653. Myeloma/Amyloidosis: Therapy, excluding Transplantation: Bispecific T Cell Engager Therapies and Novel Targeting Agents
Ajai Chari, Jesus G. Berdeja, Albert Oriol, et al.
Authors Conclusion from the Abstract: GPRC5D is a novel target for MM and in the first clinical report of this first-in-class agent, encouraging clinical activity with manageable safety was observed with talquetamab in heavily pretreated pts with RRMM. An MTD has not been defined and dose escalation continues, with the study nearing an RP2D. Encouraging clinical activity supports monotherapy development and combination approaches.
Deepu Madduri, Ashley Rosko, Jason Brayer, et al.
Authors Conclusion from the Abstract: In this updated analysis of the first-in-human study, REGN5458 continues to show an acceptable safety profile and durable efficacy in heavily pre-treated patients with RRMM. Enrollment in the Phase 1 dose escalation portion is ongoing, and the Phase 2 portion of the study is recruiting.
Adam D. Cohen, Simon J Harrison, Amrita Krishnan, et al.
Authors Conclusion from the Abstract: BFCR4350A monotherapy demonstrates promising activity in heavily pre-treated R/R MM, with deep and durable responses observed in pts with HR cytogenetics, triple-class refractory disease, and/or prior exposure to anti-CD38 mAbs, CAR-Ts, or ADCs. Toxicity was manageable, with C1 single step-up dosing effectively mitigating the risk for severe CRS and allowing escalation to clinically active doses. Updated data will be presented.
Cesar Rodriguez, Anita D'Souza, Nina Shah, et al.
Authors Conclusion from the Abstract: TNB-383B is well tolerated at doses up to 40 mg, without the need for step/split dosing. A preliminary ORR of 52% (12/23) was observed at doses ≥ 5.4 mg, including deep (6 PR / 3 VGPR / 3 CR) and durable (up to 24 weeks) responses despite dosing only every 3 weeks. Enrollment into the dose escalation arm is ongoing; updated data will be presented at the meeting.
Marc S. Raab, Nicola Giesen, Christof Scheid, et al.
Authors Conclusion from the Abstract: Targeting activating BRAF mutations in rrMM by combining the BRAF inhibitor, encorafenib, and the MEK inhibitor, binimetinib, induces rapid and deep responses in the majority of pts. No new safety signal has been observed when compared to prior reports on these compounds. The study reached its primary endpoint with fewer pts than expected. The primary efficacy and safety analysis will be presented at the conference.
Fredrik Schjesvold, Vincent Ribrag, Paula Rodriguez-Otero, et al.
Authors Conclusion from the Abstract: C, C+V and C+V+A demonstrated manageable safety and tolerability in heavily pretreated pts with RRMM. Preliminary efficacy results show moderate activity of the combinations in all-comers and higher activity in t(11;14) pts, supporting a biomarker-driven approach in the development of V in MM. Further biomarker analyses may provide insight into the pt subgroups that may benefit from combined MAPK and BCL-2 inhibition, and the contribution of PD-L1 inhibition.