New CAR T-Cell P-PSMA-101 therapy shows promise in mCRPC

P-PSMA-101, an autologous CAR-T product for the treatment of metastatic castration-resistant prostate cancer (mCRPC), produces a long-lasting response, according to a press release from Poseida Therapeutics.1

Preclinical studies have shown that P-PSMA-101 clears tumor cells to an undetectable level in 100% of the levels with a single reported incidence of relapse at a lower dose. According to Poseida, no other product candidate has shown complete elimination of solid tumors in the clinical model, according to the developer.2 The full study results (NCT04249947) will be presented at the 6th annual CAR-TCR summit.

“We are excited about the preliminary data from our Phase 1 trial of P-PSMA-101, which provides further evidence of the effectiveness of our CAR-T platform for solid tumor cancers,” said Eric Ostertag, MD, PhD, Managing Director of Poseida, in a press release. “To date, other CAR-T therapies have not had much success apart from hematologic malignancies. The deep and long-lasting responses from our trial demonstrate that CAR-T products have the potential to work well against solid tumors, even at low doses, when using the correct technology platform. “

The phase 1 study has an estimated enrollment of 40 participants and an estimated completion date of September 2036. Primary endpoints include the safety of P-PSMA-101, the maximum tolerated dose, and the efficacy of agent up to 15 years.3

The study followed a 3 + 3 dose escalation cohort of single and multiple doses of P-PSMA-101. The study was divided into 4 parts. In part 1a, patients received a single dose of P-PSMA. In part 1b, patients received multiple doses of the agent. In part 1c, patients received a single infusion of P-PSMA-101. In part 1d, patients received multiple doses. In all cohorts, P-PSMA was administered followed by a conditioning regimen of chemotherapy. In each arm, rimiducid can be given as directed.

The first results announced that 9 patients with mCRPC have been recruited. Of these 9 patients, 5 received a single treatment of 0.25 x 10E6 cells / kg and 4 patients received a single dose of 0.75 x 10E6 cells / kg. All 9 patients were pretreated, with an average of 6 prior lines of treatment since the median time of diagnosis 6.4 years ago.

Of the 9 patients treated, 5 presented measurable reductions in PSA levels, 3 patients presented with more than 50% reduction in PSA levels and concordant improvements in PSMA-PET imaging. One patient has shown signs of complete tumor removal and remains in a sustained response more than 5 months later.

P-PSMA has been shown to be well tolerated, with only 3 cases of cytokine release syndrome observed. All cases were grade 1/2 and were treated with early treatment. No cases of neurotoxicity have been reported at the data cut-off date.

“We believe that the key to success in solid tumors is a product with a high percentage of desirable memory T-stem cells (Tscms),” said Matthew Spear, MD, medical director of Poseida in a press release. “In this study, we demonstrated that a high percentage Tscm CAR-T product can harbor the bone marrow and, in at least one case, completely eliminate the tumor. This bone marrow rallying property may be particularly important for bone-affecting diseases such as adenocarcinoma of the prostate. It is important to note that the favorable tolerance associated with our Tscm CAR-T products has extended to prostate cancer where we have so far observed a manageable cytokine release syndrome and no neurotoxicity. “

To participate in the study, patients must be male, 18 years of age or older, have confirmed mCRPC, measurable disease, adequate organ function, and an ECOG score of 0 or 1. Patients with inadequate venous access or contradictions to leukopheresis, second active malignancy, history of central nervous system disease, active infection, received anti-cancer drugs within 2 weeks of starting treatment, received immunosuppressive drugs within 2 weeks following the start of treatment, or liver metastases are not eligible to participate.

The study is currently recruiting from California, Colorado, Massachusetts and New York.

THE REFERENCES:
1.Poseida Therapeutics presents the preliminary results of the Phase 1 trial of P-PSMA-101 at the 6th Annual CAR-TCR Summit. Press release. Therapeutic Poseida. August 31, 2021. Accessed September 1, 2021. https://bit.ly/3kGl1iJ
2.Pipeline. Therapeutic Poseida. Accessed September 1, 2021. https://bit.ly/3DGcTHM.
3. CAR-T P-PSMA-101 cells for the treatment of subjects with metastatic castration resistant prostate cancer (mCRPC). ClinicalTrials.gov. Accessed September 1, 2021. https://bit.ly/2WKIOWz.


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