Bristol Myers announces results of golcadomide studies in Non-Hodgkin Lymphoma

Bristol Myers announced the results of two early studies evaluating combinations of potential first-in-class CELMoD agent golcadomide in non-Hodgkin lymphomas. These data are being presented in separate posters at the 2023 American Society of Hematology Annual Meeting from December 9-12. In the dose expansion phase of this Phase 1b study, patients were randomized 1:1 to golcadomide at one of two recommended Phase 2 dose levels plus R-CHOP-21 for a fixed duration of 6 cycles. A total of 65 (83.3%) patients completed 6 cycles of the combination with 13 discontinuing treatment. There were 71 patients evaluable for efficacy, and results showed: Overall response rate (ORR) at end of treatment rate was 84.5% in patients overall, with 87.9% of patients in the DL1 arm achieving a complete metabolic response (CMR) compared to 63.6% in the DL-1 arm. Minimal residual disease negativity at the end of treatment was achieved in 93% (14/15) of patients treated with 0.4 mg of golcadomide plus R-CHOP compared to 70% (7/10) treated with 0.2 mg of golcadomide plus R-CHOP. At both DL1 and DL-1, steady-state levels of golcadomide reduced Ikaros over 80%, to levels predicted to optimize tumor cell killing and to stimulate T and NK cells. In the safety population (n=78), the majority of patients (98.7%) experienced at least one treatment-emergent adverse event (TEAE). Grade 3/4 TEAEs were primarily hematologic with neutropenia (89.7%), thrombocytopenia (42.3%) and anemia (32.1%) being the most common. Any grade febrile neutropenia was reported in 21.8% of patients. Median relative dose intensity of key R-CHOP components was maintained at greater than90%. A separate poster detailed the efficacy and safety results from the dose expansion segment of a Phase 1/2 open-label study of two doses of golcadomide plus rituximab in relapsed/refractory patients with non-Hodgkin lymphoma. Patients were heavily pre-treated with a median number of 4 prior therapies (range 1-11), including 61% who had prior CAR T. In patients evaluable for efficacy (n=26), the ORR was 42% (11/26) with 19% (5/26) achieving a complete response (CR). The median duration of response was 7.5 months (1.8-14.5). The ORR and CR rate was greater for patients in the 0.4 mg arm compared to the 0.2 arm (55% vs. 33% and 27% vs. 13%, respectively). In the study, neutropenia was the most common TEAE of any grade, occurring in 50% of patients (22/44). Febrile neutropenia was observed in 2 patients, with 1 patient at each dose level. A total of 6 patients had serious adverse events with only pneumonia and pyrexia occurring in more than 1 patient (2 each). There were 4 deaths on treatment during the study with one considered related to the study treatment.