Results: As of June 5, 2023, 35 patients were enrolled with a median follow-up of 11.4 months (range, 1.2–14.9) in the QW cohort (N=16) and 7.7 months (range, 1.6–10.8) in the Q2W cohort (N=19). Median ages were 69.5 years (range, 49–78) and 63.0 years (range, 43–76), respectively; 41.7% and 33.3% of pts had high-risk cytogenetics (del[17p], t[4;14], or t[14;16]) and 12.5% and 10.5% of pts had extramedullary disease, respectively. Median prior LOT were 3 in both cohorts; 25.0% and 21.1% were triple-class refractory, respectively, and 6.3% were penta-drug refractory (all in QW cohort). Prior treatments included CAR-T (18.8% and 0%), BsAb (6.3% and 0% [0% refractory]), and anti-CD38 Ab (75.0% and 73.7% [56.3% and 36.8% refractory]) in the QW and Q2W cohorts, respectively; 31.3% and 15.8% had prior pom exposure (18.8% and 5.3% refractory). All pts had ≥1 AE; most common were dysgeusia (77.1%), CRS (74.3%; most grade 1/2, 2.9% grade ≥3), and neutropenia (60.0%). Grade 3/4 AEs occurred in 88.6% of pts; most common were neutropenia (48.6%), anemia (25.7%), and thrombocytopenia (20.0%). Nail, skin, and rash toxicities occurred in 65.7%, 40.0%, and 20.0% of pts (majority grade 1/2 with no discontinuations), respectively. ICANS occurred in 2 pts (both grade 1). Infections occurred in 71.4% of pts (22.9% grade 3/4); most common were pneumonia (20.0%) and COVID-19 (14.3%). AEs led to dose reduction or schedule change of tal in 34.3% of pts and dose reduction of pom in 31.4% of pts. Two pts (5.7%) in the Q2W cohort had AEs, myocardial infarction and pulmonary embolism (PE), that led to treatment discontinuation (not drug related). One death due to PE occurred (same pt who discontinued treatment). ORR was 86.7% and 83.3% in the QW and Q2W cohorts, respectively, with ≥CR in 60.0% and 44.4% and ≥VGPR in 86.7% and 77.8%, respectively. ORRs were consistent across pt subgroups (>80% independent of prior pom or CAR-T exposure). Median time to first response was 1.0 month (range, 0.9–2.1) in the QW cohort and 1.3 months (range, 0–4.8) in the Q2W cohort. At 6 months, 100% of responders were still responding in both cohorts. Median DOR and PFS were not reached, with 6-month PFS rates of 93.3% (QW) and 88.9% (Q2W).

Conclusions: In this first reported combination of a GPRC5D-targeted therapy and an IMiD, tal + pom showed rapid, deep responses in pts with RRMM and ≥2 prior LOT. The safety profile of the combination, including grade 3/4 hematologic toxicity, was consistent with the individual agents, with no evidence of additive hematologic toxicities; additionally, there were low rates of treatment discontinuation due to AEs. The promising efficacy and manageable safety profile of this combination further supports tal as a versatile combination partner and warrants further evaluation of this regimen.