A Study of Venetoclax in Combination With Pomalidomide and Dexamethasone in Participants With Relapsed or Refractory Multiple Myeloma

A Phase 2, Open-Label, Multicenter, Dose-Escalation and Expansion Study of Venetoclax in Combination With Pomalidomide and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma

This was an open-label, multicenter study designed to evaluate the safety and preliminary efficacy of venetoclax combined with pomalidomide and dexamethasone in participants with relapsed or refractory (R/R) multiple myeloma (MM) who received at least 1 prior line of therapy with documented evidence of progression during or after the participant's last treatment regimen. The study was designed to consist of 2 parts: Part 1 (dose escalation) and Part 2 (dose expansion). For Part 2 the participants were to be divided into 2 cohorts, participants positive for t(11;14) translocation and participants negative for t(11;14) translocation.

Following communication of the results of the primary progression-free survival (PFS) analysis from the Phase 3 BELLINI study (Study M14-031; NCT02755597), the company-sponsored MM studies were placed on partial clinical hold (PCH) in March 2019 by the United States (US) Food and Drug Administration and enrollment was halted. The sponsor did not pursue release of the PCH for this study; therefore, enrollment was not re-opened. In accordance with the terms of the PCH, participants who were deriving clinical benefit were allowed to continue to receive treatment. One participant was still active in Part 1 of the study when the sponsor decided not to pursue release of the PCH (in January 2020) and, therefore, continued to receive treatment and have regular assessments until disease progression. The study was discontinued when the last participant completed study treatment. No participants were enrolled in Part 2 of the study.

Inclusion Criteria:

• Relapsed or refractory (R/R) multiple myeloma (MM) with documented evidence of progression during or after the participant's last treatment regimen
• Measurable disease as described in the protocol
• Received at least 1 prior line of therapy as described in the protocol
• Must meet prior antimyeloma treatment parameters, as described in the protocol, and includes:
• Received at least 2 consecutive cycles of lenalidomide or a lenalidomide-containing regimen
• Refractory to lenalidomide
• Exposed to a proteasome inhibitor (PI) alone or in combination with another agent
• Had a response of partial response (PR) or better to prior therapy based on the investigator's determination of response as defined by International Myeloma Working Group (IMWG) criteria
• Has t(11;14) status as described in the protocol and meets the following criteria:
• For Part 1: MM participants independent of cytogenetic profile
• For Part 2, Arm A: participant must be t(11;14) positive
• For Part 2, Arm B: participant must be t(11;14) negative
• An Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Adequate kidney, liver and hematologic laboratory values

Exclusion Criteria:

• Previous treatment with venetoclax or other BCL-2 inhibitors, or previous treatment with pomalidomide
• Known sensitivity to any IMiDs
• Allogenic or syngeneic stem cell transplant within 6 months before the first dose of study drug or active ongoing graft versus host disease
• Autologous stem cell transplant within 12 weeks before the first dose of study drug
• Known meningeal involvement of MM