Description:
This trial is an open-label, safety trial of GEN3014 (HexaBody®-CD38). The trial consists of
two parts: a dose escalation part phase 1, first-in-human (FIH), and an expansion part phase
2a.
Title
- Brief Title: GEN3014 Safety Trial in Relapsed or Refractory Hematologic Malignancies
- Official Title: An Open-Label, Multicenter, Phase 1/2 Trial of GEN3014 (HexaBody®-CD38) in Relapsed or Refractory Multiple Myeloma and Other Hematologic Malignancies
Clinical Trial IDs
- ORG STUDY ID:
GCT3014-01
- NCT ID:
NCT04824794
Conditions
Interventions
Drug | Synonyms | Arms |
---|
GEN3014 (HexaBody®-CD38) | | Treatment |
Purpose
This trial is an open-label, safety trial of GEN3014 (HexaBody®-CD38). The trial consists of
two parts: a dose escalation part phase 1, first-in-human (FIH), and an expansion part phase
2a.
Detailed Description
The purpose of the escalation part of the trial is to determine the maximum tolerated dose
(MTD) and the recommended phase 2 dose (RP2D), as well as to establish the safety profile of
GEN3014 (HexaBody®-CD38) in Relapsed or Refractory Multiple Myeloma and Other Hematologic
Malignancies
Trial Arms
Name | Type | Description | Interventions |
---|
Treatment | Experimental | GEN3014 | |
Eligibility Criteria
Inclusion Criteria (Escalation)
1. Must be at least 18 years of age.
2. Must sign an informed consent form (ICF) prior to any Screening procedures.
3. Must have fresh bone marrow samples collected at Screening.
4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) score 0, 1, or 2.
5. Has acceptable laboratory test results during the Screening period
6. A woman of reproductive potential must agree to use adequate contraception during the
trial and for 12 months after the last GEN3014 administration.
7. A woman of childbearing potential must have a negative serum beta-human chorionic
gonadotropin (β-hCG) at Screening.
8. 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.
9. 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.
Specific for RRMM:
10. 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:
- IgG, 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: Subjects with RRMM must have exhausted standard therapies, at the investigator's
discretion.
11. For anti-CD38 mAb-naive RRMM Cohort: Subject 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 subject received ≥ 2 prior lines of therapy if 1 of those lines included a
combination of PI and IMiD. Note: Subjects should not have received any anti-CD38
antibody. Anti-CD38 mAb naive RRMM subjects will be recruited from countries where
anti-CD38 therapies are not available.
12. For anti-CD38 mAb-treated RRMM Cohort: Subject has received at least 2 prior lines of
therapy and must have discontinued daratumumab or isatuximab for at least 4 weeks
prior to the first dose of GEN3014. Note: Subjects should not have received any other
anti-CD38 antibody except daratumumab or isatuximab.
13. Potassium level ≥3.0 mEq/L (≥3.0 mmol/L); or corrected serum calcium ≤14.0 mg/dL (≤3.5
mmol/L).
Exclusion Criteria
1. Prior treatment with an anti-CD38 antibody except daratumumab or isatuximab.
2. Treatment with an anti-cancer agent, chemotherapy, radiation therapy, or major surgery
within 2 weeks prior to the first dose of GEN3014.
3. Treatment with an investigational drug within 4 weeks or 5 half-lives, whichever is
shorter, prior to the first dose of GEN3014.
4. Cumulative dose of corticosteroids more than the equivalent of ≥140 mg of prednisone
within 2-week period before the first dose of GEN3014.
5. Has clinically significant cardiac disease.
6. Toxicities from previous anti-cancer therapies have not resolved to baseline levels or
to Grade 1 or less except for alopecia and peripheral neuropathy.
7. Primary central nervous system (CNS) tumor or known CNS involvement at Screening.
8. Has known history/positive serology for hepatitis B
9. Known medical history or ongoing hepatitis C infection that has not been cured.
10. HIV positive at screening
11. Currently receiving any other investigational agents.
12. 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 GEN3014.
13. A man who plans to father a child while enrolled in this trial or within 12 months
after the last dose of GEN3014.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Escalation: Dose limiting toxicities (DLTs) |
Time Frame: | DLTs will be assessed during the first cycle (21 days) in each cohort |
Safety Issue: | |
Description: | Incidence of DLTs |
Secondary Outcome Measures
Measure: | Escalation: To establish the pharmacokinetic profile (PK) profile of GEN3014 |
Time Frame: | Assed throughout trial until the end of the safety follow-up period (30 days after last dose)] |
Safety Issue: | |
Description: | Maximum concentration of GEN3014 (Cmax) after dosing |
Measure: | Escalation: To establish the PK profile of GEN3014 |
Time Frame: | Assed throughout trial until the end of the safety follow-up period (30 days after last dose)] |
Safety Issue: | |
Description: | Time after dosing at which the maximum drug concentration was observed (Tmax) |
Measure: | Escalation: To establish the PK profile of GEN3014 |
Time Frame: | Assed throughout trial until the end of the safety follow-up period (30 days after last dose)] |
Safety Issue: | |
Description: | Time after dosing at which the lowest drug concentration is observed before the next dose is administered (C_Trough) |
Measure: | Escalation: To establish the PK profile of GEN3014 |
Time Frame: | Assed throughout trial until the end of the safety follow-up period (30 days after last dose)] |
Safety Issue: | |
Description: | Area-under-the-concentration-time curve from zero to last quantifiable sample(AUC_0-C last) |
Measure: | Escalation: To establish the PK profile of GEN3014 |
Time Frame: | Assed throughout trial until the end of the safety follow-up period (30 days after last dose)] |
Safety Issue: | |
Description: | Area-under-the-concentration-time curve from zero to 168 h (AUC_0-168 h) |
Measure: | Escalation: To establish the PK profile of GEN3014 |
Time Frame: | Assed throughout trial until the end of the safety follow-up period (30 days after last dose)] |
Safety Issue: | |
Description: | Accumulation ratios in Cmax (R_A, Cmax) |
Measure: | Escalation: To establish the PK profile of GEN3014 |
Time Frame: | Assed throughout trial until the end of the safety follow-up period (30 days after last dose)] |
Safety Issue: | |
Description: | Accumulation ratios in area-under-the-concentration-time curve (R_A, AUC) |
Measure: | Escalation: Evaluate immunogenicity of GEN3014 |
Time Frame: | ADA are collected throughout trial until the end of the safety follow-up period (30 days after last dose) |
Safety Issue: | |
Description: | Anti-drug antibody response (ADA) |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Genmab |
Last Updated
April 1, 2021