Trial in progress: QUINTESSENTIAL—a phase 2 study of arlocabtagene autoleucel (arlo-cel) in patients with relapsed/refractory multiple myeloma (RRMM)

Abstract Background and Significance Limited treatment options exist for patients (pts) with RRMM who have been exposed to 3 or more drug classes, including immunomodulatory drugs (IMiD), anti-CD38 antibodies, proteasome inhibitors (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 quadruple-class exposed (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 heavily pretreated RRMM, including pts who received prior BCMA-targeted therapy. Following a single infusion of arlo-cel (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). These outcomes from the phase 1 study support further development of arlo-cel in clinical trials. Study Design and Methods QUINTESSENTIAL (NCT06297226) is an open-label, multicenter, phase 2 study evaluating arlo-cel in pts with RRMM. For analyses, enrollment is planned at 175 pts. Key inclusion criteria were 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. 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 patient receives arlo-cel, with a subsequent long-term follow-up study continuing for ≤15 years. This is a trial in progress and will recruit at ~47 centers across the USA, Canada, and Japan. The first patient first visit was achieved on March 21, 2024.

Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.