The early-phase data readout follows news that the FDA recently approved its IND for its CAR-T candidate in multiple myeloma.
Data presented at the 2021 CAR-TCR Summit demonstrated early measures of success in Poseida Therapeutics’ phase 1 clinical trial (NCT04249947) of P-PSMA-101, its solid tumor autologous CAR-T product candidate to treat patients with metastatic castrate-resistant prostate cancer (mCRPC).1
The promising data puts Poseida a step ahead as cell therapy companies scramble to transfer their success in liquid tumors to more difficult targets in solid tumors.
Among the 9 patients enrolled, 5 showed measuable declines in prostate-specific antigen (PSA) levels; 3 showed a greater than 50% decline in PSA levels and showed concordant improvements in prostate-specific membrane antigen (PSMA)-PET imaging; and 1 patient showed evidence of complete tumor elimination, with a durable response of more than 5 months currently.
“This is the first time that I have seen such impressive responses with an immunotherapy product,” said Susan F. Slovan, MD, PhD, associate vice chair of academic administration at Memorial Sloan Kettering Cancer Center, and study investigator, in a statement.1 “The responses of my patients in the trial are far beyond my expectations.”
The phase 1, open-label, 3+3 dose-escalating study will assess the CAR-T therapy in up to 40 patients with mCRPC, with the main objectives to assess safety, efficacy, and maximum tolerated dose. Of the currently enrolled patients, 5 received a single low-dose (0.25X10E6 cells/kg) and 4 patients received a single high-dose (0.75X10E6 cells/kg). All patients underwent a lymphodepletion regimen prior to intravenous infusion of the autologous CAR-T cells, which target prostate cancer cells expressing the cell surface antigen PSMA.
Reported safety data showed 3 cases of possible low-grade cytokine release syndrome which were effectively managed with early treatment, and no cases of neurotoxicity at time of this presentation. The favorable safety and tolerability profile is a welcome relief for the company, which experienced a patient death early on due to macrophage activation syndrome, reportedly exacerbated by patient non-compliance. The death had resulted in the FDA placing a full clinical hold on the trial back in August 2020; the hold was lifted that November after Poseida “agreed to implement protocol amendments intended to increase patient compliance and safety that include modified inclusion and exclusion criteria and frequency of monitoring and laboratory testing.”2
“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.1 “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.”
The company is also making headway in other oncology targets with news that the FDA recently approved its investigational new drug application for its fully allogeneic CAR-T therapy for relapsed/refractory multiple myeloma.3
The agent, P-BCMA-ALLO1, has shown superiority in in vitro and in vivo preclinical studies compared with an autologous CAR-T therapy. The manufacturing of the allogeneic agent includes a “booster molecule” that helps improves expansion of gene-edited cells and allows for production of more patient doses from a single manufacturing run.
Dosing for the phase 1 study, P-BCMA-ALLO1-101, will begin later this year in a similar 3+3 dose escalation design in which patients will receive a single dose following a standard conditioning regimen. Safety, tolerability, and response will be assessed, with protocols allowing for additional dosing regimens and re-dosing once safety is established.