Part 1 Results of a Dose-Finding Study of Belantamab Mafodotin in Combination with Pomalidomide and Dexamethasone for the Treatment of Relapsed/Refractory Multiple Myeloma (RRMM)

Background: Belantamab mafodotin (belamaf) is a first-in-class antibody-drug conjugate (ADC) targeting B-cell maturation antigen (BCMA) that has shown clinically meaningful activity as a single agent in relapse/refractory multiple myeloma (RRMM). Pre-clinical studies demonstrate that the immune mediated anti-myeloma activities of belamaf are enhanced by immunomodulatory drugs (IMiDs) providing the rationale for combining Belamaf with pomalidomide (POM). The Algonquin study is an ongoing Phase 1/2 trial designed to evaluate the recommended Part 2 dose (RP2D), safety, and preliminary efficacy of belamaf in combination with POM and dexamethasone (DEX) (B-Pd) in patients (pts) with RRMM. The initial data from the dose-escalation phase of the study identified 2.5 mg/kg in combination with standard dosing of POM/DEX as the maximum tolerated dose (MTD) (Trudel et al. ASH 2020). Here we report updated safety and efficacy data and additional dosing cohorts used to identify the RP2D. Methods: Eligibility required > 1 prior lines of treatment (LoT), lenalidomide (LEN) and proteasome inhibitor (PI) exposure and refractoriness to the last LoT. POM was administered at 4 mg days 21/28 days, DEX 40 mg (20 mg age > 75 years) weekly in conjunction with IV belamaf SINGLE (1.92 or 2.5 mg/kg) Q4W, 2.5 mg/kg LOADING dose followed by 1.92 mg/kg Q4W from cycle 2+, 2.5 mg/kg dosed Q8W (BIMONTHLY) or Q12W (TRIMONTHLY), or belamaf SPLIT (2.5 or 3.4 mg/kg), split equally on days 1 and 8 Q4W. Dose escalation was accomplished using a standard 3+3 dose escalation design. Responses were assessed by International Myeloma Working Group (IMWG) criteria and adverse events (AEs) were graded by CTCAE criteria except for corneal findings which were also graded by the pre-specified keratopathy and visual acuity (KVA) scale. Up to 12 pts could be enrolled at dose levels not exceeding the MTD to inform the R2PD. Results: At cut-off (July 15, 2021), 60 pts had been enrolled in the following dose levels and schedules: 1.92 SINGLE (n=12), 2.5 SINGLE (n=7), 2.5 LOADING (n=5), 2.5 BIMONTHLY (n=12), 2.5 TRIMONTHLY (n=11), 2.5 SPLIT (n=8) and 3.4 SPLIT (n=5). The median age was 65 years (range 36-81) and median prior LoT was 3 (1-5). Prior therapies (exposed/refractory) included stem cell transplant (57%), PI (100%/82%), LEN (100%/90%) and daratumumab (DARA) (58%/100%). 76% were refractory to LEN and a PI and 48% to LEN, a PI and DARA. The most frequent AEs regardless of attribution were keratopathy (an