Poseida’s CAR T-Cell Therapy IND Accepted for Solid Tumors

Poseida’s announcement follows their presentation of positive data in metastatic castrate-resistant prostate cancer in September 2021.

The FDA has cleared Poseida Therapeutics’ investigational new drug (NDA) application for the allogeneic chimeric antigen receptor (CAR) T-cell therapy P-MUC1C-ALLO1 targeting multiple solid tumors.1

"We are excited to begin the P-MUC1C-ALLO1 trial, an evaluation of a fully allogeneic CAR-T product candidate with the potential to treat a wide range of solid tumors, including breast, ovarian and other cancers," Eric Ostertag, MD, PhD, chief executive officer, Poseida Therapeutics, said in a statement.1 "The genetic edits in P-MUC1C-ALLO1 have been shown to reduce or fully eliminate alloreactivity, and our proprietary manufacturing process, which includes our booster molecule, has the potential to treat many patients from a single manufacturing run. We look forward to beginning this trial and to presenting initial clinical data in 2022."

A multi-center, open-label, phase 1 study will be conducted in adults with refractory locally-advanced or metastatic epithelial-derived solid tumors. The study will evaluate P-MUC1C-ALLO1's safety, tolerability, and preliminary efficacy in dose-escalating cohorts with a 3+3 design. Participants will receive P-MUC1C-ALLO1 allogeneic CAR-T cells following a standard conditioning regimen. The study may evaluate additional dosing regimens after initial safety has been established.

P-MUC1C-ALLO1 is being explored in breast, colorectal, lung, ovarian, pancreatic, and renal cancers, as well as other cancers expressing MUC1C. P-MUC1C-ALLO1 previously demonstrated efficacy in preclinical trials in which investigators observed elimination of tumor cells to undetectable levels in models of both triple-negative breast and ovarian cancer.

READ MORE: IND Accepted for Sickle Cell Disease Cell Therapy

Poseida Therapeutics previously received IND clearance for another allogeneic CAR T-cell therapy, P-BCMA-ALLO1, for the treatment of relapsed/refractory multiple myeloma.2 The therapy showed superiority to an autologous CAR-T therapy in preclinical studies and is being evaluated in a similar phase 1 study (NCT04960579). P-BCMA-ALLO1 includes a unique “booster molecule” that helps improves expansion of gene-edited cells and allows for production of more patient doses from a single manufacturing run.

Poseida presented data from the phase 1 study (NCT04249947) of an autologous CAR T-cell therapy, P-PSMA-101, for the potential treatment of metastatic castrate-resistant prostate cancer (mCRPC) at the 2021 CAR-TCR Summit in September.3 

Investigators observed measurable declines in prostate-specific antigen (PSA) levels in 5 of 9 patients enrolled, 3 of which had over a 50% decline in PSA levels. Concordant improvements in prostate-specific membrane antigen (PSMA)-PET imaging were also observed and 1 patient showed evidence of complete tumor elimination, with a durable response of over 5 months as of the data presentation.

“This is the first time that I have seen such impressive responses with an immunotherapy product,” study investigator Susan F. Slovan, MD, PhD, associate vice chair, academic administration, Memorial Sloan Kettering Cancer Center, said in an earlier statement.3 “The responses of my patients in the trial are far beyond my expectations.”

REFERENCES
1. Poseida Therapeutics announces FDA clearance of investigational new drug application for P-MUC1C-ALLO1, a fully allogeneic CAR-T targeting multiple solid tumors. News release. Poseida Therapeutics. December 20, 2021. https://www.biospace.com/article/releases/poseida-therapeutics-announces-fda-clearance-of-investigational-new-drug-application-for-p-muc1c-allo1-a-fully-allogeneic-car-t-targeting-multiple-solid-tumors/
2. Poseida Therapeutics Announces FDA Clearance of Investigational New Drug Application for P-BCMA-ALLO1, an Allogeneic CAR-T Candidate for Relapsed/Refractory Multiple Myeloma. News release. Poseida Therapeutics. August 30, 2021. https://investors.poseida.com/news-releases/news-release-details/poseida-therapeutics-announces-fda-clearance-investigational-new
3. Poseida Therapeutics Presents Preliminary Results from Phase 1 Trial of P-PSMA-101 at the 6th Annual CAR-TCR Summit. News release. Poseida Therapeutics. August 31, 2021. https://investors.poseida.com/news-releases/news-release-details/poseida-therapeutics-presents-preliminary-results-phase-1-trial 
4. Poseida Therapeutics Announces Clinical Hold Lifted on Phase I Autologous CAR-T Study in Prostate Cancer. News release. Poseida Therapeutics. November 2, 2020. https://www.prnewswire.com/news-releases/poseida-therapeutics-announces-clinical-hold-lifted-on-phase-i-autologous-car-t-study-in-prostate-cancer-301164397.html