Pfizer Announces Phase I Data of BCMA-CD3 Bispecific Antibody PF-06863135 in Relapsed/Refractory Multiple Myeloma at ASH 2020

On December 7, Pfizer announced the safety and efficacy data from its Phase I clinical study (NCT03269136) of PF-06863135, a BCMA-CD3 bispecific antibody targeting B-cell maturation antigen (BCMA), for the treatment of relapsed/refractory multiple myeloma (MM). Data from 30 patients with relapsed/refractory MM showed that subcutaneous administration of PF-06863135 was well-tolerated across all dose levels, with no dose-limiting toxicities observed. Clinical responses were achieved in 83% of patients at the highest dose level.

PF-06863135 is a bispecific antibody. BCMA protein is highly expressed in cancer cells of patients with multiple myeloma (MM). PF-06863135 presents the BCMA protein on tumor cells to the CD3 protein specifically expressed by T cells, thereby activating the immune system to recognize and kill tumor cells. The subcutaneous administration design aims to deliver higher doses of PF-06863135 to patients while significantly reducing adverse reactions compared to intravenous administration.

The primary objective of this study was to evaluate the safety and tolerability of subcutaneous administration of PF-06863135, in order to determine the maximum tolerated dose (MTD) for patients and thereby identify the optimal dosing regimen for Phase II clinical trials. During the dose escalation phase, no dose-limiting toxicities were observed at any evaluated dose level (ranging from 80 to 1000 μg/kg weekly). Cytokine release syndrome (CRS) was reported in 73.3% of patients, with all cases being Grade 1 (56.7%) or Grade 2 (16.7%). Grade 3 or higher adverse events (AEs) occurred in more than 10% of patients, including lymphopenia (53.3%), neutropenia (26.7%), thrombocytopenia (16.7%), and anemia (16.7%).

The overall response rate (ORR) was 80% in 20 patients receiving effective doses ranging from 215 to 1,000 μg/kg per week. Among these, 6 patients achieved stringent complete response or complete response, 3 patients achieved very good partial response, and another 6 patients achieved partial response. Three of the responding patients had previously received at least one prior BCMA-targeted therapy. The ORR in the highest dose cohort (1,000 μg/kg) was 83% (5/6). Based on these data, the recommended Phase II clinical trial dose was established as 1,000 μg/kg per week.

Multiple myeloma is a blood cancer that affects the bone marrow’s production of plasma cells, which are blood cells that help the body fight infection. The latest available data indicate that there are 32,270 new cases of multiple myeloma annually in the United States and approximately 160,000 cases worldwide. Despite continuous improvements in treatment options, the disease remains incurable. The median overall survival is approximately 5 years, with most patients receiving four or more lines of therapy.