OA – 12: Interim phase 2 study results of durcabtagene autoleucel (PHE885), a T-Charge™ manufactured BCMA-directed CAR-T cell therapy in patients (pts) with r/r multiple myeloma (RRMM)

Introduction: Durcabtagene autoleucel (PHE885) is a novel BCMA-directed CAR-T cell product manufactured using the T-Charge™ platform that preserves T-cell stemness and reduces manufacturing time to < 2 d, allowing for short door-to-door times. A phase 1 trial reported high response rates (ORR=98%) with no unexpected safety findings in heavily pretreated pts with aggressive RRMM. Here we report the interim analyses from the open-label, single-arm, multicenter phase 2 trial of PHE885 in pts with RRMM (NCT05172596).

Methods: Eligible pts had RRMM, were ≥18 y old, and had received ≥3 prior lines of therapy. The primary endpoint was ORR. Secondary outcomes included CRR, PFS, OS, and safety. Efficacy analysis set (EAS) consisted of pts infused with in-specification PHE885 at 10e6 cells and with ≥6 mo postinfusion follow-up (or discontinued early). The safety and full analysis set (FAS) included all infused pts regardless of disease measurability, dose, or follow-up.

Results: As of Jan 9, 2024, 161 pts were enrolled and 145 pts were infused: 34 pts at the 5e6 target dose and 111 pts at the 10e6 target dose. Robust cellular expansion was observed by qPCR. Among infused pts, median (range) age at enrollment was 61 y (35-78); 63% of pts were male. 27% of pts had ≥5 prior lines of therapy; 77% of pts were triple-class refractory. At study entry, 45% of pts had stage II disease (R-ISS), 18% had stage III. 16% of pts had high-risk cytogenetics. 33% of pts had ≥50% bone marrow plasma cells at baseline. 55% of pts required bridging chemotherapy prior to infusion; all pts received lymphodepletion. With median follow-up of 8.3 mo (6.0-13.4), ORR (≥PR) by IRC assessment in the EAS (N=62) was 92%, 95% CI [82.2-97.3%], meeting the primary endpoint (P< 0.001); CRR (CR+sCR) was 53% [40.1-66.0%]. 6-mo PFS probability was 82% [69.0-90.1%]. In the FAS for pts with ≥6 mo follow-up (N=107), ORR (≥PR) was 97% [92.0-99.4%]; CRR was 53% [43.4-63.0%]. 6-mo PFS probability was 86% [78.1- 91.7%]. In the safety set (N=145), all pts experienced at least 1 AE. The most common gr ≥3 AEs occurring in ≥20% of pts were neutropenia, anemia, and thrombocytopenia. Any-gr CRS was reported in 96% of pts; 6% had gr ≥3. Median time to CRS onset was 8 d (1-15), and median duration was 4 d. ICANS occurred in 13% of pts; 4% had gr ≥3. HLH, MAS, or IEC-HS was reported in 10% of pts; 6% had gr ≥3. In total 14 pts died of any cause; among them 4 pts died within 30 d of infusion. Cause of death was AE in 10 pts (9 pts at the 10e6 dose, among them 5 due to infections) and MM progression in 4 pts (3 at the 10e6 dose). First results of the primary efficacy analysis will be presented at the meeting.

Conclusions: T-Charge™-manufactured PHE885 produces high response rates with a manageable safety profile in RRMM. Efficacy thus far has appeared comparable between doses, with a trend toward better safety at the 5e6 dose. Longer follow-up is needed to fully assess durability and response rates as late conversions to CR/sCR have been observed.