DP112 | UPDATED INTERIM RESULTS OF SONROTOCLAX + DEXAMETHASONE IN PATIENTS WITH T(11;14)-POSITIVE RELAPSED/REFRACTORY MULTIPLE MYELOMA: AN ALL-ORAL TREATMENT

BACKGROUND: Sonrotoclax (sonro; BGB-11417), a next-generation BCL2 inhibitor, is a more selective and pharmacologically potent inhibitor of BCL2 than venetoclax. BGB-11417-105 (NCT04973605) is an ongoing phase 1b/2 study of sonro as mono- or combination therapy in patients (pts) with t(11;14)-positive R/R MM. Updated sonro + dexamethasone (dex) data are presented. METHODS: Eligible pts had R/R MM with centrally confirmed t(11;14) and received oral sonro (320 or 640 mg QD) + dex (40 mg QW). Tx-emergent adverse events (TEAEs) were graded by CTCAE v5.0 and efficacy was assessed by the investigator per IMWG criteria. RESULTS: As of 20 Jan 2025, 14 and 36 evaluable pts were enrolled in the sonro 320mg and 640mg cohorts, respectively; median (range) follow-up was 6.2 m (2.6-34.5) and 12.1 m (0.1-28.9), respectively. Pts in both cohorts had a median of 3 prior lines of tx; 78.6% (320mg) and 66.7% (640 mg) of pts were refractory to 3 tx classes. At data cutoff, 50.0% (320 mg) and 38.9% (640mg) remained on tx; progression was the most common reason for discontinuation (35.7% and 41.7%, respectively). ORRs were 64.3% (320mg) and 80.6% (640 mg), with very good partial response or better rates of 35.7% and 55.6%, respectively (Figure). Median time to response was 0.7 m in both cohorts. Median duration of response was 5.9 m for 320 mg and 12.2 m for 640 mg. Median (95% CI) PFS was 6.6 m (2.9-NE) for 320mg and 13.3 m (9.0-19.6) for 640 mg. The most common TEAEs were fatigue (35.7%) in the 320-mg cohort, and insomnia (38.9%) and diarrhea (38.9%, all grade 1/2) in the 640 mg cohort. Grade ≥3 TEAEs occurred in 5 pts (35.7%) in the 320 mg cohort and 17 pts (47.2%) in the 640-mg cohort; serious TEAEs occurred in 3 (21.4%) and 10 (27.8%), respectively. Grade ≥3 hematologic TEAEs occurred in 1 (7.1%) and 9 (25.0%) and grade ≥3 infections in 3 (21.4%) and 4 (11.1%) pts, respectively. Two pts in each cohort died during the tx-emergent part for reasons unrelated to tx (320 mg, pneumonia, RSV, and COVID-19; 640 mg, hypoventilation [related to pulmonary involvement with PD] and metastatic pancreatic cancer). Four more deaths occurred >30 d after the last 640-mg dose. CONCLUSIONS: This ongoing study showed that the all-oral combination of sonro + dex is tolerable, with low rates of infection and hematologic toxicity, and promising efficacy, with an ORR of 81% in the 640 mg cohort, in this t(11;14)-positive R/R MM population. Additional tx combinations with sonro are being investigated.