Regenerative Medicine and Stem Cells Technologies

Poseida Therapeutics on Tuesday reported preliminary results from a Phase I trial of its experimental autologous CAR-T product P-PSMA-101 "confirming activity" in patients with metastatic castrate-resistant prostate cancer (mCRPC). "To date, other CAR-T therapeutics have not had much success outside of haematologic malignancies," remarked CEO Eric Ostertag, but the "deep and durable responses in our trial demonstrate that CAR-T products have the potential to work well against solid tumours, even at low doses, when using the appropriate technology platform."

Findings presented Tuesday at the annual CAR-TCR Summit were on the first nine patients enrolled at low-dose cohorts as of the cut-off date. Participants were heavily pre-treated, having received an average of six prior lines of therapy. Five patients received a single P-PSMA-101 treatment at a dose of 0.25x10E6 cells/kg, while four were given a single treatment of 0.75x10E6 cells/kg, following lymphodepletion with fludarabine plus cyclophosphamide.

Tumour 'completely' eliminated in one patient

Poseida said five patients dosed showed "measurable declines" in prostate-specific antigen (PSA) levels, while three had a ≥50% drop in PSA and concordant improvements in PSMA-PET imaging. In addition, Poseida said one patient showed "evidence of complete tumour elimination, and remains in a durable response of greater than five months." The ongoing dose-escalating trial is designed to recruit up to 40 adult subjects with mCRPC.

"We believe the key to success in solid tumours is a product with a high percentage of desirable stem-cell memory T cells (Tscm)," explained chief medical officer Matthew Spear, adding "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 tumour." He suggested this bone marrow "homing" property may be particularly key for bone-avid diseases such as prostate adenocarcinoma.

Follows trial halt last year

Spear also highlighted the "favourable" tolerability associated with Poseida's Tscm CAR-T products "[carrying] over to prostate cancer, where we have so far seen manageable cytokine release syndrome (CRS) and no neurotoxicity." Last year, the FDA placed the study on clinical hold following the death of a participant who had developed macrophage activation syndrome (MAS). The hold was lifted in November after some protocol amendments. Aside from the MAS case, which Poseida said had been exacerbated by patient non-compliance, the company on Tuesday also reported three cases of possible CRS, which were "all low-grade and managed well with early treatment."

Meanwhile, earlier this week, Poseida announced that the FDA had cleared its investigational new drug application for P-BCMA-ALLO1, its first fully allogeneic CAR-T candidate for patients with relapsed/refractory multiple myeloma. The company says it is now focused on opening clinical sites with the aim of beginning dosing of P-BCMA-ALLO1 later this year.

https://www.firstwordpharma.com/node/1859784?tsid=28&region_id=6