P-PSMA-101, an autologous CAR-T product for the treatment of metastatic castrate-resistant prostate cancer (mCRPC), produces a durable response, according to a news release by Posida Therapeutics.1
Preclinical studies have found that p-PSMA-101 eliminates tumor cells in 100% of the levels to an undetectable level, with only one reported event at low doses. According to Posida, no other product candidate has shown complete solid tumor eradication in clinical models, according to the developer. The full results of the study (NCT04249947) will be presented at the sixth 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, principal said the executive officer of Posida, in a press release. “To date, other CAR-T therapeutics have not had much success outside of hematologic malignancies. The deep and durable responses in our trial demonstrate that CAR-T products have the potential to work well against solid tumors, even that the appropriate technology platform when using, at a lower dosage.”
The Phase 1 study has an estimated enrollment of 40 participants and an estimated end date of September 2036. Primary end points included the safety of p-PSMA-101, the maximum tolerated dose, and the agent’s efficacy for up to 15 years.3
The study followed 3+3 dose escalation groups of single and multiple p-PSMA-101 doses. The study was divided into 4 parts. In Part 1a, patients took a single dose of p-PSMA. In Part 1B, patients received multiple doses of the agent. In Part 1c, patients were given a single infusion of P-PSMA-101. In Part 1d, patients received multiple doses. In all groups, p-PSMA was given after the chemotherapy conditioning regimen. In each arm, remiducid may be administered as indicated.
Topline results announced that 9 patients with mCRPC were enrolled. Of those 9 patients, 5 received a single dose 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 since the median time of diagnosis 6.4 years ago, with an average of 6 prior lines of therapy.
Of the 9 patients, 5 showed a measurable drop in PSA levels, 3 patients showed a more than 50% drop in PSA levels and concurrent improvement in PSMA-PET imaging. One patient showed evidence of complete tumor eradication and persisted in a durable response more than 5 months later.
P-PSMA was found to be well tolerated, with only 3 observed cases of cytokine release syndrome. All cases were grade 1/2 and were managed with initial treatment. No cases of neurotoxicity were reported at the data cutoff.
“We believe that the key to success in solid tumors is a product with a high percentage of desirable stem cell memory T cells (TSCM),” said Matthew Speer, Posida’s chief medical officer, in a press release. “In this study, we have shown that a high-percentage Tscm CAR-T product can be homing to the bone marrow and, in at least one case, can completely eradicate tumors. This bone marrow homing property is specific. Importantly, the favorable tolerability associated with our Tscm CAR-T products has led to prostate cancer, where we observed a manageable cytokine release syndrome so far. and has no neurotoxicity.”
To participate in the study, patients must be male and 18 years of age or older, have confirmed mCRPC, measurable disease, adequate organ function, and an ECOG score of 0 or 1. Patients with insufficient venous access or contraindications to leukapheresis, a second active malignancy, history of central nervous system disease, active infection, have received anticancer drugs within 2 weeks of initiation of treatment, immunosuppressants within 2 weeks of initiation of treatment Have received medications, or have liver metastases not eligible to participate.
The study is currently recruiting in California, Colorado, Massachusetts and New York.