Phase 1 Dose-Escalation and Dose-Expansion Study of the Safety and Efficacy of CS1 CAR-T (WS-CART-CS1) in Subjects With Multiple Myeloma
Summary
Despite recent therapeutic advances, multiple myeloma (MM) remains an incurable disease. Although survival has improved, there are nevertheless diminishing durations of response to each subsequent line of therapy. This highlights the need for further therapeutic innovation. BCMA-targeting CAR-T cells show impressive response rates; however, their median duration of response is disappointing. The investigators propose that CS1(SLAMF7)-targeting CAR-T cells will fill a gap in the MM armamentarium. CS1 is an attractive target in MM because it is expressed in most patients. Elotuzumab (Empliciti®), an approved anti-CS1 antibody, has proven the clinical efficacy of this target. CAR-T cells are an ideal modality to target CS1, given that two approved treatments, ide-cel (idecabtagene vicleucel, AbecmaTM) and cilta-cel (ciltacabtagene autoleucel, Carvykti™), have proven the potential for cellular immunotherapy in MM. The investigators are testing the safety and preliminary anti-myeloma efficacy of WS-CART-CS1, a CAR-T cell therapy targeting CS1.
Arms & interventions
- BiologicalWS-CART-CS1
-Subject will be hospitalized for 7 days
- DrugLymphodepleting chemotherapy
* Cyclophosphamide 500 mg/m\^2 IV on Days -5, -4, and -3 * Fludarabine 30 mg/m\^2 IV on Days -5, -4, and -3
Outcome measures
Primary
Part A: Frequency and severity of treatment-emergent adverse events
* Graded by CTCAE v 5.0. * Adverse events will be tracked at the time of leukapheresis through 28 days post leukapheresis, to capture any AEs related to leukapheresis only. * Adverse events will then be collected beginning with lymphodepletion chemotherapy and continue through Day 100 post WS-CART-CS1 infusion or until initiation of another anticancer therapy, whichever occurs first. * After Day 100, only targeted AEs will be reported through 24 months after WS-CART-CS1 infusion or until disease progression or relapse, whichever occurs first. Targeted AEs include and are limited to secondary malignancies, CRS, ICANS, prolonged cytopenia (defined as Grade 3 neutropenia or thrombocytopenia lasting more than 28 days after WS-CART-CS1 infusion), and SAEs or SUSARs that are not attributable to progressive disease or extraneous causes.
Time frame: From leukapheresis through 24 months after WS-CART-CS1 infusion (approximately 24 months and 1 week)
Part A: Frequency of dose-limiting toxicities (DLTs)
DLTs are defined in the protocol.
Time frame: From WS-CART-CS1 infusion through 28 days
Part B: Frequency and severity of treatment-emergent adverse events
* Graded by CTCAE v 5.0. * Adverse events will be tracked at the time of leukapheresis through 28 days post leukapheresis, to capture any AEs related to leukapheresis only. * Adverse events will then be collected beginning with lymphodepletion chemotherapy and continue through Day 100 post WS-CART-CS1 infusion or until initiation of another anticancer therapy, whichever occurs first. * After Day 100, only targeted AEs will be reported through 24 months after WS-CART-CS1 infusion or until disease progression or relapse, whichever occurs first. Targeted AEs include and are limited to secondary malignancies, CRS, ICANS, prolonged cytopenia (defined as Grade 3 neutropenia or thrombocytopenia lasting more than 28 days after WS-CART-CS1 infusion), and SAEs or SUSARs that are not attributable to progressive disease or extraneous causes.
Time frame: From leukaphereis through 24 months after WS-CART-CS1 infusion (approximately 24 months and 1 week)
Secondary
Part A MTD and Part B: Disease-specific objective response rate (ORR)
Time frame: Within 3 months of WS-CART-CS1 infusion
Part A MTD and Part B: Minimal residual disease (MRD) negativity in the marrow
Time frame: Week 12
Part A MTD and Part B: Duration of response (DoR)
Time frame: -From response 24 months after WS-CART-CS1 infusion (estimated to be 24 months)
Part A MTD and Part B: Progression-free survival (PFS)
Time frame: From WS-CART-CS1 infusion through completion of follow-up (estimated to be 15 years)
Part A MTD and Part B: Overall survival (OS)
Time frame: From WS-CART-CS1 infusion through completion of follow-up (estimated to be 15 years)
Eligibility criteria
Study locations (1)
Washington University School of Medicine
St Louis, Missouri, 63110