Phase 2 Study of Cevostamab Consolidation Following BCMA CAR T Cell Therapy for Relapsed/Refractory Multiple Myeloma
This is a Phase 2, open-label, single-arm, single stage, single-institution study, with an initial safety run-in period. Potential participants with relapsed/refractory myeloma who are undergoing standard of care, commercially-available BCMA-directed CAR T cell therapy may be identified pre-CAR T cell infusion but are not consented and enrolled until at least 4-6 weeks after CAR T cell infusion, once recovered from acute toxicities. Note: the lymphodepleting chemotherapy and CAR T cell therapy is being administered as part of standard clinical practice and is not considered part of this protocol. Alternative lymphodepleting regimens other than fludarabine and cyclophosphamide (eg in the setting of fludarabine shortages) are acceptable. Cevostamab will be given as an IV infusion once every 3 weeks, starting roughly 10 weeks (day 70 +/- 4 days) post-CAR T cell infusion, with subjects planned to receive 8 cycles initially. Aiming to assess the impact of cevostamab consolidation post-BCMA CAR T cell therapy on rate of MRD-negative complete remission (CR) at 12 months.
• Signed Informed Consent Form(s)
• Age ≥18 years at time of signing Informed Consent Form
• Ability to comply with the study protocol
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Life expectancy of at least 12 weeks
• Participants must have relapsed and/or refractory multiple myeloma with therapy that must include a proteasome inhibitor, immunomodulatory drug (IMiD), and anti-CD38 antibody, and have received a BCMA-directed CAR T cell product as standard of care (i.e. not on a clinical trial) as per the current FDA label, between 6 and 10 weeks prior to enrollment, and have not had progressive disease by IMWG criteria since CAR T cell infusion. Patients who have received out-of-specification CAR T cell products are not eligible.
∙ For patients who received ide-cel, they must have had at least 2 prior lines of therapy prior to ide-cel
‣ For patients who received cilta-cel, they must have had at least 2 prior lines prior to cilta-cel, or 1 prior line and be refractory or intolerant to lenalidomide.
• Agreement to provide bone marrow biopsy and aspirate samples
• Non-hematologic adverse events from prior anti-cancer therapy resolved to Grade ≤ 1, with the certain exceptions.
• Measurable disease is not required for study entry
⁃ Laboratory values as follows:
⁃ a. Hepatic function i. AST and ALT ≤ 3 x ULN ii. Total bilirubin ≤ 1.5 x ULN; b. Hematologic function (cevostamab criteria should be met both at screening (to determine eligibility), as well as on Cycle1, Day 1) i. Platelet count ≥ 50,000/mm3 without transfusion within 7 days prior to first dose ii. ANC ≥ 1000/mm3 iii. Total hemoglobin ≥ 7 g/dL c. Creatinine clearance (CrCl) ≥ 30 mL/min d. Serum calcium (corrected for albumin) level at or below Grade 1 hypercalcemia
⁃ For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, as defined in the protocol.
⁃ For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm, as defined in the protocol.