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    Cellular and T cell engager Immunotherapy

    Category: Cellular and T cell engager Immunotherapy

    Trial in Progress: QUINTESSENTIAL—A Phase 2 Study of Arlocabtagene Autoleucel (arlo-cel) in Triple- and Quad-Class Exposed Patients With Relapsed and Refractory Multiple Myeloma (RRMM)

    (PA-077) Trial in Progress: QUINTESSENTIAL—A Phase 2 Study of Arlocabtagene Autoleucel (arlo-cel) in Triple- and Quad-Class Exposed Patients With Relapsed and Refractory Multiple Myeloma (RRMM)

    Friday, September 19, 2025

    Introduction:      Limited treatment options exist for patients (pts) with RRMM who are triple-class exposed (TCEx: immunomodulatory drugs [IMiD], anti-CD38 antibodies, and proteasome inhibitors [PI]) and quad-class exposed (QCEx: IMiD, anti-CD38 antibodies, PI, and B-cell maturation antigen [BCMA]-targeted therapy). To address this unmet need, new treatment options are needed for late-line populations, which will continue to grow with more QCEx pts due to the approval of BCMA-targeted therapies in earlier lines. G protein-coupled receptor class C group 5 member D (GPRC5D) is an orphan receptor expressed on plasma cells, with limited expression elsewhere, making it a promising therapeutic target for MM. Data from a phase 1 first-in-human study (NCT04674813) suggested that arlo-cel, a GPRC5D-directed autologous chimeric antigen receptor (CAR) T-cell therapy, is safe and efficacious in pts with TCEx RRMM, including pts who received prior BCMA-targeted therapy. At the recommended phase 2 dose (RP2D) of 150×106 CAR T-cells, overall response rate (ORR) was 91% (21/23), median progression-free survival (PFS) was 18.3 months, and median overall survival (OS) was not reached in those with ≥3 prior lines of therapy (pLOT) (Bal S et al. ASH 2024. Abstract 922). Here, we present the study design of QUINTESSENTIAL (NCT06297226), an open-label, multicenter, phase 2 study evaluating arlo-cel in pts with TCEx and QCEx RRMM.

    Methods:   For analyses, enrollment is planned at 175 pts. Key inclusion criteria include age ≥18 years, confirmed diagnosis of MM as per International Myeloma Working Group (IMWG) criteria, ≥3 classes of MM treatment (including IMiD, PI, and anti‑CD38), and ≥3 pLOT. Pts must also have documented disease progression (PD) during or after the most recent regimen as per IMWG, measurable disease, and an ECOG performance status of 0 or 1. Pts who previously received a GPRC5D-targeted therapy are excluded. After screening, pts will undergo leukapheresis followed by bridging therapy. Pts will then receive lymphodepleting chemotherapy followed by a single infusion of arlo-cel at the RP2D of 150×106 CAR T-cells (range: 120–180×106). The primary endpoint is ORR by IMWG response criteria per an independent review committee in pts who are QCEx and received ≥4 pLOT. Key secondary endpoints are ORR and complete response rate in all pts. Other secondary and exploratory endpoints include time to response, duration of response, PFS, OS, minimal residual disease-negative status, and safety. Pts will be followed for ≤5 years after the last pt receives arlo-cel, with a subsequent long-term follow-up study continuing for ≤15 years.

    Results:   This is a trial in progress and will recruit at ~47 centers across the USA, Canada, and Japan. The first pt first visit was achieved on March 21, 2024.

    Conclusions:   This phase 2 study will evaluate the efficacy and safety of arlo-cel in heavily pretreated pts with RRMM.