P-PSMA-101, an autologous CAR-T product for the treatment of metastatic castrate-resistant prostate cancer, produces a durable response.
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 Poseida Therapeutics.1
Preclinical studies have found that P-PSMA-101 eliminates tumor cells to an undetectable level in 100% of levels with only one reported incidence of relapse at a lower dose. According to Poseida, no other product candidate has shown a complete solid tumor elimination in the clinical model, according to the developer.2 Full results of the study (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, chief executive officer of Poseida, 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 at low doses, when using the appropriate technology platform."
The phase 1 study has an estimated enrollment of 40 participants and an estimated completion date of September 2036. Primary end points include the safety of P-PSMA-101, maximum tolerated dose, and efficacy of the agent up to 15 years.3
The study followed a 3 + 3 dose-escalating cohorts of single and multiple P-PSMA-101 doses. The study was split into 4 parts. In the part 1a, patients fived 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 cohorts, P-PSMA was given followed by a chemotherapy conditioning regimen. In each arm, rimiducid may be administered as indicated.
Topline results announced that 9 patients with mCRPC have been enrolled. Of those 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 therapy since the median time of diagnosis 6.4 years ago.
Of the 9 patients dosed, 5 showed measurable declines in PSA levels, with 3 patients showing a greater than 50% declines in PSA levels and concordant improvements in PSMA-PET imaging. One patient showed evidence of complete tumor elimination and remains 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 early treatment. No cases of neurotoxicity were reported at data cutoff.
"We believe the key to success in solid tumors is a product with a high percentage of desirable stem cell memory T cells (Tscm)," said Matthew Spear, MD, chief medical officer of Poseida in a press release. "In this study, we have demonstrated that a high-percentage Tscm CAR-T product can home to the bone marrow and, in at least one case, completely eliminate tumor. This bone marrow homing property may be particularly important for bone avid diseases such as prostate adenocarcinoma. Importantly, the favorable tolerability associated with our Tscm CAR-T products has carried over to prostate cancer where we have so far seen manageable cytokine release syndrome and no neurotoxicity."
In order 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 inadequate venous access or contradictions to leukapheresis, a second active malignancy, a history of central nervous system disease, active infection, have received anti-cancer medications within 2 weeks of treatment initiation, have received immunosuppressive medications within 2 weeks of treatment initiation, or liver metastases are not eligible to participate.
The study is currently recruiting in California, Colorado, Massachusetts, and New York.