Pfizer Reports 83% Overall Response Rate with Weekly Subcutaneous BCMA-CD3 Bispecific Antibody PF-06863135 in Relapsed/Refractory Multiple Myeloma

December 09, 2020 News /Bio ValleyBIOON/ --Pfizer(Pfizer) recently presented the safety and clinical response results from the Phase I study (NCT03269136) of PF-06863135 for the treatment of relapsed or refractory multiple myeloma (R/R MM) at the 62nd Annual Meeting of the American Society of Hematology (ASH). PF-06863135 is an investigational bispecific antibody targeting BCMA and CD3. Data from 30 patients with R/R MM showed that PF-06863135 had a manageable safety profile across all subcutaneous dose levels, with no dose-limiting toxicities observed. InAt the highest dose level, 83% of patients achieved a clinical response.

PF-06863135 is a BCMAxCD3 bispecific antibody designed to bind B-cell maturation antigen (BCMA), which is highly expressed on the surface of multiple myeloma cells, and the CD3 receptor on the surface of anti-tumor T cells, thereby bridging them to activate an immune response. The binding affinities of PF-06863135 for BCMA and CD3 have been optimized to enhance T cell-mediated anti-myeloma activity. Subcutaneous administration of PF-06863135 is intended to allow for higher doses than intravenous administration without increasing adverse events.

This Phase I study (NCT03269136) was an open-label, multiple-dose, multicenter, dose-escalation study evaluating the safety, pharmacokinetics (PK), and pharmacodynamics of PF-06863135 in adult patients with multiple myeloma (MM) who had relapsed after or were refractory to standard therapy. The study consisted of two parts; Part 1 assessed the safety and tolerability of escalating dose levels of PF-06863135. A total of 80 patients were enrolled and evaluated for intravenous or subcutaneous administration of PF-06863135. Preliminary results for intravenous administration were presented at the 2019 American Society of Hematology (ASH) Annual Meeting.

The primary objectives of this study presented at this year’s ASH Annual Meeting were to evaluate the safety and tolerability of subcutaneous PF-06863135, determine the maximum tolerated dose, and select the recommended Phase 2 dose. During the dose-escalation phase, no dose-limiting toxicities were observed at any subcutaneous dose level (80–1000 μg/kg weekly). Cytokine release syndrome (CRS) occurred in 73.3% of patients, limited to Grade 1 (56.7%) or Grade 2 (16.7%). Grade ≥3 adverse events occurring in >10% of patients included lymphopenia (53.3%), neutropenia (26.7%), thrombocytopenia (16.7%), andAnemia（16.7%）。

Effective Biotherapeutic Targets on the Surface of Multiple Myeloma Cells (Image source: PMID:30545798)

Within the effective dose range ofAmong the 20 patients treated with 215–1000 μg/kg once weekly, the overall response rate (ORR) was 80%.Among these 20 patients, 6 achieved stringent complete response (sCR) or complete response (CR), 3 achieved very good partial response (VGPR), and 6 achieved partial response (PR). Three of the responding patients had previously received at least one BCMA-targeted therapy.At a maximum dose of 1000 μg/kg, the ORR was 83% (n=5/6).Based on these data, the recommended Phase 2 dose is 1000 μg/kg once weekly.

PfizerTumorJeff Settleman, Senior Vice President of Research and Development and Chief Scientific Officer, stated, “Despite advances in treatment, multiple myeloma (MM) remains incurable, and there is an urgent need for significant therapeutic breakthroughs for patients. The very high response rates observed with PF-06863135, combined with its manageable safety profile and the convenience of subcutaneous administration, underscore the potential impact this drug may have on the patient population suffering from this devastating disease. These findings support the continued development of PF-06863135 in the treatment of multiple myeloma, both as a monotherapy and in combination with standard or novel therapies.”(Bioon.com)

Original Source: PFIZER REPORTS POSITIVE CLINICAL DATA FOR BCMA-CD3 BISPECIFIC ANTIBODY (PF-06863135) IN MULTIPLE MYELOMA