An Open-Label, Multicenter, Phase 1/2 Trial of GEN3014 (HexaBody®-CD38) in Relapsed or Refractory Multiple Myeloma and Other Hematologic Malignancies GEN3014 (HEXABODY®-CD38)

What's the purpose of this trial?

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. 

This trial is currently open and accepting patients.


What will happen during the trial?

This trial will be conducted in 3 parts: Dose Escalation (phase 1), Expansion Parts, A and B (phase 2).

In the dose escalation phase GEN314 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 per protocol. 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.

You may be able to join this trial if you:

The following criteria is a partial list of reasons why patients may be eligible to participate in this clinical trial. Further evaluation with a medical professional is required.

Key Inclusion Criteria

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.

Specific for AML:
13. Relapsed or refractory AML, both de novo or secondary; must have failed all conventional therapy. Acute promyelocytic leukemia (APL) is excluded from this trial. Note: Relapse is defined by BM blasts ≥5% in patients who have been in CR previously, or reappearance of blasts in the blood, or development of extramedullary AML. Refractory is defined as not being able to achieve a CR after the initial therapy.
14. Subject with relapsed AML who received at least 2 prior therapies for AML with the exception of hydroxyurea.
15. •Subject with refractory AML who received at least 1 prior line of therapy for AML with the exception of hydroxyurea.
16. Subject's life expectancy at Screening is judged to be at least 3 months.

Specific for DLBCL
17. Relapsed or refractory DLBCL, both de novo or histologically transformed. Note: Relapsed disease is defined as the reappearance or growth of lymphoma after at least 6 months duration of response. Refractory disease is defined as failure to achieve response after at least 2 cycles of therapy or reappearance after a duration of response of \<6 months. Subjects with R/R DLBCL must have exhausted standard therapies, at the investigator's discretion.
18. Received at least 2 prior lines of systemic therapy, with 1 being a CD20-containing chemoimmunotherapy.
19. Have at least 1 measurable site of disease:

* A fluorodeoxyglucose (FDG)-positron emission tomography (PET) computed tomography (CT) scan demonstrating positive lesion compatible with CT (or magnetic resonance imaging \[MRI\])-defined anatomical tumor sites And
* A CT scan (or MRI) with involvement of ≥2 clearly-demarcated lesions/nodes with long axis \>1.5 cm and short axis \>1.0 cm; or 1 clearly-demarcated lesion/node with a long axis \>2.0 cm and a short axis ≥1.0 cm.
20. Must have available archival or fresh tumor tissue or both to submit to a central laboratory for CD38 assay

Key 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 study treatment.
3. Treatment with an investigational drug within 4 weeks or 5 half-lives, whichever is shorter, prior to the first dose of study treatment.
4. Cumulative dose of corticosteroids more than the equivalent of ≥140 mg of prednisone within 2-week period before the first dose of study treatment.
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 study treatment.
13. A man who plans to father a child while enrolled in this trial or within 12 months after the last dose of study treatment.

Specific Exclusion Criteria for RRMM:
14. • Prior allogeneic HSCT.
15. Autologous HSCT within 3 months of the first dose of GEN3014.

Specific Exclusion Criteria for R/R AML:
16. • \<5% blasts in blood or bone marrow at Screening.
17. • Prior autologous HSCT.
18. • Allogenic HSCT within 3 months of the first dose of GEN3014.
19. • Active graft-versus-host-disease requiring immunosuppressive treatment. Any immunosuppressive medication (eg, calcineurin inhibitors) must be stopped ≥4 weeks prior to the first dose of GEN3014.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Additional Trial Information

Phase 1/2

Enrollment: 252 patients (estimated)

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Published Results

Preliminary Dose-Escalation Results from a Phase 1/2 Study of GEN3014 (HexaBody®-CD38) in Patients (pts) with Relapsed or Refractory Multiple Myeloma (RRMM)

July 10, 2022

As of July 10, 2022, 24 pts with RRMM were treated (median age, 65 y; range, 45–84). Pts were heavily pretreated with a median of 7 prior lines of Tx (range, 3–13). Most pts (67%) had prior exposure to a daratumumab- or isatuximab-containing regimen, with 8 pts naive to anti-CD38 mAb. GEN3014 was well tolerated; the most common Tx-emergent AEs were infusion-related reactions (IRRs; 75.0%), neutropenia (62.5%), anemia (33.3%), diarrhea (33.3%), pyrexia (25.0%), and thrombocytopenia (25.0%). IRRs were mostly low grade (G; 62.5% G1–2, 12.5% G3, no G4), occurred mainly during the first infusion, and were manageable. There were no Tx-related deaths or dose-limiting toxicities observed at doses up to 16 mg/kg, the RP2D. Disease progression led to discontinuation in 80% of pts. Among 19 response-evaluable pts (5 naive to anti-CD38 mAb, 14 refractory to anti-CD38 mAb), preliminary antitumor activity was seen. In pts naive to anti-CD38 mAb, 2 pts achieved very good partial response (1 each at 4 and 24 mg/kg); 1 achieved minimal response (MR; 16 mg/kg). In pts refractory to anti-CD38 mAb, 2 pts achieved MR (1 each at 8 and 16 mg/kg). Five pts remained on Tx (4 naive and 1 refractory to anti-CD38 mAb). Updated data will be presented.

Trial Locations

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New Jersey

Wisconsin

Medical College of Wisconsin Froedtert Hospital

Milwaukee, WI

Open and Accepting
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