BCMA-CD3 dual-specific antibodies! Pfizer PF-0686315 Once a week subsethic injection to treat multiple myeloma: 83% total remission rate!

December 09, 2020 // -- Pfizer (Pfizer) recently announced the safety and clinical response results of the PF-06863135 Phase I Study (NCT03269136) at the 62nd Annual Meeting of the American Society of Hematology (ASH).
PF-06863135 is a two-specific antibody in study that targets BCMA and CD3.
data from 30 R/R MM patients showed that PF-06863135 was safe at all supully injectable dose levels and no dose-limiting toxicity was observed.
at the highest dose level, 83% of patients achieved a clinical response.
PF-06863135 is a BCMAxCD3 dual-specific antibody designed to bind to highly expressed B-cell mature antigens (BCMA) and cancer-fighting T-cell surface CD3 bodies on the surface of multiple myeloma cells to activate the immune response.
the binding affinity of PF-06863135 to BCMA and CD3 was optimized to make T-cell-mediated anti-myeloma more active.
PF-06863135 is intended to allow higher doses than intravenous injections without increasing adverse events.
This Phase I study (NCT03269136) is an open label, multi-dose, multi-center, dose increment, safety, pharmacodynamics (PK) and pharmacodynamics study in adult MM patients who have relapsed after receiving standard therapy or who are difficult to treat with standard therapy.
the study consists of two parts, part 1 evaluates the safety and tolerance of PF-06863135 incremental dose levels.
the study included 80 patients and assessed PF-06863135 injected intravenously or under the skin.
results of intravenous drug use were reported at the ASH Annual Meeting in 2019.
the main objective of this part of the study, published at this year's ASH Annual Meeting, was to assess the safety and toerability of PF-06863135 injections, to determine the maximum to-dosage, and to select the recommended phase 2 dose.
, no dose-limiting toxicity of subsult dose levels (80-1000 μg/kg per week) was observed during dose increment.
73.3% of patients developed cytokine release syndrome (CRS), limited to level 1 (56.7%) or level 2 (16.7%).
> ≥-level adverse events that occur in ≥10% of patients include lymphocytic cell reduction (53.3%), neutral granulocyte reduction (26.7%), thyrocyte reduction (16.7%) and anemia (16.7%).
effective biotherapy target on the surface of multiple myeloma cells (pictured from literature: PMID: 30545798) had a total remission rate (ORR) of 80% in 20 patients treated at an effective dose range of 215-1000 μg/kg once a week.
of these 20 patients, 6 received strict total remission (sCR) or full remission (CR), 3 received very good partial remission (VGPR), and 6 received partial remission (PR).
3 patients with therapeutic responses had received at least one BCMA targeted therapy.
the orR is 83% (n-5/6) at a maximum dose of 1000 μg/kg.
based on these data, the recommended phase 2 dose is 1000 μg/kg once a week.
"Despite advances in treatment, multiple myeloma (MM) remains incurable and a major breakthrough in treatment is urgently needed for patients," said Jeff Settleman, senior vice president and chief scientific officer of Pfizer's oncology research and development division.
very high remission rates observed in PF-06863135 treatment, coupled with manageable safety and ease of administration underscore the potential impact the drug may have on the population of patients with this devastating disease.
these findings support the continued development of PF-06863135 in the treatment of multiple myeloma, neither as a single therapy nor in combination with standard or new therapies.
() Original source: PFIZER REPORTS POSITIVE CLINICAL DATA FOR BCMA-CD3 BISPECIFIC ANTIBODY (PF-06863135) IN MULTIPLE MYELOMA