GEN3014 Trial in Relapsed or Refractory Hematologic Malignancies

NCT04824794 | Terminated Phase 1 DMC FDA Drug

• 4 other identifiers: GCT3014-012020-003781-40NL75422.056.212023-507086-26-00
• Study Type: interventional
• Target: 130
• Locations: 20 countries
• Sites: 52

Brief 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. 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. 2.Expansion Part A will further test the GEN3014 dose determined from the Dose Escalation.
3. 3.Expansion Part B will compare intravenous (IV) GEN3014 with the subcutaneous (SC) daratumumab in ex-US countries.

Conditions

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

Keywords

Hexabody®; Anti-CD38; monoclonal antibody

Outcome Measures

Primary Outcomes (4)

• Dose Escalation: Number of Participants with Dose Limiting Toxicities (DLTs)

  To determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) to be studied in the Expansion part. DLT will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.

  Up to 28 days during the first cycle (cycle =28 days)

• Dose Escalation: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

  From first dose until the end of the safety follow-up period (30 days after last dose; up to 8 years)

• Expansion Part A: Objective Response Rate (ORR) of GEN3014

  ORR is defined as the percentage of participants with a partial response (PR), or better based on International Myeloma Working Group (IMWG) criteria for MM participants, based on Lugano criteria for DLBCL participants, and based on International Working Group (IWG) response criteria for AML participants.

  Up to 8 years

• Expansion Part B: Objective Response Rate (ORR) of GEN3014 IV vs Daratumumab SC in Anti-CD38 mAb-naive RRMM Participants

  ORR is defined as the percentage of participants with a PR, or better based on IMWG criteria.

  Up to 8 years

Secondary Outcomes (32)

• Dose Escalation: Maximum (peak) Plasma Concentration (Cmax) of GEN3014

  Predose and postdose at multiple timepoints up to Cycle 6 (Cycle length=28 days); Pre-dose and 5 minutes post end of infusion from Cycle 7 and beyond (Up to 8 years)

• Dose Escalation: Pre-dose (trough) Concentrations (Ctrough) of GEN3014

  Predose and postdose at multiple timepoints of each Cycle (Cycle length=28 days) (Up to 8 years)

• Dose Escalation: Area Under the Concentration Time Curve From Zero to Last Quantifiable Sample (AUC0-last)

  Predose and postdose at multiple timepoints up to Cycle 6 (Cycle length=28 days); Pre-dose and 5 minutes post end of infusion from Cycle 7 and beyond (Up to 8 years)

• Dose Escalation: Area Under the Concentration Time Curve From Zero to 168 hours (AUC0-168 h)

  Predose and postdose at multiple timepoints up to Cycle 6 (Cycle length=28 days); Pre-dose and 5 minutes post end of infusion from Cycle 7 and beyond (Up to 8 years)

• Dose Escalation: Number of Participants with Anti-Drug Antibody (ADA) of GEN3014

  From first dose until treatment discontinuation (Up to 8 years)

Study Arms (2)

GEN3014

EXPERIMENTAL

Experimental: GEN3014 Participants in Dose Escalation phase with * RRMM * R/R AML Participants in Expansion Part A with * RRMM (anti-CD38 mAb-naïve) * RRMM (anti-CD38 mAb-refractory) * R/R DLBCL * R/R AML Participants in Expansion Part B with • RRMM (anti-CD38 mAb-naïve)

Biological: GEN3014

Daratumumab

ACTIVE COMPARATOR

Participants in Expansion Part B with \- RRMM (anti-CD38 mAb-naïve)

Drug: Daratumumab

Interventions

GEN3014 BIOLOGICAL

GEN3014 is administered by IV infusion.

Also known as: HexaBody®-CD38

GEN3014

Daratumumab DRUG

Daratumumab is administered by SC injections.

Also known as: DARZALEX FASPRO®

Daratumumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must have fresh bone marrow samples collected at Screening for RRMM, R/R AML, and R/R DLBCL with suspected bone marrow involvement.
• 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.
• 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 proteasome inhibitor (PI) and an immunomodulatory imide drug (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.

You may not qualify if:

• Prior treatment with any CD38-directed therapies (eg, daratumumab, isatuximab, CD38 chimeric antigen receptor T cell (CAR-T), bispecific antibody (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.
• Prior allogeneic hematopoietic stem cell transplant (HSCT).
• Autologous HSCT within 3 months of the first dose of GEN3014.

Sponsors & Collaborators

• Genmab: lead

Study Sites (52)

John Theurer Cancer Center

Hackensack, New Jersey, 07601, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Medical college of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Northern Health

Epping, Australia

Location

The Alfred Hospital

Melbourne, Australia

Location

Royal Prince Alfred Hospital

Sydney, Australia

Location

University Clinical Center of the Republic of the Srpska

Banja Luka, Bosnia and Herzegovina

Location

Klinika za hematologiju KCUS

Sarajevo, Bosnia and Herzegovina

Location

UKC - University Clinical Center Tuzla

Tuzla, Bosnia and Herzegovina

Location

Fakultni Nemocnice Brno

Brno, Czechia

Location

Vseobecna fakultni nemocnice

New Town, Czechia

Location

Fakultni Nemocnice Hradec Kralove FNHK

Nový Hradec Králové, Czechia

Location

Fakultni Nemocnice Olomouc (FNOL)

Olomouc, Czechia

Location

FNO - Fakultni nemocnice Ostrava

Poruba, Czechia

Location

Aalborg Universitet

Aalborg, Denmark

Location

Vejle Hospital

Vejle, Denmark

Location

CHRU de Lille

Lille, France

Location

CHRU de Nantes

Nantes, France

Location

ARENSIA Exploratory Medicine LLC

Tbilisi, Georgia

Location

Alexandra General Hospital

Athens, Greece

Location

Evangelismos Hospital NKUA

Athens, Greece

Location

University General Hospital of Patras

Rio, Greece

Location

Ahepa University General hospital

Thessaloniki, Greece

Location

Szabolcs-Szatmar-Bereg County Hospitals and University Hospital, Josa Andras University Hospital

Nyíregyháza, Hungary

Location

Hospital Ampang

Ampang, Malaysia

Location

Hospital Sultanah Aminah

Johor Bahru, Malaysia

Location

Hospital Umum Sarawak

Kuching, Malaysia

Location

Beacon Hospital

Petaling Jaya, Malaysia

Location

Institute of Oncology, ARENSIA Exploratory Medicine

Chisinau, Moldova

Location

Maastricht UMC

Maastricht, Netherlands

Location

Erasmus MC

Rotterdam, Netherlands

Location

UMC Utrecht

Utrecht, Netherlands

Location

Christchurch Hospital

Christchurch, New Zealand

Location

Auckland Cancer Trials Centre

Grafton, New Zealand

Location

Palmerston North Hospital

Palmerston North, New Zealand

Location

North Shore Hospital

Takapuna, New Zealand

Location

University Clinic of Hematology

Skopje, North Macedonia

Location

Makati Medical Center

Makati City, Philippines

Location

University Centrum Kliniczne

Gdansk, Poland

Location

Pratia Onkologia Katowice

Katowice, Poland

Location

Pratia MCM

Krakow, Poland

Location

Wroclaw Medical University

Wroclaw, Poland

Location

Chonnam National University Hwasun Hospital

Gwangju, South Korea

Location

Pusan National University Hospital PNUH

Pusan, South Korea

Location

Gachon University Gil Medical Center

Seongnam, South Korea

Location

Samsung Medical Center

Seoul, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

University of Navarra

Pamplona, Spain

Location

University Hospital of Salamanca

Salamanca, Spain

Location

Karolinska Institute

Huddinge, Sweden

Location

Universitetssjukhuset i Lund

Lund, Sweden

Location

Arensia Exploratory Medicine

Kyiv, Ukraine

Location

MeSH Terms

Conditions

Recurrence; Multiple Myeloma; Lymphoma, Large B-Cell, Diffuse; Leukemia, Myeloid, Acute

Interventions

daratumumab

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Lymphatic Diseases; Leukemia, Myeloid; Leukemia

Study Officials

• Study Official

  Genmab

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose escalation part is sequential while the expansion Part A cohorts are parallel. Expansion Part B is sequential to Expansion Part A RRMM cohort. In Expansion Part B, participants with RRMM are randomized (1:1) to treatment.

Study Record Dates

• First Submitted: March 9, 2021
• First Posted: April 1, 2021
• Study Start: March 9, 2021
• Primary Completion: June 30, 2025
• Study Completion: July 31, 2025
• Last Updated: December 22, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

PH (1); PL (4); GE (1); NO (1); US (3); FR (2); SE (2); MO (1); DK (2); CZ (5); NZ (4); MY (4); KR (5); AU (3); ES (2); UA (1); NL (3); HU (1); GR (4); BO (3)