PX-171-003-A1, an Open-Label, Single-Arm, Phase (ph) II Study of Carfilzomib (CFZ) in Patients (pts) with Relapsed and Refractory Multiple Myeloma (R/R MM): Long-term Follow-Up and Subgroup Analysis.

8027 Background: CFZ is a novel, highly selective epoxyketone proteasome inhibitor in development for treatment (tx) of MM. Single-agent CFZ has shown durable activity in up to 63% of pts with relapsed MM. PX-171-003-A1 was an open-label, single-arm ph 2b trial in pts with advanced refractory MM. Methods: Pts received and were refractory to ≥2 prior therapies (bortezomib [BTZ], either thalidomide or lenalidomide, and an alkylator). CFZ was given on d1, 2, 8, 9, 15, 16 of 28-day cycles (C), (20 mg/m2 in C1; 27 mg/m2 in C2–12). Primary endpoint was overall response rate (ORR). Secondary endpoints were clinical benefit response (CBR), duration of response (DOR), overall survival (OS), and safety. Cytogenetic data (if available), peripheral neuropathy (PN) history, International Staging System (ISS)/Durie-Salmon staging, and prior tx history were collected for subset analyses. Responses assessed per International Myeloma Working Group criteria were confirmed by Independent Review Committee. Results: Of 266 pts enrolled, 257 were response-evaluable. ORR was 24% with median DOR of 7.4 mo (95% CI 6.2–10.3). 71 of 229 pts had ≥1 cytogenetic abnormality and achieved an ORR of 28%, with median DOR of 7 mo (95% CI 4–10). Median OS was 15.5 mo (95% CI 12.7–19.0). The most common treatment-emergent adverse events (AEs) ≥ G3 were primarily hematologic. New-onset PN and PN ≥G3 were infrequent. 27 pts completed 12C and continued on extension protocol PX-171-010. Notably, there was no difference in DOR and TTP for pts achieving MR vs ≥PR, suggesting that distinguishing these subsets may not translate into clinically meaningful differences in the context of CFZ treatment. Conclusions: Single-agent CFZ achieved significant, durable responses in 36% of pts with BTZ and IMiD refractory MM, including those with unfavorable cytogenetics. CFZ was well-tolerated and AEs were clinically manageable with no new, unexpected, or cumulative toxicities. Baseline characteristic Total n ≥PR, % ≥MR, % Overall 257 24 36 Prior therapies <5 110 25 33 ≥5 147 24 36 Cytogenetic status Normal/favorable 158 24 37 Unfavorable 71 28 32 ISS stage I 76 32 46 II 96 25 35 III 78 18 24