NCT04824794

GEN3014 Trial in Relapsed or Refractory Hematologic Malignancies

An Open-Label, Multicenter, Phase 1/2 Trial of GEN3014 (HexaBody®-CD38) in Relapsed or Refractory Multiple Myeloma and Other Hematologic Malignancies

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 130 (actual)
• Sponsor: Genmab · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The drug that will be investigated in the study is an antibody, GEN3014. Since this is the first study of GEN3014 in humans, the main purpose is to evaluate safety. In addition to safety, the study will determine the recommended GEN3014 dose to be tested in a larger group of participants and assess preliminary clinical activity of GEN3014. GEN3014 will be studied in relapsed (disease has returned) or refractory (resistant to treatment) multiple myeloma (also known as RRMM) and other blood cancers. The study consists of 3 parts: 1. The Dose Escalation will test increasing doses of GEN3014 to identify a safe dose level to be tested in the other two parts. 2. Expansion Part A will further test the GEN3014 dose determined from the Dose Escalation. 3. Expansion Part B will compare intravenous (IV) GEN3014 with the subcutaneous (SC) daratumumab in ex-US countries. Participants will receive either GEN3014 into the vein or daratumumab under the skin; none will be given placebo. The study duration will be different for the individual participants. Overall, the study may be ongoing up to 5 years after the last participant's first treatment.

Detailed description

This trial will be conducted in 3 parts: Dose Escalation (phase 1), Expansion Parts, A and B (phase 2). In the dose escalation phase GEN3014 will be evaluated in RRMM and relapsed and refractory acute myeloid leukemia (R/R AML). The participants 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. In Expansion Part A, GEN3014 will be further evaluated in 4 cohorts: anti-CD38 monoclonal antibody (mAb)-naive RRMM, anti-CD38 mAb-refractory RRMM, relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL), and R/R AML at the RP2D identified from the Dose Escalation. In 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.

Conditions

• Relapsed or Refractory Multiple Myeloma (RRMM)
• Diffuse Large B Cell Lymphoma (DLBCL)
• Acute Myeloid Leukemia (AML)

Interventions

Type	Name	Description
BIOLOGICAL	GEN3014	GEN3014 is administered by IV infusion.
DRUG	Daratumumab	Daratumumab is administered by SC injections.

Timeline

• Start date: 2021-03-09
• Primary completion: 2025-06-30
• Completion: 2025-07-31
• First posted: 2021-04-01
• Last updated: 2025-12-22

Locations

52 sites across 20 countries: United States, Australia, Bosnia and Herzegovina, Czechia, Denmark, France, Georgia, Greece, Hungary, Malaysia, Moldova, Netherlands, New Zealand, North Macedonia, Philippines, Poland, South Korea, Spain, Sweden, Ukraine

Regulatory

• FDA-regulated drug study