Safety and Efficacy of CS1 CAR-T (WS-CART-CS1) in Subjects With Multiple Myeloma

NCT06185751 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 202404090
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Multiple Myeloma

Keywords

Chimeric Antigen Receptor; CS1

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  From leukaphereis through 24 months after WS-CART-CS1 infusion (approximately 24 months and 1 week)

Secondary Outcomes (5)

• Part A MTD and Part B: Disease-specific objective response rate (ORR)

  Within 3 months of WS-CART-CS1 infusion

• Part A MTD and Part B: Minimal residual disease (MRD) negativity in the marrow

  Week 12

• Part A MTD and Part B: Duration of response (DoR)

  -From response 24 months after WS-CART-CS1 infusion (estimated to be 24 months)

• Part A MTD and Part B: Progression-free survival (PFS)

  From WS-CART-CS1 infusion through completion of follow-up (estimated to be 15 years)

• Part A MTD and Part B: Overall survival (OS)

  From WS-CART-CS1 infusion through completion of follow-up (estimated to be 15 years)

Study Arms (2)

Part A Dose Escalation: WS-CART-CS1

EXPERIMENTAL

* Undergo apheresis procedure for WS-CART-CS1 manufacturing. * Anti-multiple myeloma therapy may be given after leukapheresis and up to one week prior to the start of lymphodepleting chemotherapy at the discretion of the treating physician. * Lymphodepleting chemotherapy on days -5, -4, and -3. * Three days following the last dose of lymphodepleting chemotherapy (on Day 0), WS-CART-CS1 will be infused. * Part A is the dose escalation portion of the study with the starting dose of 0.5 x 10\^6 cells/kg of WS-CART-CS1.

Biological: WS-CART-CS1; Drug: Lymphodepleting chemotherapy

Part B Dose Expansion: WS-CART-CS1

EXPERIMENTAL

* Undergo apheresis procedure for WS-CART-CS1 manufacturing. * Anti-multiple myeloma therapy may be given after leukapheresis and up to one week prior to the start of lymphodepleting chemotherapy at the discretion of the treating physician. * Lymphodepleting chemotherapy on days -5, -4, and -3. * Three days following the last dose of lymphodepleting chemotherapy (on Day 0), WS-CART-CS1 will be infused. * Part B is the dose expansion portion of the study. The dose of WS-CART-CS1 will be determined in Part A of the study.

Biological: WS-CART-CS1; Drug: Lymphodepleting chemotherapy

Interventions

WS-CART-CS1 BIOLOGICAL

-Subject will be hospitalized for 7 days

Part A Dose Escalation: WS-CART-CS1; Part B Dose Expansion: WS-CART-CS1

Lymphodepleting chemotherapy DRUG

* Cyclophosphamide 500 mg/m\^2 IV on Days -5, -4, and -3 * Fludarabine 30 mg/m\^2 IV on Days -5, -4, and -3

Part A Dose Escalation: WS-CART-CS1; Part B Dose Expansion: WS-CART-CS1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Relapsed or refractory multiple myeloma after 3 or more prior lines of therapy, including proteasome inhibitor (e.g. bortezomib or carfilzomib), anti-CD38 therapy (e.g. daratumumab), and anti-BCMA therapies (e.g. BCMA bispecific antibodies or BCMA CAR-T)
• Measurable disease, defined as meeting at least one of the following criteria:
• Serum M-protein ≥ 0.5 g/dL
• Urine M-protein ≥ 200 mg/24 h
• In patients without measurable serum and urine M-protein levels, the difference between involved and uninvolved FLC levels (absolute increase) must be \>10 mg/dL for consideration of defining progression before enrollment
• A biopsy-proven plasmacytoma
• Bone marrow plasma cells \> 30% of total bone marrow cells
• At least 18 years of age.
• ECOG performance status ≤ 1
• Adequate renal, hepatic, respiratory, and cardiovascular function, as defined below:
• Renal function:
• calculated creatinine clearance ≥ 50 mL/min/1.73 m2 OR
• radioisotope glomerular filtration rate ≥ 50 mL/min/1.73 m2 OR
• normal serum creatinine based on age/gender per institutional normal range
• Hepatic function:

You may not qualify if:

• Any prior systemic therapy for multiple myeloma within 14 days before planned day of leukapheresis.
• A history of other malignancy with the exception of treated non-melanomatous skin cancers and malignancies for which all treatment was completed at least 2 years before registration and the subject has no evidence of disease.
• Currently receiving any other investigational agents.
• Receipt of any cellular therapy within 8 weeks prior to the planned start of conditioning.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to CS1 CAR-T or other agents used in the study.
• History of Grade 3 CRS or ICANS with other CAR-Ts (including BCMA CAR).
• Active hepatitis B, active hepatitis C, any uncontrolled infection, or HIV infection.
• Ongoing or active infection or other serious underlying medical condition that would impair the ability to receive protocol treatment.
• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry.

Sponsors & Collaborators

• Paula C. & Rodger O. Riney Blood Cancer Research: collaborator
• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Multiple Myeloma

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Armin Ghobadi, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Armin Ghobadi, M.D.

CONTACT

314-747-2743; arminghobadi@wustl.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2023
• First Posted: December 29, 2023
• Study Start: August 22, 2024
• Primary Completion (Estimated): August 31, 2029
• Study Completion (Estimated): August 31, 2040
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)