GEN3014 Safety Trial in Relapsed or Refractory Hematologic Malignancies
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
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
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment GEN3014 |
Biological: GEN3014 (HexaBody®-CD38)
GEN3014 is administered by intravenous (IV) infusion
|
Outcome Measures
Primary Outcome Measures
- Escalation: Dose limiting toxicities (DLTs) [DLTs will be assessed during the first cycle (21 days) in each cohort]
Incidence of DLTs
- Escalation: Adverse events [AEs are collected throughout study until the end of the safety follow-up period (30 days after last dose).]
To assess the safety and tolerability of GEN3014 throughout the treatment period of patients participating in the trial
Secondary Outcome Measures
- Escalation: To establish the pharmacokinetic profile (PK) profile of GEN3014 [Assed throughout trial until the end of the safety follow-up period (30 days after last dose)]]
Maximum concentration of GEN3014 (Cmax) after dosing
- Escalation: To establish the PK profile of GEN3014 [Assed throughout trial until the end of the safety follow-up period (30 days after last dose)]]
Time after dosing at which the maximum drug concentration was observed (Tmax)
- Escalation: To establish the PK profile of GEN3014 [Assed throughout trial until the end of the safety follow-up period (30 days after last dose)]]
Time after dosing at which the lowest drug concentration is observed before the next dose is administered (C_Trough)
- Escalation: To establish the PK profile of GEN3014 [Assed throughout trial until the end of the safety follow-up period (30 days after last dose)]]
Area-under-the-concentration-time curve from zero to last quantifiable sample(AUC_0-C last)
- Escalation: To establish the PK profile of GEN3014 [Assed throughout trial until the end of the safety follow-up period (30 days after last dose)]]
Area-under-the-concentration-time curve from zero to 168 h (AUC_0-168 h)
- Escalation: To establish the PK profile of GEN3014 [Assed throughout trial until the end of the safety follow-up period (30 days after last dose)]]
Accumulation ratios in Cmax (R_A, Cmax)
- Escalation: To establish the PK profile of GEN3014 [Assed throughout trial until the end of the safety follow-up period (30 days after last dose)]]
Accumulation ratios in area-under-the-concentration-time curve (R_A, AUC)
- Escalation: Evaluate immunogenicity of GEN3014 [ADA are collected throughout trial until the end of the safety follow-up period (30 days after last dose)]
Anti-drug antibody response (ADA)
Eligibility Criteria
Criteria
Inclusion Criteria (Escalation)
-
Must be at least 18 years of age.
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Must sign an informed consent form (ICF) prior to any Screening procedures.
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Must have fresh bone marrow samples collected at Screening.
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Eastern Cooperative Oncology Group (ECOG) performance status (PS) score 0, 1, or 2.
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Has acceptable laboratory test results during the Screening period
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A woman of reproductive potential must agree to use adequate contraception during the trial and for 12 months after the last GEN3014 administration.
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A woman of childbearing potential must have a negative serum beta-human chorionic gonadotropin (β-hCG) at Screening.
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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.
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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:
- 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.
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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.
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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.
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Potassium level ≥3.0 mEq/L (≥3.0 mmol/L); or corrected serum calcium ≤14.0 mg/dL (≤3.5 mmol/L).
Exclusion Criteria
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Prior treatment with an anti-CD38 antibody except daratumumab or isatuximab.
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Treatment with an anti-cancer agent, chemotherapy, radiation therapy, or major surgery within 2 weeks prior to the first dose of GEN3014.
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Treatment with an investigational drug within 4 weeks or 5 half-lives, whichever is shorter, prior to the first dose of GEN3014.
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Cumulative dose of corticosteroids more than the equivalent of ≥140 mg of prednisone within 2-week period before the first dose of GEN3014.
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Has clinically significant cardiac disease.
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Toxicities from previous anti-cancer therapies have not resolved to baseline levels or to Grade 1 or less except for alopecia and peripheral neuropathy.
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Primary central nervous system (CNS) tumor or known CNS involvement at Screening.
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Has known history/positive serology for hepatitis B
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Known medical history or ongoing hepatitis C infection that has not been cured.
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HIV positive at screening
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Currently receiving any other investigational agents.
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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.
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A man who plans to father a child while enrolled in this trial or within 12 months after the last dose of GEN3014.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hackensack University Medical Center | Hackensack | New Jersey | United States | 07601-1914 |
| 2 | Levine Cancer Institute | Charlotte | North Carolina | United States | 28204 |
| 3 | Medical college of Wisconsin | Milwaukee | Wisconsin | United States | 53226 |
| 4 | Aalborg Universitet | Aalborg | Denmark | ||
| 5 | Vejle Hospital | Vejle | Denmark | ||
| 6 | University of Navarra | Pamplona | Spain | ||
| 7 | University Hospital of Salamanca | Salamanca | Spain | ||
| 8 | Karolinska Institute | Huddinge | Sweden | ||
| 9 | Universitetssjukhuset i Lund | Lund | Sweden |
Sponsors and Collaborators
- Genmab
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- GCT3014-01