GEN3014 Trial in Relapsed or Refractory Hematologic Malignancies
- Conditions
- Relapsed or Refractory Multiple Myeloma (RRMM)Diffuse Large B Cell Lymphoma (DLBCL)Acute Myeloid Leukemia (AML)
- Interventions
- Registration Number
- NCT04824794
- Lead Sponsor
- Genmab
- 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. 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 130
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description GEN3014 GEN3014 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) Daratumumab Daratumumab Participants in Expansion Part B with - RRMM (anti-CD38 mAb-naïve)
- Primary Outcome Measures
Name Time Method Dose Escalation: Number of Participants with Dose Limiting Toxicities (DLTs) Up to 28 days during the first cycle (cycle =28 days) 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.
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 Up to 8 years 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.
Expansion Part B: Objective Response Rate (ORR) of GEN3014 IV vs Daratumumab SC in Anti-CD38 mAb-naive RRMM Participants Up to 8 years ORR is defined as the percentage of participants with a PR, or better based on IMWG criteria.
- Secondary Outcome Measures
Name Time Method 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: 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: Accumulation Ratio in Cmax (RA, Cmax) 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: Accumulation Ratio in AUC (RA, AUC) 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) Dose Escalation: Objective Response Rate (ORR) of GEN3014 Up to 8 years ORR is defined as the percentage of participants with a PR or better based on IMWG criteria for MM participants and based on IWG response criteria for AML participants.
Dose Escalation: Time to Reach Cmax (Tmax) 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: Clinical Benefit Rate (CBR) of GEN3014 Up to 8 years CBR was determined by the investigator according to the IMWG response criteria for MM participants.
Dose Escalation: Duration of Response (DOR) of GEN3014 Up to 8 years DOR is defined as time from first response (PR or better) to time of disease progression or death (due to any cause), whichever comes first based on IMWG criteria for MM participants and based on IWG response criteria for AML participants.
Dose Escalation: Time-to-response (TTR) of GEN3014 Up to 8 years TTR is defined as the time from date of first dose to time of response (PR or better) based on IMWG criteria for MM participants and based on IWG response criteria for AML participants.
Dose Escalation: Progression-free survival (PFS) of GEN3014 Up to 8 years PFS is defined as the time from the date of the first dose to the date of progression or death (due to any cause), whichever comes first based on IMWG criteria for MM participants and based on IWG response criteria for AML participants.
Dose Escalation: Overall Survival (OS) of GEN3014 Up to 8 years OS is defined as the time from the date of first dose to the date of death due to any cause.
Expansion Part A: Clinical Benefit Rate (CBR) of GEN3014 Up to 8 years CBR was determined by the investigator according to the IMWG response criteria for MM participants.
Expansion Part A: Duration of Response (DOR) of GEN3014 Up to 8 years DOR is defined as time from first response (PR or better) to time of disease progression or death (due to any cause), whichever comes first based on IMWG criteria for MM participants, based on Lugano criteria for DLBCL participants, and based on IWG response criteria for AML participants.
Expansion Part A: Time-to-response (TTR) of GEN3014 Up to 8 years TTR is defined as the time from date of first dose to time of response (PR or better) for MM participants, based on Lugano criteria for DLBCL participants, and based on IWG response criteria for AML participants.
Expansion Part A: Progression-free survival (PFS) of GEN3014 Up to 8 years PFS is defined as the time from the date of the first dose to the date of progression or death (due to any cause), whichever comes first based on IMWG criteria for MM participants, based on Lugano criteria for DLBCL participants, and based on IWG response criteria for AML participants.
Expansion Part A: Overall Survival (OS) of GEN3014 Up to 8 years OS is defined as the time from the date of first dose to the date of death due to any cause.
Expansion Part A: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) per CTCAE Version 5.0 From first dose until the end of the safety follow-up period (30 days after last dose) (Up to 8 years) Expansion Part A: Number of Participants with Anti-Drug Antibody (ADA) of GEN3014 From first dose until treatment discontinuation (Up to 8 years) Expansion Part A: 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) Expansion Part A: Time to Reach Cmax (Tmax) 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) Expansion Part A: Pre-dose (trough) Concentrations (Ctrough) of GEN3014 Predose and postdose at multiple timepoints of each Cycle (Cycle length=28 days) (Up to 8 years) Expansion Part A: 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) Expansion Part A: 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) Expansion Part A: Accumulation Ratio in Cmax (RA, Cmax) 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) Expansion Part A: Accumulation Ratio in AUC (RA, AUC) 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) Expansion Part A: Accumulation Ratio in Ctrough (RA,Ctrough) 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) Expansion Part B: Ctrough Levels of GEN3014 IV or Daratumumab SC on Cycle 3 Day 1 Cycle 3 Day 1 (cycle = 28 days) Expansion Part B: Very Good Partial Response (VGPR), or better of GEN3014 IV vs Daratumumab SC Up to 8 years Expansion Part B: Complete Response (CR) or better of GEN3014 IV vs Daratumumab SC Up to 8 years Expansion Part B: Duration of Response (DOR) of GEN3014 IV vs Daratumumab SC Up to 8 years DOR is defined as time from first response (PR or better) to time of disease progression or death (due to any cause), whichever comes first based on IMWG criteria for MM participants.
Expansion Part B: Time-to-response (TTR) of GEN3014 IV vs Daratumumab SC Up to 8 years TTR is defined as the time from date of randomization to time of response (PR or better) based on IMWG criteria for MM participants.
Expansion Part B: Progression-free Survival (PFS) of GEN3014 IV vs Daratumumab SC Up to 8 years PFS is defined as the time from date of randomization to the date of progression or death (due to any cause), whichever comes first based on IMWG criteria for MM participants.
Expansion Part B: Overall Survival (OS) of GEN3014 IV vs Daratumumab SC Up to 8 years OS is defined as the time from date of randomization to the date of death due to any cause.
Expansion Part B: Time to Next Therapy (TTNT) Up to 8 years Time to next therapy (TTNT) for participants in the Expansion Part B is defined as the time from date of randomization to the start of subsequent anti-cancer therapy.
Expansion Part B: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) per CTCAE Version 5.0 From first dose until the end of the safety follow-up period (30 days after last dose) (Up to 8 years) Expansion Part B: Number of Participants with Anti-Drug Antibody (ADA) of GEN3014 and Anti-daratumumab Antibodies From first dose until treatment discontinuation (Up to 8 years)
Trial Locations
- Locations (52)
North Shore Hospital
🇳🇿Takapuna, New Zealand
John Theurer Cancer Center
🇺🇸Hackensack, New Jersey, United States
University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
Medical college of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Northern Health
🇦🇺Epping, Australia
The Alfred Hospital
🇦🇺Melbourne, Australia
Royal Prince Alfred Hospital
🇦🇺Sydney, Australia
University Clinical Center of the Republic of the Srpska
🇧🇦Banja Luka, Bosnia and Herzegovina
Klinika za hematologiju KCUS
🇧🇦Sarajevo, Bosnia and Herzegovina
UKC - University Clinical Center Tuzla
🇧🇦Tuzla, Bosnia and Herzegovina
Fakultni Nemocnice Brno
🇨🇿Brno, Czechia
Vseobecna fakultni nemocnice
🇨🇿Nové Město, Czechia
Fakultni Nemocnice Hradec Kralove FNHK
🇨🇿Nový Hradec Králové, Czechia
Fakultni Nemocnice Olomouc (FNOL)
🇨🇿Olomouc, Czechia
FNO - Fakultni nemocnice Ostrava
🇨🇿Poruba, Czechia
Aalborg Universitet
🇩🇰Aalborg, Denmark
Vejle Hospital
🇩🇰Vejle, Denmark
CHRU de Lille
🇫🇷Lille, France
CHRU de Nantes
🇫🇷Nantes, France
ARENSIA Exploratory Medicine LLC
🇬🇪Tbilisi, Georgia
Alexandra General Hospital
🇬🇷Athens, Greece
Evangelismos Hospital NKUA
🇬🇷Athens, Greece
University General Hospital of Patras
🇬🇷Río, Greece
Ahepa University General hospital
🇬🇷Thessaloníki, Greece
Szabolcs-Szatmar-Bereg County Hospitals and University Hospital, Josa Andras University Hospital
🇭🇺Nyíregyháza, Hungary
Chonnam National University Hwasun Hospital
🇰🇷Gwangju, Korea, Republic of
Pusan National University Hospital PNUH
🇰🇷Pusan, Korea, Republic of
Gachon University Gil Medical Center
🇰🇷Seongnam, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Hospital Ampang
🇲🇾Ampang, Malaysia
Hospital Sultanah Aminah
🇲🇾Johor Bahru, Malaysia
Hospital Umum Sarawak
🇲🇾Kuching, Malaysia
Beacon Hospital
🇲🇾Petaling Jaya, Malaysia
Institute of Oncology, ARENSIA Exploratory Medicine
🇲🇩Chisinau, Moldova, Republic of
Maastricht UMC
🇳🇱Maastricht, Netherlands
Erasmus MC
🇳🇱Rotterdam, Netherlands
UMC Utrecht
🇳🇱Utrecht, Netherlands
Christchurch Hospital
🇳🇿Christchurch, New Zealand
Auckland Cancer Trials Centre
🇳🇿Grafton, New Zealand
Palmerston North Hospital
🇳🇿Palmerston North, New Zealand
University Clinic of Hematology
🇲🇰Skopje, North Macedonia
Makati Medical Center
🇵🇭Makati City, Philippines
University Centrum Kliniczne
🇵🇱Gdańsk, Poland
Pratia Onkologia Katowice
🇵🇱Katowice, Poland
Pratia MCM
🇵🇱Kraków, Poland
Wroclaw Medical University
🇵🇱Wrocław, Poland
University of Navarra
🇪🇸Pamplona, Spain
University Hospital of Salamanca
🇪🇸Salamanca, Spain
Karolinska Institute
🇸🇪Huddinge, Sweden
Universitetssjukhuset i Lund
🇸🇪Lund, Sweden
Arensia Exploratory Medicine
🇺🇦Kyiv, Ukraine