GEN3014 Safety Trial in Relapsed or Refractory Hematologic Malignancies
Multiple Myeloma (MM), Diffuse Large B Cell Lymphoma (DLBCL), Acute Myeloid Leukemia (AML)
About this trial
This is an interventional treatment trial for Multiple Myeloma (MM) focused on measuring Hexabody®, Anti-CD38, monoclonal antibody
Eligibility Criteria
Inclusion Criteria (Escalation)
- Must be at least 18 years of age.
- Must sign an informed consent form (ICF) prior to any Screening procedures.
- Must have fresh bone marrow samples collected at Screening.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) score 0, 1, or 2.
- Has acceptable laboratory test results during the Screening period
- A woman of reproductive potential must agree to use adequate contraception during the trial and for 12 months after the last GEN3014 administration.
- A woman of childbearing potential must have a negative serum beta-human chorionic gonadotropin (β-hCG) at Screening.
- 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.
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.
- 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.
- 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.
- Potassium level ≥3.0 mEq/L (≥3.0 mmol/L); or corrected serum calcium ≤14.0 mg/dL (≤3.5 mmol/L).
Exclusion Criteria
- Prior treatment with an anti-CD38 antibody except daratumumab or isatuximab.
- Treatment with an anti-cancer agent, chemotherapy, radiation therapy, or major surgery within 2 weeks prior to the first dose of GEN3014.
- Treatment with an investigational drug within 4 weeks or 5 half-lives, whichever is shorter, prior to the first dose of GEN3014.
- Cumulative dose of corticosteroids more than the equivalent of ≥140 mg of prednisone within 2-week period before the first dose of GEN3014.
- Has clinically significant cardiac disease.
- Toxicities from previous anti-cancer therapies have not resolved to baseline levels or to Grade 1 or less except for alopecia and peripheral neuropathy.
- Primary central nervous system (CNS) tumor or known CNS involvement at Screening.
- Has known history/positive serology for hepatitis B
- Known medical history or ongoing hepatitis C infection that has not been cured.
- HIV positive at screening
- Currently receiving any other investigational agents.
- 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.
- A man who plans to father a child while enrolled in this trial or within 12 months after the last dose of GEN3014.
Sites / Locations
- Winship Cancer Institute
- John Theurer Cancer Center
- Levine Cancer Institute
- University Hospitals Cleveland Medical CenterRecruiting
- Medical college of WisconsinRecruiting
- The Alfred HospitalRecruiting
- Royal Prince Alfred HospitalRecruiting
- Fakultni Nemocnice Brno
- Vseobecna fakultni nemocnice
- Fakultni Nemocnice Hradec Kralove FNHKRecruiting
- Fakultni Nemocnice Olomouc (FNOL)
- FNO - Fakultni nemocnice Ostrava
- Aalborg UniversitetRecruiting
- Vejle HospitalRecruiting
- CHRU de Lille
- CHRU de Nantes
- ARENSIA Exploratory Medicine LLCRecruiting
- National & Kapodistrian University of Athens
- University of Athens NKUA
- University General Hospital of Patras
- Ahepa University General hospital
- Dél-Pesti Centrumkórház Országos Hematológiai és Infektológiai Intézet
- Semmelweis Egyetem Belgyógyászati és Hematológiai Klinika
- SzSzB Megyei Egyetemi Oktatokorhaz Josa Andras Oktatokorhaz
- Chonnam National University Hwasun HospitalRecruiting
- Pusan National University Hospital PNUHRecruiting
- Gachon University Gil Medical Center
- Samsung Medical CenterRecruiting
- Seoul National University Hospital
- Institute of Oncology, ARENSIA Exploratory MedicineRecruiting
- Maastricht UMC
- Erasmus MCRecruiting
- UMC Utrecht
- University Centrum KliniczneRecruiting
- Pratia Onkologia KatowiceRecruiting
- Pratia MCMRecruiting
- Wroclaw Medical University
- University of NavarraRecruiting
- University Hospital of SalamancaRecruiting
- Karolinska InstituteRecruiting
- Universitetssjukhuset i LundRecruiting
- Arensia Exploratory MedicineRecruiting
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
GEN3014
Daratumumab
Experimental: GEN3014 Participants in Dose Escalation phase with Relapsed or refractory myeloid myeloma (RRMM) R/R acute myeloid leukemia (AML) Participants in Expansion Part A with RRMM (anti-CD38 mAb-naïve) RRMM (anti-CD38 mAb-refractory) R/R diffuse large B-cell lymphoma (DLBCL) R/R AML Participants in Expansion Part B with • RRMM (anti-CD38 mAb-naïve)
Participants in Expansion Part B with - RRMM (anti-CD38 mAb-naïve)