ending 4 weeks after the last dose of study medication.
Measured: From first dose until 30 days after the last dose (up to 15.5 months)
Number of Participants With AEs of Special Interest (AESI)
AESIs are defined as events (serious or non-serious) that are of scientific and medical concern specific to the sponsor's product or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor may be appropriate.
Measured: From first dose until 30 days after the last dose (up to 15.5 months)
Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs
Laboratory parameters included hematology, serum chemistries and urinalysis. Clinically significant laboratory abnormalities were based upon the Investigator's discretion. Laboratory parameters captured as AEs are reported in this outcome measure.
Measured: From first dose until 30 days after the last dose (up to 15.5 months)
Number of Participants With Clinically Notable Vital Signs
Criteria for clinically notable (elevated and below normal values respectively) vital signs are as follows: Systolic Blood Pressure (SBP): ≥180 millimeters of mercury (mmHg) and an increase ≥20 mmHg from baseline, ≤90 mmHg and a decrease ≥20 mmHg from baseline; Diastolic Blood Pressure (DBP): ≥105 mmHg and an increase ≥15 mmHg from baseline, ≤50 mmHg and a decrease ≥15 mmHg from baseline; Heart rate: ≥120 beats per minute (bpm) with an increase of ≥15 bpm from baseline, ≤50 bpm and a decrease ≥15 bpm from baseline; Temperature: > 38 degree Celsius (°C) and < 35°C. Number of participants with clinically notable elevated and below normal vital signs values up to end of treatment are reported.
Measured: From first dose up to end of treatment (up to 14.5 months)
Number of Participants With Dose Delays and Dose Interruptions
Number of participants with dose delays and dose Interruptions due to AE, Coronavirus disease 2019 (COVID-19), drug administration issues and other unspecified reasons are reported.
Measured: From first dose until 30 days after the last dose (up to 15.5 months)
Actual Dose Intensity
Actual dose intensity (milligrams per cycle [mg/cycle]) is calculated as cumulative dose/number of cycles initiated.
Measured: From first dose until 30 days after the last dose (up to 15.5 months)
Secondary outcomes (16)
Apparent Total Plasma Clearance (CL) of GEN3009
Measured: Pre-dose and 5 minutes post-dose on days 1, 2, 4 (S2 only), 8, 15, 22 and 2 hours (h) and 4h post-dose on days 1 and 2, 24h post-dose on day 2 and 72h post-dose on day 4 of Cycles 1 and 2 (Each cycle length=28 days)
Volume of Distribution of GEN3009
Measured: Pre-dose and 5 minutes post-dose on days 1, 2, 4 (S2 only), 8, 15, 22 and 2h and 4h post-dose on days 1 and 2, 24h post-dose on day 2 and 72h post-dose on day 4 of Cycles 1 and 2 (Each cycle length=28 days)
Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to Day 7 of GEN3009
Measured: Pre-dose and 5 minutes post-dose on days 1, 2 and 4 (S2 only); 2h and 4h post-dose on days 1 and 2, 24h post-dose on day 2 and 72h post-dose on day 4 of Cycles 1 and 2 (Each cycle length=28 days)
AUC From Time 0 to Infinity (AUCinf) of GEN3009
Measured: Pre-dose and 5 minutes post-dose on days 1, 2, 4 (S2 only), 8, 15, 22 and 2h and 4h post-dose on days 1 and 2, 24h post-dose on day 2 and 72h post-dose on day 4 of Cycles 1 and 2 (Each cycle length=28 days)
AUC From Time 0 to Time of Last Dose (AUClast) of GEN3009
Measured: Pre-dose and 5 minutes post-dose on days 1, 2, 4 (S2 only), 8, 15, 22 and 2h and 4h post-dose on days 1 and 2, 24h post-dose on day 2 and 72h post-dose on day 4 of Cycles 1 and 2 (Each cycle length=28 days)
Maximum Observed Plasma Concentration (Cmax) of GEN3009
Measured: Pre-dose and 5 minutes post-dose on days 1, 2, 4 (S2 only), 8, 15, 22 and 2h and 4h post-dose on days 1 and 2, 24h post-dose on day 2 and 72h post-dose on day 4 of Cycles 1 and 2 (Each cycle length=28 days)
Time to Reach Cmax (Tmax) of GEN3009
Measured: Pre-dose and 5 minutes post-dose on days 1, 2, 4 (S2 only), 8, 15, 22 and 2h and 4h post-dose on days 1 and 2, 24h post-dose on day 2 and 72h post-dose on day 4 of Cycles 1 and 2 (Each cycle length=28 days)
Trough Concentrations (Ctrough) of GEN3009
Measured: Pre-dose and 5 minutes post-dose on days 1, 2, 4 (S2 only), 8, 15, 22 and 2h and 4h post-dose on days 1 and 2, 24h post-dose on day 2 and 72h post-dose on day 4 of Cycles 1 and 2 (Each cycle length=28 days)
Terminal Elimination Half-Life (t 1/2) of GEN3009
Measured: Pre-dose and 5 minutes post-dose on days 1, 2, 4 (S2 only), 8, 15, 22 and 2h and 4h post-dose on days 1 and 2, 24h post-dose on day 2 and 72h post-dose on day 4 of Cycles 1 and 2 (Each cycle length=28 days)
Number of Participants With Positive Anti-drug Antibodies (ADAs)
Venous blood samples will be collected for measurement of serum concentrations of ADAs. Number of participants with positive ADAs are reported in this outcome measure. The detection of ADAs was performed using validated, specific and sensitive Electrochemiluminescence Immunoassay (ECLIA) method.
Measured: From first dose until 30 days after the last dose (up to 15.5 months)
Duration of Response (DoR)
DoR is defined as the time from the first documentation of objective tumor response [Complete response (CR) or Partial response (PR)] to the date of first disease progression (PD) or death as assessed by the investigator based on Lugano criteria for B-cell non-Hodgkin lymphoma (B-cell NHL) and International Workshop on Chronic Lymphocytic Leukemia (iwCLL) for chronic lymphocytic leukemia (CLL). Detailed definition of CR, PR and PD as per Lugano and iwCLL criteria in the protocol appendices.
Measured: From date of first documented CR or PR up to disease progression or death (up to approximately 3 years 4 months)
Time to Response (TTR)
TTR: time from first dose of administration until date of first response as assessed by investigator based on Lugano criteria for B-cell NHL and iwCLL for CLL. It is derived for all participants who achieved PR or CR. Detailed definitions of CR, PR and PD as per Lugano and iwCLL criteria in the protocol appendices.
Measured: From date of first documented CR or PR up to disease progression or death (up to approximately 3 years 4 months)
Progression-free Survival (PFS)
PFS is defined as the time in days from Day 1 of Cycle 1 to the day of first documented PD, or the day of death due to any cause, whichever comes first as assessed by investigator based on Lugano Criteria for B-cell NHL and iwCLL for CLL. PFS was estimated using the Kaplan-Meier method. Detailed definitions of PD as per Lugano and iwCLL criteria in the protocol appendices.
Measured: From day of first dose until disease progression or death due to any cause (up to approximately 3 years 4 months)
Overall Survival (OS)
The OS is defined as the time from the start of study treatment until death due to any cause. The OS was estimated using Kaplan-Meier method.
Measured: From day of first dose until disease progression or death due to any cause (up to approximately 3 years 4 months)
Objective Response Rate (ORR)
ORR: the percentage of participants who achieved a best overall response (BOR) of CR or PR as assessed by investigator based on Lugano Criteria for B-cell NHL and iwCLL for CLL. Detailed definitions of CR and PR as per Lugano and iwCLL criteria in the protocol appendices.
Measured: From day of first dose until disease progression or death due to any cause (up to approximately 3 years 4 months)
CR Rate
CR rate was estimated using Clopper-Pearson method. Detailed definitions of CR as per Lugano and iwCLL criteria in the protocol appendices.
Measured: From day of first dose until disease progression or death due to any cause (up to approximately 3 years 4 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2020
- Study start13 Mar 2020
- Primary completion21 Nov 2022
- Study completion28 Jul 2023
Why it stopped: Due to strategic evaluation of GEN3009 within context of Genmab's portfolio, decision not based on any safety or regulatory concerns.
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.
- Other trials for Diffuse Large B-cell LymphomaStudies of the same condition, open and under way.
- More trials run by GenmabThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genmab
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04358458
- Sponsor's protocol ID
- GCT3009-01
- Other IDs
- 2019-002752-16, NL72025.056.20, 2019
- Status last verified
- Oct 2024
- First submitted
- 1 Apr 2020
- Last updated
- 24 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of GEN3009 (DuoHexaBody®-CD37) in Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma - A First-in-Human, Open-label, Phase 1/2a Dose Escalation Trial With Dose Expansion Cohorts
- ClinicalTrials.gov ID
- NCT04358458
- Acronym / sponsor ID
- GCT3009-01
- Conditions
- Diffuse Large B-cell Lymphoma, Follicular Lymphoma, Marginal Zone Lymphoma, Small Lymphocytic Lymphoma, Mantle Cell Lymphoma, Chronic Lymphocytic Leukemia
- Keywords
- Anti-CD37, monoclonal antibodies, DuoHexabody®
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to strategic evaluation of GEN3009 within context of Genmab's portfolio, decision not based on any safety or regulatory concerns.
- Enrolment
- 46 participants (actual)
- Lead sponsor
- GenmabIndustry (pharma, biotech, devices)
- Study start
- 13 Mar 2020 (actual)
- Primary completion
- 21 Nov 2022 (actual)
- Study completion
- 28 Jul 2023 (actual)
- First posted
- 24 Apr 2020 (actual)
- Results
- Posted 13 Aug 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The drug that will be investigated in the study is an antibody, GEN3009. Since this is the first study of GEN3009 in humans, the main purpose is to evaluate safety. Besides safety, the study will determine the recommended GEN3009 dose to be tested in a larger group of patients and assess preliminary clinical activity of GEN3009. GEN3009 will be studied in a broad group of cancer patients, having different kinds of lymphomas. All patients will get GEN3009 either as a single treatment (monotherapy) or in combination with another antibody-candidate for treatment of cancer in the blood. The study consists of two parts: Part 1 tests increasing doses of GEN3009 ("escalation"), followed by Part 2 which tests the recommended GEN3009 dose from Part 1 ("expansion").
Detailed description
This trial will be conducted in 2 parts: Part 1 (Dose Escalation) and Part 2 (Dose Expansion). All subjects in Part 1 will receive GEN3009, administered at various dose levels in 28-day cycles. Dose Limiting Toxicity (DLT) will be assessed during the first treatment cycle of Part 1 and the Maximum Tolerated Dose (MTD) and/or Recommended phase 2 dose (RP2D) will be identified.
Subjects in Part 2 will be treated with the Part 1-defined RP2D of GEN3009. Some subjects will receive GEN3009 in combination of a fixed dose of another antibody-candidate. Subjects in Part 2 are assigned either to one of 3 groups: Part 2 Monotherapy (hereafter referred to as 'Part 2A'), Part 2 Combination Safety Run-in ('Part2B') or Part 2 Combination ('Part2C').
Various types of B-cell NHLs are studied, including diffuse large B cell lymphoma (DLBCL), high-grade B cell lymphoma (HGBCL), mantle cell lymphoma (MCL), primary mediastinal large B-cell lymphoma (PMBCL), follicular lymphoma (FL), marginal zone lymphoma (MZL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Monotherapy Arm | Experimental | Biological: GEN3009 |
| Combination Arm | Experimental | Biological: GEN3009, Biological: Epcoritamab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Be at least 18 years of age.
- Must sign an informed consent form prior to any screening procedures.
- Dose Escalation: Has histologically or cytologically confirmed relapsed and/or refractory B-cell NHL with no available standard therapy or is not a candidate for available standard therapy, and for whom, in the opinion of the investigator, the experimental therapy may be beneficial. All subjects must have received at least two prior lines of systemic therapy.
- Dose Expansion: Has histologically or cytologically confirmed relapsed or refractory B-cell NHL. All subjects must have received at least 2 prior lines of systemic therapy, and,
- Has one of the eligible subtypes of B-cell NHL :
Key exclusion criteria (25 listed)
- Prior treatment with a CD37-targeting agent.
- Prior allogeneic Hematopoietic Stem Cell Transplantation (HSCT).
- Prior treatment with a CD3xCD20 bispecific antibody (Combination Expansion cohort only).
- Autologous HSCT within 3 months before the first dose of GEN3009.
- Lymphomas leukemic phase: high absolute lymphocyte count or the presence of abnormal cells in the peripheral blood indicating circulating lymphoma cells.
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 |
|---|---|---|
| GEN3009Also: DuoHexaBody®-CD37GEN3009 will be administered by intravenous (IV) infusion in cycles of 28 days | Biological | Combination Arm, Monotherapy Arm |
| EpcoritamabAlso: DuoBody®-CD3xCD20, GEN3013, EPKINLY™Epcoritamab will be administered by subcutaneous (SC) injections in cycles of 28 days | Biological | Combination Arm |
Primary outcome
Number of Participants With Dose Limiting Toxicities (DLTs)
Time frame: During the first treatment cycle (Cycle length=28 days)
DLTs were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0, except for TLS (Cairo-Bishop grading) and CRS/ICANS (Lee et al., 2019). These criteria include: all Grade 5 toxicities; hematologic events including thrombocytopenia Grade 4, neutropenia Grade 4, Febrile neutropenia Grade 3 or 4, Grade 3 or 4 hemorrhage associated with thrombocytopenia of ≥Grade 3, anemia of Grade 4 and tumor lysis syndrome (TLS) Grade 4; and non-hematologic AEs of Grade 3 or higher excluding certain fevers, hypotension, laboratory values, Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT), nausea, vomiting, diarrhea, fatigue/asthenia, or alopecia (no grading), which meet certain additional criteria.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
Time frame: From first dose until 30 days after the last dose (up to 15.5 months)
An AE is any untoward medical occurrence in a clinical trial participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as an AE that meets one of the following criteria: is fatal or life-threatening; results in persistent or significant disability/incapacity; constitutes a congenital anomaly/birth defect; is medically significant (an event that jeopardizes the participant or may require medical or surgical intervention to prevent one of the outcomes listed above [medical and scientific judgment must be exercised in deciding whether an AE is "medically significant"]); required inpatient hospitalization or prolongation of existing hospitalization. TEAEs are defined as AEs which begin, or worsen, during the on-treatment period ending 4 weeks after the last dose of study medication.
Number of Participants With AEs of Special Interest (AESI)
Time frame: From first dose until 30 days after the last dose (up to 15.5 months)
AESIs are defined as events (serious or non-serious) that are of scientific and medical concern specific to the sponsor's product or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor may be appropriate.
Number of Participants With Clinically Significant Laboratory Abnormalities Reported as TEAEs
Time frame: From first dose until 30 days after the last dose (up to 15.5 months)
Laboratory parameters included hematology, serum chemistries and urinalysis. Clinically significant laboratory abnormalities were based upon the Investigator's discretion. Laboratory parameters captured as AEs are reported in this outcome measure.
Number of Participants With Clinically Notable Vital Signs
Time frame: From first dose up to end of treatment (up to 14.5 months)
Criteria for clinically notable (elevated and below normal values respectively) vital signs are as follows: Systolic Blood Pressure (SBP): ≥180 millimeters of mercury (mmHg) and an increase ≥20 mmHg from baseline, ≤90 mmHg and a decrease ≥20 mmHg from baseline; Diastolic Blood Pressure (DBP): ≥105 mmHg and an increase ≥15 mmHg from baseline, ≤50 mmHg and a decrease ≥15 mmHg from baseline; Heart rate: ≥120 beats per minute (bpm) with an increase of ≥15 bpm from baseline, ≤50 bpm and a decrease ≥15 bpm from baseline; Temperature: > 38 degree Celsius (°C) and < 35°C. Number of participants with clinically notable elevated and below normal vital signs values up to end of treatment are reported.
Number of Participants With Dose Delays and Dose Interruptions
Time frame: From first dose until 30 days after the last dose (up to 15.5 months)
Number of participants with dose delays and dose Interruptions due to AE, Coronavirus disease 2019 (COVID-19), drug administration issues and other unspecified reasons are reported.
Actual Dose Intensity
Time frame: From first dose until 30 days after the last dose (up to 15.5 months)
Actual dose intensity (milligrams per cycle [mg/cycle]) is calculated as cumulative dose/number of cycles initiated.
16 secondary outcomes
Apparent Total Plasma Clearance (CL) of GEN3009
Time frame: Pre-dose and 5 minutes post-dose on days 1, 2, 4 (S2 only), 8, 15, 22 and 2 hours (h) and 4h post-dose on days 1 and 2, 24h post-dose on day 2 and 72h post-dose on day 4 of Cycles 1 and 2 (Each cycle length=28 days)
Volume of Distribution of GEN3009
Time frame: Pre-dose and 5 minutes post-dose on days 1, 2, 4 (S2 only), 8, 15, 22 and 2h and 4h post-dose on days 1 and 2, 24h post-dose on day 2 and 72h post-dose on day 4 of Cycles 1 and 2 (Each cycle length=28 days)
Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to Day 7 of GEN3009
Time frame: Pre-dose and 5 minutes post-dose on days 1, 2 and 4 (S2 only); 2h and 4h post-dose on days 1 and 2, 24h post-dose on day 2 and 72h post-dose on day 4 of Cycles 1 and 2 (Each cycle length=28 days)
AUC From Time 0 to Infinity (AUCinf) of GEN3009
Time frame: Pre-dose and 5 minutes post-dose on days 1, 2, 4 (S2 only), 8, 15, 22 and 2h and 4h post-dose on days 1 and 2, 24h post-dose on day 2 and 72h post-dose on day 4 of Cycles 1 and 2 (Each cycle length=28 days)
AUC From Time 0 to Time of Last Dose (AUClast) of GEN3009
Time frame: Pre-dose and 5 minutes post-dose on days 1, 2, 4 (S2 only), 8, 15, 22 and 2h and 4h post-dose on days 1 and 2, 24h post-dose on day 2 and 72h post-dose on day 4 of Cycles 1 and 2 (Each cycle length=28 days)
Maximum Observed Plasma Concentration (Cmax) of GEN3009
Time frame: Pre-dose and 5 minutes post-dose on days 1, 2, 4 (S2 only), 8, 15, 22 and 2h and 4h post-dose on days 1 and 2, 24h post-dose on day 2 and 72h post-dose on day 4 of Cycles 1 and 2 (Each cycle length=28 days)
Time to Reach Cmax (Tmax) of GEN3009
Time frame: Pre-dose and 5 minutes post-dose on days 1, 2, 4 (S2 only), 8, 15, 22 and 2h and 4h post-dose on days 1 and 2, 24h post-dose on day 2 and 72h post-dose on day 4 of Cycles 1 and 2 (Each cycle length=28 days)
Trough Concentrations (Ctrough) of GEN3009
Time frame: Pre-dose and 5 minutes post-dose on days 1, 2, 4 (S2 only), 8, 15, 22 and 2h and 4h post-dose on days 1 and 2, 24h post-dose on day 2 and 72h post-dose on day 4 of Cycles 1 and 2 (Each cycle length=28 days)
Terminal Elimination Half-Life (t 1/2) of GEN3009
Time frame: Pre-dose and 5 minutes post-dose on days 1, 2, 4 (S2 only), 8, 15, 22 and 2h and 4h post-dose on days 1 and 2, 24h post-dose on day 2 and 72h post-dose on day 4 of Cycles 1 and 2 (Each cycle length=28 days)
Number of Participants With Positive Anti-drug Antibodies (ADAs)
Time frame: From first dose until 30 days after the last dose (up to 15.5 months)
Duration of Response (DoR)
Time frame: From date of first documented CR or PR up to disease progression or death (up to approximately 3 years 4 months)
Time to Response (TTR)
Time frame: From date of first documented CR or PR up to disease progression or death (up to approximately 3 years 4 months)
Progression-free Survival (PFS)
Time frame: From day of first dose until disease progression or death due to any cause (up to approximately 3 years 4 months)
Overall Survival (OS)
Time frame: From day of first dose until disease progression or death due to any cause (up to approximately 3 years 4 months)
Objective Response Rate (ORR)
Time frame: From day of first dose until disease progression or death due to any cause (up to approximately 3 years 4 months)
CR Rate
Time frame: From day of first dose until disease progression or death due to any cause (up to approximately 3 years 4 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
17 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing GEN3009 and Epcoritamab in people with Diffuse Large B-cell Lymphoma and Follicular Lymphoma, run by Genmab at 17 sites in 5 countries.
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 14 inclusion and 25 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: stopped early, as of the sponsor's last update on 24 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United States, Spain, Denmark, Belgium, Netherlands. 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 13 Aug 2024). 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 Dose Limiting Toxicities (DLTs) (time frame: During the first treatment cycle (Cycle length=28 days)). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 24 Oct 2024.