Targeting B-cell maturation antigen (BCMA) with GSK2857916 antibody-drug conjugate provides durable responses in patients (PTS) with heavily-pretreated relapsed/refractory multiple myeloma (RRMM): Preliminary results from study BMA117159

Background: BCMA, a cell-surface receptor required for late-stage B-cell development and survival, is broadly expressed on MM cells. The humanized IgG1 antibody-drug conjugate GSK2857916 selectively binds BCMA and releases active cytotoxic monomethyl auristatin-F (MMAF) during cellular uptake. GSK2857916 is afucosylated to enhance antibody-dependent cell-mediated cytotoxicity. We report results from the Part 2 expansion of a study evaluating the safety, tolerability and clinical activity of GSK2857916 mo-notherapy. Methods: This was a single-arm, open-label, 2-part Phase I trial (BMA117159;NCT02064387). Eligible pts with RRMM had undergone stem cell transplantation (if eligible) and treatment with alkylators, proteasome inhibitors (PI) and immunomodulators (IMiD), and had a progression ≤60 days after last therapy. Primary study objectives were safety and determining the recommended Phase 2 dose (RP2D; established as 3.4 mg/kg in Part 1; Blood 2016;128:1148). In Part 2 GSK2857916 was dosed at RP2D via 1-h intravenous infusion q3w, until unacceptable toxicity, consent withdrawal or completion of 16 treatment cycles. Primary prophylaxis for infusion-related reactions (IRR) was not permitted. Pts received steroid eye drops to mitigate MMAF-associated corneal events. Results: In Part 2 35 pts with MM were treated (median age 60 years [range 46-75]; 49% male). Most pts (57%) had received ≥5 prior lines of therapy (range 1->10); 97% and 91% were refractory to PIs and IMiDs, respectively (all pts had received), 89% were double-refractory to PI/IMiDs, 37% were refractory to daratumumab (40% had received). Median number of GSK2857916 infusions: 5 (range 1-13); 54% pts received ≥5 infusions. Overall response rate (ORR) was 60% (21/35; 95%CI 42.1-76.1), including 1 stringent complete response (sCR), 2 CR, 15 very good partial response (VGPR) and 3 PR. In pts previously treated with daratumumab, ORR was 43% (6/14, 95%CI 17.7-71.1). Median duration of response was not reached; median progression-free survival (PFS) was 7.9 months (95%CI 3.1-not estimable). All pts had ≥1 adverse event (AE); the most frequent any-cause AEs (≥25%) were corneal events (63%), thrombo-cytopenia/platelet count decreased (57%), anemia (29%), aspartate amino-transferase increased (29%) and cough (26%). Corneal events (most frequent [≥20%]: vision blurred, dry eye, photophobia) were mostly Grade (Gr)1/2 and reversible. Gr3/4 AEs reported in ≥10% of pts: thrombocytopenia/platelet count decreased (34%) and anemia (14%). Serious AEs were reported in 40% (14/35) of pts. Eight pts had IRRs (2 Gr1, 3 Gr2, 3 Gr3) with the first infu-sion, which resolved and did not recur with subsequent infusions. Treatment was discontinued by 18 pts owing to: disease progression (n=15), AE (n=2; thrombocytopenia, creatinine phosphokinase elevation), patient decision (n=1). Treatment for 17 pts is ongoing. Conclusions: Single-agent GSK2857916 demonstrated a manageable safety profile and strong clinical activity with deep (51% ≥VGPR) and durable (median PFS 7.9 months) responses in pts with heavily pre-treated RRMM. The mechanism of action of GSK2857916 is distinct from currently approved MM drugs; further mono-therapy and combination studies are planned. Study funded by GSK; drug linker technology licensed from Seattle Genetics; monoclonal antibody produced using POTELLIGENT® Technology licensed from BioWa. Editorial support from Fishawack Indicia, funded by GSK. This abstract was originally presented at ASH 2017.