The median patient age was 61, with 13 patients considered high-risk, including those with high-risk cytogenetics. The majority of patients received six or more prior lines of therapy and all patients had received at least one proteasome inhibitor and at least one IMiD. Ninety-one percent of the patients had received daratumumab and eighty-six percent of the patients had received an autologous stem cell transplant. Peak T-cell expansion was observed between days 14 and 21, which is more gradual than the five to 14-day peak expansion typically seen with other CAR-T therapies and was associated with less acute cytokine release and other adverse effects. Poseida has not conducted a head-to-head study comparing P-BCMA-101 to other CAR-T therapies.
Interim Safety Update
All 23 patients treated to as of the data cutoff date received a single dose of P-BCMA-101 following a standard conditioning regimen of lymphodepleting chemotherapy consisting of 300 mg/m2 cyclophosphamide and 30 mg/m2 fludarabine. Two cases of suspected CRS (9.5%) were observed, one Grade 1 and one Grade 2. In both cases, the suspected CRS was minimal and transient and neither patient was treated with an IL-6 inhibitor or steroids, which are standard therapies for CRS. In addition, no patient has required admittance to the intensive care unit for CRS or neurotoxicity. In both patients, peak measured IL-6 levels, a suspected correlate marker for CRS, were under 50 pg/ml, well below the levels typically associated with meaningful or serious CRS. One case of suspected neurotoxicity (4.8%) was observed in a patient with mental status changes prior to treatment and was treated with an IL-6 inhibitor and steroids. No dose limiting toxicities have been reported. To date, use of the safety switch has not been indicated in any patient.
“We recently received RMAT designation from the FDA and believe the data support our plan to pursue a registrational clinical trial for P-BCMA-101 to begin in the first half of 2019, with the goal of moving toward a potential biologics license application filing by the end of 2020 subject to positive data from such study,” continued Ostertag.
This open-label, multicenter, single-ascending dose, Phase 1 study is designed to assess the safety of P-BCMA-101 in up to 40 subjects with relapsed and/or refractory multiple myeloma. The primary objective of this study is to determine the safety and maximum-tolerated dose of P-BCMA-101. Secondary objectives include anti-myeloma effect of P-BCMA-101. This study is funded in part by the California Institute for Regenerative Medicine. Additional information about the Phase 1 clinical study of P-BCMA-101 is available at www.clinicaltrials.gov using identifier: NCT03288493
P-BCMA-101 is an autologous CAR-T therapeutic candidate being developed to treat patients with relapsed/refractory multiple myeloma. P-BCMA-101 targets cells that express B cell maturation antigen, or BCMA, which is expressed on essentially all multiple myeloma cells. P-BCMA-101 is engineered with Poseida’s non-viral piggyBac™ DNA Modification System, resulting in a high percentage of T stem cell memory cells. Preliminary results from the company’s ongoing Phase 1 clinical trial suggest that P-BCMA-101 may have improved response rates with a favorable safety profile compared to published results from clinical trials of other CAR-T therapies at similar doses. The Phase 1 study is funded in part by the California Institute for Regenerative Medicine.
About Poseida Therapeutics, Inc.
Poseida Therapeutics is a clinical-stage biotechnology company leveraging proprietary next-generation non-viral, gene engineering technologies to create life-saving therapeutics for patients with high unmet medical need. The company is developing a wholly-owned pipeline of autologous and allogeneic CAR-T product candidates, initially focused on the treatment of hematological malignancies and solid tumors. Poseida’s product candidates are designed to address the limitations of other CAR-T therapies, including duration of response, the ability to treat solid tumors and safety concerns. P-BCMA-101 is Poseida’s lead CAR-T product candidate, currently in Phase 1 clinical development for the treatment of relapsed/refractory multiple myeloma.
VP, Corporate Affairs
Poseida Therapeutics, Inc.