Study of GBR 1342, a CD38/CD3 Bispecific Antibody, in Subjects With Previously Treated Multiple Myeloma

Overview

About this study

The purpose of this study is to determine the safety profile, maximum tolerable dose (MTD) and cohort expansion of single-agent GBR 1342 in subjects with multiple myeloma who have received prior therapies.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Adults with multiple myeloma measurable by IMWG criteria including non-secretory or oligo-secretory multiple myeloma which has relapsed after or is refractory to prior therapies, including proteasome inhibitors (PIs), immunomodulators (IMiDs) and anti-CD38 targeted therapies (daratumumab, isatuximab).
  • Measurable disease defined by at least 1 of the following abnormalities:
    • Serum M-protein ≥ 5 g/L (for IgA ≥ 5 g/L); or
    • Urine light-chain (M-protein) of ≥ 200 mg/24 hours; or 
    • Serum free light chain (sFLC) assay: involved free light chain (FLC) level ≥ 10 mg/dL provided sFLC ratio is abnormal;
    • A biopsy-proven, extramedullary plasmacytoma considered measurable with at least one non-irradiated lesion with a single diameter of ≥ 2 cm;
    • Bone marrow plasma cells > 20% of total bone marrow cells.
  • Adequate hematologic function (if these values are not maintained just before lymphodepletion; discuss with Sponsor), including:
    • Absolute neutrophil count ≥ 1000/mm^3 in the absence of growth factor support (granulocyte colony stimulating factor [G-CSF] within 7 days or pegylated granulocyte colony stimulating factor [peg-G-CSF] within 14 days);
    • Platelet count ≥ 50×10^9 /L in the absence of transfusion support within 7 days prior to obtaining the screening platelet count;
    • Hemoglobin ≥ 7.5 g/dL in the absence of transfusion support (RBC or whole blood within 7 days).
  • Adequate renal function including:
    • Estimated creatinine clearance ≥ 20 mL/min as calculated using the method standard for the institution (in equivocal cases, a 24-hour urine collection can be used to estimate the creatinine clearance more accurately);
    • Serum creatinine ≤2x upper limit of normal (ULN);
    • Not dialysis dependent.
  • Adequate liver function including:
    • Aspartate and alanine aminotransferase (AST and ALT) ≤ 3.5 x upper limit of normal (ULN); ≤ 5.0 x ULN if there is liver involvement by the tumor;
    • Alkaline phosphatase ≤ 3.5 x ULN (≤ 5 x ULN in case of bone metastasis);
    • Total bilirubin ≤ 2.5 x ULN.
  • Age ≥ 18 years at the time of Screening.
  • Eastern Cooperative Oncology Group (ECOG) performance-status score of 2 or less and 1 or less (for France).
  • Life expectancy of at least 3 months (from date of informed consent signing).
  • Recovered from acute effects of any prior therapy or previous surgery and no history of major surgery prior to start of study drug.
    • Note: Recovery is defined as NCI CTCAE v5 Grade ≤1 except for:
    • Adverse events not constituting a safety risk by Investigator judgement;
    • Peripheral neuropathy attributable to bortezomib in the limit of Grade ≤ 2.
  • Willing and able to understand and comply with all aspects of the protocol.
  • Provided written informed consent and any locally required authorization (i.e., Health Insurance Portability and Accountability Act of 1996 [HIPAA]) prior to any protocol-related procedures, including screening evaluations.
  • Women of childbearing potential defined as all women who engage in any heterosexual intercourse and are physiologically capable of becoming pregnant, must have a negative serum pregnancy test result within 7 days prior to first dosing and a negative urine pregnancy test pre-dose on Cycle 1. She must be willing to use a highly effective form of contraception for the duration of the study and for at least 3 months after the last dose of study medication. Highly effective contraception methods include:
    • Use of oral (estrogen and progesterone), injected or implanted hormonal methods of contraception, or other form of hormonal contraception that have comparable efficacy (failure rate < 1%);
    • In case of use of oral contraception, woman should have been stable on the same pill for a minimum of 3 months before taking study treatment;
    • Intrauterine device (IUD);
    • Intrauterine hormone-releasing system (IUS) or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%) for example hormone vaginal ring or transdermal hormone contraception;
    • Female Sterilization (e.g., surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or bilateral tubal ligation at least six weeks before taking investigational drug. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment).
  • Each woman will be considered to be of childbearing potential unless she has been surgically sterilized by total hysterectomy or bilateral tubal ligation/salpingectomy or has been post-menopausal for at least 2 years. For postmenopausal women only, follicle stimulating hormone (FSH) testing will be performed at screening to confirm non-childbearing potential (FSH ≥ 40 IU/L).
  • Men with partners of childbearing potential who engage in any heterosexual intercourse must agree to use condoms in combination with spermicide during the study from the time of informed consent through at least 3 months after the last dose of study drugs. Other highly effective contraception methods include male sterilization (at least 6 months prior to screening).
  • Each man will be considered as able to conceive a child unless surgically sterilized (with appropriate post vasectomy documentation of the absence of sperm in the ejaculate).
  • Seronegative for hepatitis B antigen; positive hepatitis B tests can be further evaluated by confirmatory tests, and if viral load is negative, the subject can be enrolled.
  • Seronegative for hepatitis C antibody; if positive, then further test for presence of antigen by hepatitis C virus polymerase chain reaction (HCV PCR). If HCV antigen tests are negative, then subject can be enrolled.
  • Oxygen saturation level ≥ 92% on room air.
  • Left ventricular ejection fraction (LVEF) ≥ 50% and no pericardial or pleural effusion at Screening.

Exclusion Criteria:

  • Any condition that, in the opinion of the Investigator, would interfere with evaluation of the study drug or interpretation of subject safety or study results.
  • Exposure to daratumumab or isatuximab within 2 months prior to start of study treatment.
  • Active infectious disease considered by the Investigator to be incompatible with the protocol.
  • Evidence of clinically significant cardiovascular and respiratory conditions including myocardial infarction within 1 year, uncontrolled or unstable angina, congestive heart failure (New York Heart Association Class III or IV), arrhythmia (Grade 2 or higher), chronic obstructive pulmonary disease, persistent asthma, or a history of asthma within 5 years.
  • Active central nervous system involvement.
  • Diagnosed with another malignancy that requires active therapy, or active plasma cell leukemia.
  • Subjects not recovered from any therapy-related toxicities from previous chemo-, immuno-, molecular-targeted, biologic, or radiotherapies to at least CTCAE ≤ Grade 1, except in cases of liver metastases, Gilbert’s Syndrome, or alopecia.
  • Anti-myeloma treatment within 2 weeks or autologous stem cell transplantation within 12 weeks of Day 1 of Cycle 1.
  • Use of any investigational drug within the past 4 weeks before start of study drug or concomitantly with this study except for investigational immune-stimulatory therapy (e.g., monoclonal antibodies including checkpoint-regulator targeted treatment [anti-PD-1, anti-PD-L1, anti-CTLA-4, any other “newer” CPIs], bispecific antibodies, CAR-T cells), for which the minimum washout period should be 8 weeks before starting the study drug.
  • Pregnant or breast feeding.
  • Known allergy to any of the ingredients in the formulation (i.e., citrate, sucrose, Tween) or known allergy to any related class of compounds.
  • Known to be seropositive for human immunodeficiency virus (HIV).
  • Has had significant blood loss (> 500 mL) within the last 4 weeks.
  • Subjects requiring prohibited concomitant medications.

Eligibility last updated 1/13/22. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Prashant Kapoor, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available
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CLS-20507130

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