Final Results of Phase 1 Clinical Trial of Belantamab Mafodotin Combined with Carfilzomib, Lenalidomide, and Dexamethasone for Multiple Myeloma after One to Three Prior Lines of Therapy
Results: With a data cutoff of June 10, 2024, 26 pts consented to phase 1, and 19 were enrolled; 6 pts at 1.4 mg/kg and 13 at 1.9 mg/kg (6 DLT evaluable pts in 1.4 mg/kg cohort and 12 DLT evaluable pts in the 1.9 mg/kg cohort). Median age was 63. Most pts were males 63%, 42% were black, and 53% had high-risk cytogenetics, including 1q gain and 1p deletion. 50% of pts with available ISS staging data at diagnosis had stage III, 42% were refractory to lenalidomide, 11% were bortezomib refractory, 26% were double refractory, and 26% were daratumumab refractory. The median lines of prior therapy was 1 (range 1- 3).
At the 1.4 mg/kg dose level, one DLT of grade 4 thrombocytopenia was reported out of 6 pts. No DLTs were reported among the 12 DLT evaluable pts enrolled at the 1.9 mg/kg dose level (6 pts as part of the dose escalation portion and 6 pts for dose expansion).
The most common adverse events were non-specified eye disorders (total; ≥G3) (94.7%; 31.6%), blurred vision (89.5%; 36.8%), fatigue (57.9%; 0%), hypokalemia (52.6%; 10.5%), cough (47.4%; 0%), diarrhea (47.4%; 0%), and pain (47.4%; 0%).
15 pts experienced G2(+) corneal events per KVA (26 total G2(+) events), and 15 pts experienced a decline of 2 or more lines on the Snellen Visual Acuity scale (25 events). After a median follow-up (IQR) of 16.1 months (11.4; 24.1), 3 pts progressed. The total and median number of cycles of belantamab were 73 and 5 cycles, respectively. All pts achieved a best response of at least a PR, the VGPR(+) rate was 73.7%, and the CR(+) rate was 52.6%, including 52.6% and 36.8% with MRD negativity 10^-5 and 10^-6 by flow cytometry, respectively. Out of 7 pts with R-ISS-III, 57.1% achieved VGPR(+). Out of 8 pts with IMWG high risk cytogenetics, 5 pts (62.5%) achieved a VGPR or better. Responses are expected to deepen with further follow-up. In total, 9 pts achieved sCR, which exceeds the protocol-directed criterion to proceed to Phase 2 at the RPD2 dose. 13 pts are off treatment due to consent withdrawal (n=4), investigator decision post 18 cycles (n=4), participant non-compliance (n=1), and toxicity (n=1).
Conclusions: This phase 1 trial established the MTD of belantamab of 1.9 mg/kg every 8 weeks in combination with KRd. KRd-B is effective even in pts with high-risk MM. Despite the dosing schedule of every 8 week Belamaf dosing, clinically significant keratopathy was common. Pts with high-risk newly diagnosed MM will be enrolled in the phase 2 portion of this trial.