On April 8, 2024 Poseida Therapeutics, Inc. (Nasdaq: PSTX), a clinical-stage cell and gene therapy company advancing a new class of treatments for patients with cancer and rare diseases, reported new data from a subset of patients in an ongoing Phase 1 study of its lead program, P-BCMA-ALLO1 (Press release, Poseida Therapeutics, APR 8, 2024, View Source [SID1234641877]). Results showed that three of the five (60%) patients with relapsed/refractory multiple myeloma who had progressed following BCMA-targeted therapy achieved clinical responses with P-BCMA-ALLO1. In addition, this investigational treatment was well-tolerated.

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P-BCMA-ALLO1 is a novel investigational B-cell maturation antigen (BCMA)-targeted allogeneic, T stem cell memory (TSCM)-rich chimeric antigen receptor T-cell (CAR-T) therapy manufactured from healthy donor T-cells and available off-the-shelf. These new Phase 1 study subgroup data and a new data analysis of different lymphodepletion regimens in patients treated with P-BCMA-ALLO1 for multiple myeloma or P-MUC1C-ALLO1 for solid tumors are being presented today in a poster session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024 in San Diego.

"Multiple myeloma remains incurable, and patients often relapse, despite initial high response rates with BCMA-targeted immunotherapies, including autologous CAR-T therapies," said Bhagirathbhai Dholaria, M.D., Associate Professor of Medicine (Hematology/Oncology) at the Vanderbilt-Ingram Cancer Center in Nashville, Tenn. "New treatment options are urgently needed for these patients, which is why I’m encouraged by these impressive Phase 1 subgroup results, which may be the first report of an allogeneic CAR-T therapy showing clinical activity in heavily pretreated patients whose myeloma has progressed after multiple BCMA-targeted immunotherapies."

"These new data build on the P-BCMA-ALLO1 data presented at ASH (Free ASH Whitepaper) 2023, which demonstrated a 100% overall response rate in patients who had not been previously treated with a BCMA-targeted therapy. The new findings also provide additional evidence that our investigational, off-the-shelf allogeneic CAR-T therapy could be an appropriate treatment for a broader range of patients with multiple myeloma, including those with relapsed/refractory disease whose cancer progressed following prior BCMA-targeted therapy, representing the highest unmet need in this setting," said Syed Rizvi, M.D., Chief Medical Officer at Poseida. "In addition, we continue to explore the optimal lymphodepletion regimen for CAR-T in solid tumors and are directly applying these learnings to our P-MUC1C-ALLO1 trial with the goal of delivering the same benefits in solid tumors as we have seen in myeloma. We look forward to sharing more fulsome datasets on both our BCMA and MUC1-C programs in the second half of 2024."

New Phase 1 P-BCMA-ALLO1 Study Subgroup Data

The open-label, multicenter Phase 1 dose-escalation study in patients with relapsed/refractory multiple myeloma is assessing the safety and maximum tolerated dose of P-BCMA-ALLO1 (primary objective) and its anti-myeloma activity (secondary objective). Study participants were required to have received a prior proteasome inhibitor, immunomodulatory drug and anti-CD38 monoclonal antibody. Five study participants who had progressed on or following prior BCMA-targeting autologous CAR-T, T-cell engagers or both, and with ninety days post-P-BCMA-ALLO1 treatment follow-up, are presented in this poster.

Key findings from the subgroup analysis showed that P-BCMA-ALLO1 was well tolerated with no dose-limiting toxicities, graft vs. host disease, or Grade 3 or greater cytokine release syndrome (CRS) or immune effector cell neurotoxicity syndrome (ICANS). The overall response rate in patients receiving P-BCMA-ALLO1 was 60%, with all three patients who achieved a clinical response experiencing a very good partial response (VGPR). This included one patient who had previously received both teclistamab and an autologous CAR-T therapy and has maintained a response for more than four months.

New Data on Optimizing Lymphodepletion (LD) Regimen for Patients with Solid Tumors Treated with Investigational Allogeneic CAR-T Therapy

As patients with multiple myeloma receive more bone marrow suppressive treatments than those with solid tumors during their treatment journeys, this analysis evaluated the effect of increasing amounts of cyclophosphamide in LD regimens to optimize CAR-T pharmacokinetics.

The analysis compared various LD regimens in two early Phase 1 trials of Poseida’s investigational allogeneic CAR-T cell therapies in patients with multiple myeloma and solid tumors. Results showed that patients with solid tumors may require higher cyclophosphamide doses to achieve adequate LD, which would provide a sufficient niche to support allogeneic CAR-T expansion.

Poster Presentation Details

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Clinical Activity of P-BCMA-ALLO1, a B-cell Maturation Antigen (BCMA) Targeted Allogeneic Chimeric Antigen Receptor T-cell (CAR-T) Therapy, in Relapsed Refractory Multiple Myeloma (RRMM) Patients Following Progression on Prior BCMA Targeting Therapy CT071 Rajesh Belani, M.D., Clinical Development, Poseida Therapeutics Phase I Clinical Trials 1 Monday, April 8, 9:00 a.m.-12:30 p.m. PT Poster section 48, Poster board 21
Solid Tumor Patients Require Higher Cyclophosphamide Dose than Multiple Myeloma Patients to Achieve Adequate Lymphodepletion Necessary to Enable Allogeneic CAR-T Expansion CT070 Sabrina Haag, Ph.D., Translational Medicine, Poseida Therapeutics Phase I Clinical Trials 1 Monday, April 8, 9:00 a.m.-12:30 p.m. PT Poster section 48, Poster board 20
About P-BCMA-ALLO1

P-BCMA-ALLO1 is an investigational allogeneic CAR-T therapy licensed to Roche that targets B-cell maturation antigen (BCMA) and is in Phase 1 clinical development for the treatment of patients with relapsed/refractory multiple myeloma. This allogeneic program includes a VH-based binder that targets BCMA. Phase 1 clinical data presented at ASH (Free ASH Whitepaper) 2023 supports the Company’s belief that TSCM-rich allogeneic CAR-Ts have the potential to offer effective, safe and reliable treatment addressing unmet needs in multiple myeloma. The U.S. Food and Drug Administration granted Orphan Drug Designation to P-BCMA-ALLO1 for the treatment of multiple myeloma. Additional information about the Phase 1 study is available at www.clinicaltrials.gov (NCT04960579).

About P-MUC1C-ALLO1

P-MUC1C-ALLO1 is an investigational allogeneic CAR-T therapy in Phase 1 clinical development for multiple solid tumor indications. Poseida believes P-MUC1C-ALLO1 has the potential to treat a wide range of solid tumors derived from epithelial cells, such as breast, ovarian, colorectal, lung, pancreatic and renal cancers, as well as other cancers expressing a cancer-specific form of the Mucin 1 protein (MUC1-C). P-MUC1C-ALLO1 is designed to be fully allogeneic, with genetic edits to eliminate or reduce both host-vs-graft and graft-vs-host alloreactivity. Poseida has demonstrated the elimination of tumor cells to undetectable levels in preclinical models of both breast and ovarian cancer. Additional information about the Phase 1 study is available at www.clinicaltrials.gov (NCT05239143).