MCARH125 / Memorial Sloan-Kettering Cancer Center - LARVOL DELTA

Concurrent Administration of BCMA and GPRC5D Chimeric Antigen Receptor (CAR) T Cells for the Treatment of Relapsed or Refractory Multiple Myeloma: Results from the Phase I TANDEMM Clinical Trial (IMS 2025) - "However, relapses are common and multi-antigen targeting has been proposed as a potential approach to achieve durable responses. We conducted a phase I, dose escalation trial of concurrent infusion of BCMA and GPRC5D CAR T cells, MCARH125 and MCARH109 in patients with relapsed or refractory myeloma. All patients received lymphodepleting chemotherapy with fludarabine and cyclophosphamide followed by CAR T cell infusion at one of 3 dose levels (DL): DL 0, 150 X 106 cells of MCARH125 alone; DL 1, 50 X106 cells of MCARH109 and 150 X 106 cells of MCARH125; DL 2, 150 X106 cells of MCARH109 and 150 X 106 cells of MCARH125... In this proof-of-concept trial, we demonstrate feasibility, safety, and efficacy of concurrently targeting two myeloma specific antigens BCMA and GPRC5D by co-administering two different CAR T products manufactured from a single apheresis."

Clinical • IO biomarker • P1 data • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Inflammation • Multiple Myeloma • CD8

Concurrent administration of BCMA and GPRC5D chimeric antigen receptor (CAR) T cells in advanced multiple myeloma. (PubMed, Blood) - P1 | "We conducted a phase I dose escalation trial of the BCMA CAR T cell therapy MCARH125 alone or in combination with the GPRC5D CAR T cell therapy MCARH109 in patients with heavily pre-treated relapsed or refractory multiple myeloma. The overall response for co-infusion was 78% with a median PFS of 18.2 months. Correlative analysis suggests that antigen loss maybe an important mechanism of resistance even with dual-antigen targeting and we show for the first time that expansion of one CAR population can limit expansion of the second population, as dual-CAR treated patients had significantly less BCMA-CAR expansion than BCMA-CAR alone treated patients, despite equivalent BCMA CAR T cell doses at infusion."

IO biomarker • Journal • CNS Disorders • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Multiple Myeloma • Oncology • GPRC5D

TANDEMM: A Study of MCARH109 and MCARH125 in People With Multiple Myeloma (clinicaltrials.gov) - P1 | N=15 | Active, not recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: Jun 2026 ➔ Jun 2027 | Trial primary completion date: Jun 2026 ➔ Jun 2027

Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology • SDC1

A Study of MCARH109 and MCARH125 in People With Multiple Myeloma (clinicaltrials.gov) - P1 | N=15 | Active, not recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: Jun 2025 ➔ Jun 2026 | Trial primary completion date: Jun 2025 ➔ Jun 2026

Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology • SDC1

A Study of MCARH109 and MCARH125 in People With Multiple Myeloma (clinicaltrials.gov) - P1 | N=15 | Active, not recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Recruiting ➔ Active, not recruiting | N=24 ➔ 15

Enrollment change • Enrollment closed • Hematological Malignancies • Multiple Myeloma • Oncology • SDC1

A Study of MCARH109 and MCARH125 in People With Multiple Myeloma (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: Jun 2024 ➔ Jun 2025 | Trial primary completion date: Jun 2024 ➔ Jun 2025

CAR T-Cell Therapy • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology • SDC1