Preliminary findings indicate that P-PSMA-101, a CAR T-cell therapy, may be efficacious in patient with metastatic castration-resistant prostate cancer.
CAR T-cell therapy P-PSMA-101 yielded promising early data in a cohort of patients with metastatic castration-resistant prostate cancer (mCRPC), according to the preliminary findings from a phase 1 study (NCT04249947).
Study data, which were presented at the 6th Annual CAR-TCR Summit virtual meeting, indicated that 5 patients experienced a measurable decline in prostate-specific antigen (PSA), 3 of whom experienced a greater decline of more than 50% as well as concordant improvements identified through prostate-specific membrane antigen (PSMA)–PET imaging. Additionally, 1 patient had evidence of complete tumor elimination and continues to experience a durable response of more than 5 months as of the study’s presentation.
“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,” study presenter Eric Ostertag, MD, PhD, chief executive officer of Poseida, said 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 open-label, multi-center study utilizes a 3+3 design and features dose-escalating cohorts of single and multiple doses of P-PSMA-101 that will help to determine the recommended phase 2 dose. The trial has an estimated enrollment of 40 patients.
As of the trial’s cut-off date, a total of 9 patients with mCRPC have been enrolled on the study. Patients received 1 of 2 doses: 0.25 ×10E6 cells/kg (n = 5) or 0.75 × 10E6 cells/kg (n = 4). All patients underwent a lymphodepleting regimen that included a 30 mg/m2 dose of fludarabine plus a 300 mg/m2 dose of cyclophosphamide. The population of patients was heavily pre-treated, with investigators reporting a median of 6 prior lines of therapy and a median time since diagnosis of 6.4 years.
The primary outcome measures are safety, maximum tolerated dose, and efficacy, including overall response rate, complete response rate, and partial response rate.
Participants needed to be aged 18 years or older with a confirmed diagnosis of mCRPC. Disease needed to be measurable by RECIST 1.1 criteria or only have bone metastases with measurable PSA. Adequate organ function and an ECOG performance status of 0 or 1 were required.
“This innovative Poseida PSMA-directed CAR T cell platform has demonstrated a robust anti-tumor response in patients with metastatic castration resistant prostate cancer. This is the first time that I have seen such impressive responses with an immunotherapy product. The responses of my patients in the trial are far beyond my expectations,” trial investigator Susan F. Slovin, MD, PhD, associate vice chair of academic administration at Memorial Sloan Kettering Cancer Center, concluded.
Poseida Therapeutics presents preliminary results from phase 1 trial of P-PSMA-101 at the 6th Annual CAR-TCR Summit. News release. Poseida Therapeutics Inc. August 31, 2021. Accessed September 3, 2021. https://yhoo.it/3jE4MU2