CAR-T shows ‘impressive efficacy’ for patients with advanced multiple myeloma

CHICAGO — A novel chimeric antigen receptor T-cell therapy has elicited objective responses among the first eight patients who received the treatment, according to results from the phase 1 POLARIS trial presented at ASCO Annual Meeting.

Use of OriCAR-017 (Oricell Therapeutics) — an autologous, gene edited, GPRC5D-directed CAR T-cell therapy — resulted in a manageable safety profile and “impressive efficacy in [patients with] relapsed or refractory multiple myeloma,” He Huang, MD, PhD, and colleagues of Zhejiang University School of Medicine in China, wrote.

Background

OriCAR-017 is a second-generation CAR T-cell therapy targeting GPRC5D, a G protein-coupled receptor.

“Therapies using newer targets are urgently needed for patients with relapsed or refractory multiple myeloma, especially for those who have relapsed after [B-cell maturation antigen]-targeted therapy,” Huang said during a presentation. “GPRC5D is a surface receptor with high and selective expression on myeloma cells, whereas its expression on normal tissues is limited to hard keratinized tissues, such as hair follicles and nail matrix.”

Methodology

POLARIS is single-center dose-escalation trial that has enrolled 12 adults with relapsed or refractory multiple myeloma who have confirmed expression of GPRC5D in bone marrow plasma cells or tumor tissue. Patients who received prior B-cell maturation antigen (BCMA)-targeted therapy could enroll in the study.

Study participants underwent lymphodepleting chemotherapy followed by a single infusion of OriCAR-017 at one of three dose levels: 1 × 10⁶ cells/kg, 3 × 10⁶ cells/kg or 6 × 10⁶ cells/kg.

Ten patients (median age, 64 years; range, 41-71; 50% male) received OriCAR-017 as of the Apr. 30, 2022, data cutoff date, with results for 10 patients available for the safety and efficacy analyses. Participants received a median of six (range, 3-17) previous lines of therapy, including five patients (50%) treated with prior BCMA-directed CAR T-cell therapy.

Safety and tolerability of the OriCAR-017 regimen served as the trial’s primary endpoints. Secondary endpoints included measurements of treatment efficacy.

Median follow-up was 175.5 days (range, 35-281).

Key findings

The investors reported no dose-limiting toxicities during the study.

All patients experienced either grade 3 or grade 4 neutropenia, thrombocytopenia, leukopenia and lymphopenia. Grade 3 or grade 4 anemia occurred in 87.5% of patients.

Cytokine release syndrome occurred after CAR-T infusion in all 10 patients eligible for the safety analysis. No cases of grade 3 or higher CRS occurred during the study.

Likewise, no cases of treatment-related neurotoxicity occurred among patients who received OriCAR-107.

The efficacy results revealed that all patients eligible for the analysis had an objective response to therapy, including six patients with a complete or stringent complete response, three patients with a very good partial response and one patient with a partial response to therapy.

Additionally, all five patients who previously received BCMA-directed CAR-T had an objective response to OriCAR-107 — two stringent complete response, two very good partial responses and one partial response.

All 10 patients achieved minimal residual disease (MRD)-negative status as determined by bone marrow flow cytometry at a follow-up evaluation 28 days after CAR-T infusion. Five patients maintained a MRD-negative status as of a 6-month follow-up evaluation.

Clinical implications

Early results from this phase 1 trial show that OriCAR-107 has promising efficacy and a favorable safety profile, Huang said.

Notably, the treatment appears effective in patients who experienced disease progression after receiving BCMA-directed CAR T cells, he added.

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