Multiple Myeloma Clinical Trial
GEN3014 Safety Trial in Relapsed or Refractory Hematologic Malignancies
This trial is an open-label, safety trial of GEN3014 (HexaBodyÂ®-CD38). The trial consists of two parts: a dose escalation part phase 1, first-in-human (FIH), and an expansion part phase 2a.
This trial will be conducted in 3 parts: Dose Escalation (phase 1), Expansion Parts, A and B (phase 2).
All participants in the Dose Escalation, GEN3014 will be evaluated in RRMM and R/R AML, will receive GEN3014, administered at various dose levels in 28-day cycles. Dose Limiting Toxicities (DLTs) will be assessed during the first treatment cycle and the Maximum Tolerated Dose (MTD) and/or Recommended phase 2 dose (RP2D) will be determined.
Expansion Part A, GEN3014 will be further evaluated in 4 cohorts: anti-CD38 mAb-naive RRMM, anti-CD38 mAb-refractory RRMM, R/R DLBCL, and R/R AML at the RP2D identified from the Dose Escalation per protocol. Expansion Part B, GEN3014 IV will be compared to daratumumab SC, head-to-head (H2H) to evaluate whether GEN3014 may be more potent in anti-CD38 mAb-naïve RRMM participants.
Key Inclusion Criteria
Must have fresh bone marrow samples collected at Screening.
Dose Escalation phase, Expansion part A (for MM and AML) and Expansion part B- Eastern Cooperative Oncology Group (ECOG) performance status (PS) score 0, 1, or 2. Expansion part A (for DLBCL): ECOG PS 0 or 1.
Expansion part A - Has acceptable laboratory test results during the Screening period.
A woman of reproductive potential must agree to use adequate contraception during the trial and for 12 months after the last GEN3014 or daratumumab SC administration.
A woman of childbearing potential must have a negative serum beta-human chorionic gonadotropin (β-hCG) at Screening and additionally, for Expansion Part B, within 72 hours of the first dose of study treatment prior to dosing.
A woman must agree not to donate eggs (ova, oocytes) for assisted reproduction during the trial and for 12 months after receiving the last dose of GEN3014 or daratumumab SC.
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 and all men must not donate sperm during the trial and for 12 months after receiving the last dose of GEN3014 or daratumumab SC.
Specific for RRMM:
Must have documented multiple myeloma as defined by the criteria below and have evidence of disease progression on the most recent prior treatment regimen based on IMWG criteria:
Prior documentation of monoclonal plasma cells in the bone marrow ≥10% or presence of a biopsy-proven plasmacytoma and,
Measurable disease at baseline as defined by any of the following:
Immunoglobulin (Ig) G, IgA, IgD, or IgM myeloma: Serum M-protein level ≥0.5 g/dL (≥5 g/L) or urine M protein level ≥200 mg/24 hours or,
Light chain myeloma: Serum Ig free light chain (FLC) ≥10 mg/dL and abnormal serum Ig kappa lambda FLC ratio.
Note: Participants with RRMM must have exhausted standard therapies, at the investigator's discretion.
For anti-CD38 mAb-naive RRMM Cohort: Participant received at least 3 prior lines of therapy including a PI and an IMiD in any order, or is double refractory to a PI and an IMiD; or participant received ≥ 2 prior lines of therapy if 1 of those lines included a combination of PI and IMiD. Note: Participants should not have received any anti-CD38 antibody.
Anti-CD38 mAb-naive RRMM subjects will be enrolled from ex-US countries
Dose Escalation phase - For anti-CD38 mAb-treated RRMM Cohort: Participant has received at least 2 prior lines of therapy and must have discontinued daratumumab or relapsed-multiple-myeloma/" >isatuximab for at least 4 weeks prior to the first dose of GEN3014. Note: Participants should not have received any other anti-CD38 antibody except daratumumab or isatuximab.
Specific for R/R AML:
Relapsed or refractory AML, both de novo or secondary; must have failed all conventional therapy. Acute promyelocytic leukemia (APL) is excluded from this trial.
Participant with relapsed AML who received at least 2 prior therapies for AML with the exception of hydroxyurea.
Participant with refractory AML who received at least 1 prior line of therapy for AML with the exception of hydroxyurea.
Participant's life expectancy at Screening is judged to be at least 3 months.
Specific for DLBCL:
Expansion phase: Relapsed or refractory DLBCL, both de novo or histologically transformed. Participants with R/R DLBCL must have exhausted standard therapies, at the investigator's discretion.
Expansion phase: Received at least 2 prior lines of systemic therapy, with 1 being a CD20-containing chemoimmunotherapy.
Expansion phase: Have at least 1 measurable site of disease as per Lugano criteria.
Expansion phase: Must have available archival or fresh tumor tissue or both to submit to a central laboratory for CD38 assay.
Key Exclusion Criteria
Prior treatment with any CD38-directed therapies (eg, daratumumab, isatuximab, CD38 CAR-T, bispecific Ab) in anti-CD38 mAb-naive RRMM Cohort. Note: Prior daratumumab or isatuximab exposure is allowed for anti-CD38 mAb-treated RRMM participants in the Dose Escalation and anti-CD38 mAb-refractory RRMM Cohort in the Expansion Part A.
Treatment with an anti-cancer agent, chemotherapy, radiation therapy, or major surgery within 2 weeks prior to the first dose of study treatment (Dose Escalation and Expansion Part A) or randomization (Expansion Part B).
Treatment with an investigational drug within 4 weeks or 5 half-lives, whichever is shorter, prior to the first dose of study treatment (Dose Escalation and Expansion Part A) or randomization (Expansion Part B).
Cumulative dose of corticosteroids more than the equivalent of ≥140 mg of prednisone within 2-week period before the first dose of study treatment (Dose Escalation and Expansion Part A) or maximum cumulative dose of dexamethasone 160 mg within 28 days of randomization (Expansion Part B).
Has clinically significant cardiac disease.
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) tumor or known CNS involvement at Screening.
Has known history/positive serology for hepatitis B.
Known medical history or ongoing hepatitis C infection that has not been cured.
Known history of seropositivity of human immunodeficiency virus (HIV) (Dose Escalation and Expansion Part A) or to be positive for HIV with details in the protocol (Expansion Part B).
Currently receiving any other investigational agents.
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 study treatment.
A man who plans to father a child while enrolled in this trial or within 12 months after the last dose of study treatment.
Specific Exclusion Criteria for RRMM:
Prior allogeneic hematopoietic stem cell transplant (HSCT).
Autologous HSCT within 3 months of the first dose of GEN3014.
Specific Exclusion Criteria for R/R AML:
<5% blasts in blood or bone marrow at Screening.
Prior autologous HSCT.
Allogenic HSCT within 3 months of the first dose of GEN3014.
Active graft-versus-host-disease requiring immunosuppressive treatment. Any immunosuppressive medication (eg, calcineurin inhibitors) must be stopped ≥4 weeks prior to the first dose of GEN3014.
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
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There are 5 Locations for this study
Atlanta Georgia, 30322, United States
Hackensack New Jersey, 07601, United States
Charlotte North Carolina, 28150, United States
Cleveland Ohio, 44106, United States
Milwaukee Wisconsin, 53226, United States
Melbourne , , Australia
Sydney , , Australia
Brno , , Czechia
Nové Město , , Czechia
Nový Hradec Králové , , Czechia
Olomouc , , Czechia
Poruba , , Czechia
Aalborg , , Denmark
Vejle , , Denmark
Lille , , France
Nantes , , France
Tbilisi , , Georgia
Athens , , Greece
Athens , , Greece
Río , , Greece
Thessaloníki , , Greece
Budapest , , Hungary
Budapest , , Hungary
Nyíregyháza , , Hungary
Gwangju , , Korea, Republic of
Pusan , , Korea, Republic of
Seongnam , , Korea, Republic of
Seoul , , Korea, Republic of
Seoul , , Korea, Republic of
Chisinau , , Moldova, Republic of
Maastricht , , Netherlands
Rotterdam , , Netherlands
Utrecht , , Netherlands
Gdańsk , , Poland
Katowice , , Poland
Kraków , , Poland
Wrocław , , Poland
Pamplona , , Spain
Salamanca , , Spain
Huddinge , , Sweden
Lund , , Sweden
Kyiv , , Ukraine
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