safety and efficacy of bb2121 (ide-cel) combinations in multiple myeloma

Conditions: Multiple Myeloma

Summary: this is a global, open-label, multi-arm, multi-cohort, multi-center, phase 1/2 study to determine the safety, tolerability, efficacy, pk of bb2121 in combination with other therapies in adult subjects with r/rmm. the following combinations will be * arm a will test bb2121 in combination with cc-220 (± low-dose dexamethasone) * arm b will test bb2121 in combination with bms-986405 (jsmd194) combination agents being tested may be administered before, concurrently with and/or following (ie, maintenance) bb2121 infusion. the study will consist of 2 parts: dose finding (phase 1) and dose expansion (phase 2). dose expansion may occur in one or more arms.


Eligibility criteria:
inclusion criteria: participants must satisfy the following criteria to be enrolled in the study: * participant has documented diagnosis of mm and measurable disease, defined as: 1. m-protein (serum protein electrophoresis \[spep ≥ 0.5 g/dl\] or urine protein electrophoresis \[upep\]): upep ≥ 200 mg/24 hours and/or 2. light chain mm without measurable disease in the serum or urine: serum immunoglobulin free light chain ≥ 10 mg/dl (100 mg/l) and abnormal serum immunoglobulin kappa lambda free light chain ratio * participant has received: 1. at least 3 prior mm regimens for arm a cohort 1 and arm b 2. at least 1 but no greater than 3 prior mm regimens for arm a cohort 2 * arm a cohort 1 and arm b: participant has received prior treatment with an immunomodulatory agent, a proteasome inhibitor and an anti-cd38 antibody-containing regimen for at least 2 consecutive cycles. * arm a cohort 2: participant has received prior treatment with an immunomodulatory agent for at least 2 consecutive cycles. * evidence of pd during or within 6 months (measured from the last dose of any drug within the regimen) of completing treatment with the last antimyeloma regimen before study entry. * participant achieved a response (minimal response \[mr\] or better) to at least 1 prior treatment regimen. * participant has an eastern cooperative oncology group (ecog) performance status of 0 or 1. exclusion criteria: the presence of any of the following will exclude a participant from enrollment: * participant has non-secretory mm or has history of or active plasma cell leukemia, waldenstrom's macroglobulinemia, poems syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) or amyloidosis. * participant has any of the following laboratory abnormalities: 1. anc and platelets count as reported below 2. hemoglobin \< 8 g/dl (\< 4.9 mmol/l) (transfusion is not permitted within 21 days of screening) 3. creatinine clearance (crcl) as reported below 4. corrected serum calcium \> 13.5 mg/dl (\> 3.4 mmol/l) 5. serum aspartate aminotransferase (ast) or alanine aminotransferase (alt) \> 2.5 ×upper limit of normal (uln) 6. serum total bilirubin \> 1.5 × uln or \> 3.0 mg/dl for participants with documented gilbert's syndrome 7. international normalized ratio (inr) or activated partial thromboplastin time (aptt) 1.5 × uln, or history of grade ≥ 2 hemorrhage within 30 days, or participant requires ongoing treatment with chronic, therapeutic dosing of anticoagulants (eg, warfarin, low molecular weight heparin, factor xa inhibitors) * participant has inadequate pulmonary function defined as oxygen saturation (sao2) \< 92% on room air. * participant has known chronic obstructive pulmonary disease (copd) with a forced expiratory volume in 1 second (fev1) 50% of predicted normal. * prior exposure to cc-220 (± low-dose dexamethasone) as part of their most recent antimyeloma treatment regimen (arm a). * prior exposure to bms-986405 (jsmd194) (arm b). * previous history of an allogeneic hematopoietic stem cell transplantation, treatment with any gene therapy-based therapeutic for cancer, investigational cellular therapy for cancer or bcma targeted therapy. * treatment arm a cohort 1 and arm b: participant has received autologous stem cell transplantation (asct) within 12 weeks prior to leukapheresis. * treatment arm a cohort 2: participant has received autologous stem cell transplantation (asct) within 12 months prior to leukapheresis.

Keywords: relapsed/refractory multiple myeloma bb2121 ide-cel cc-220 jsmd194 bms-986405 dpd pvd car t karmma-7 phase i phase ii dara pom btz