GEN3014 Safety Trial in Relapsed or Refractory Hematologic Malignancies

• ClinicalTrials.gov Identifier: NCT04824794
• Recruitment Status: Recruiting
• First Posted: April 1, 2021
• Last Update Posted: September 2, 2021
• Sponsor: Genmab
• Information provided by (Responsible Party): Genmab

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
Multiple Myeloma	Biological: GEN3014 (HexaBody®-CD38)	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

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 152 participants
• Allocation: N/A
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Multicenter, Phase 1/2 Trial of GEN3014 (HexaBody®-CD38) in Relapsed or Refractory Multiple Myeloma and Other Hematologic Malignancies
• Actual Study Start Date: March 22, 2021
• Estimated Primary Completion Date: March 2023
• Estimated Study Completion Date: November 2023

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 :

1. Escalation: Dose limiting toxicities (DLTs) [ Time Frame: DLTs will be assessed during the first cycle (21 days) in each cohort ]
   Incidence of DLTs
2. Escalation: Adverse events [ Time Frame: 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 :

1. 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)] ]
   Maximum concentration of GEN3014 (Cmax) after dosing
2. 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)] ]
   Time after dosing at which the maximum drug concentration was observed (Tmax)
3. 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)] ]
   Time after dosing at which the lowest drug concentration is observed before the next dose is administered (C_Trough)
4. 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)] ]
   Area-under-the-concentration-time curve from zero to last quantifiable sample(AUC_0-C last)
5. 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)] ]
   Area-under-the-concentration-time curve from zero to 168 h (AUC_0-168 h)
6. 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)] ]
   Accumulation ratios in Cmax (R_A, Cmax)
7. 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)] ]
   Accumulation ratios in area-under-the-concentration-time curve (R_A, AUC)
8. 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) ]
   Anti-drug antibody response (ADA)

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Contacts

Contact: Genmab A/S Trial Information; +45 70202728; clinicaltrials@genmab.com

Locations

United States, New Jersey

Hackensack University Medical Center; Not yet recruiting

Hackensack, New Jersey, United States, 07601-1914

United States, North Carolina

Levine Cancer Institute; Not yet recruiting

Charlotte, North Carolina, United States, 28204

United States, Wisconsin

Medical college of Wisconsin; Not yet recruiting

Milwaukee, Wisconsin, United States, 53226

Denmark

Aalborg Universitet; Not yet recruiting

Aalborg, Denmark

Vejle Hospital; Recruiting

Vejle, Denmark

Spain

University of Navarra; Not yet recruiting

Pamplona, Spain

University Hospital of Salamanca; Not yet recruiting

Salamanca, Spain

Sweden

Karolinska Institute; Recruiting

Huddinge, Sweden

Universitetssjukhuset i Lund; Not yet recruiting

Lund, Sweden

Sponsors and Collaborators

Genmab

More Information

• Responsible Party: Genmab
• ClinicalTrials.gov Identifier: NCT04824794
• Other Study ID Numbers: GCT3014-01
• First Posted: April 1, 2021
• Last Update Posted: September 2, 2021
• Last Verified: September 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Multiple Myeloma; Neoplasms, Plasma Cell; Hematologic Neoplasms; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Neoplasms by Site