P-PSMA-101 CAR-T Cells in the Treatment of Subjects With Metastatic Castration-Resistant Prostate Cancer (mCRPC) and Advanced Salivary Gland Cancers (SGC)

A Phase 1 Dose Escalation and Expanded Cohort Study of P-PSMA-101 in Subjects With Metastatic Castration-Resistant Prostate Cancer (mCRPC) and Advanced Salivary Gland Cancers (SGC)

An open-label, multi-center, single and cyclic ascending dose study of P-PSMA-101 autologous CAR-T cells in patients with mCRPC and SGC.

This is an open label, multi-center Phase 1 study that will follow a 3 + 3 design of dose-escalating cohorts of single and multiple doses of P-PSMA-101 to determine a Recommended Phase 2 Dose (RP2D). Additional participants will be treated with P-PSMA-101 at the determined RP2D.

Following consent, enrolled participants will undergo a leukapheresis procedure to obtain peripheral blood mononuclear cells (PBMCs) which will be sent to a manufacturing site to produce P-PSMA-101 CAR-T cells. The cells will then be returned to the investigational site and administered after a lymphodepleting chemotherapy regimen. Rimiducid may be administered as indicated.

Inclusion Criteria:

• Subjects ≥18 years of age
• Must have a confirmed diagnosis of mCRPC or SGC
• Must have measurable disease by RECIST 1.1 or bone only metastases with measurable PSA (≥1 ng/mL) (mCRPC subjects only)
• Must have progressed by PCWG3 and/or RECIST 1.1 (mCRPC subjects only)
• Must be willing to practice birth control from screening and for 2 years after the last administration of P-PSMA-101
• Must have adequate vital organ function within pre-determined parameters
• Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

Exclusion Criteria:

• Has inadequate venous access and/or contraindications to leukapheresis
• Has an active second malignancy in addition to mCRPC or SGC, excluding low-risk neoplasms such as non-metastatic basal cell or squamous cell skin carcinoma
• Has a history of or active autoimmune disease
• Has a history of significant central nervous system (CNS) disease, such as stroke or epilepsy
• Has an active systemic (viral, bacterial or fungal) infection
• Has received anti-cancer medications (excluding GnRH targeted therapies) within 2 weeks of the time of initiating conditioning chemotherapy
• Has received immunosuppressive medications (including anti-cancer medications) within 2 weeks of initiating leukapheresis and/or expected to require them while enrolled in the study
• Has received systemic corticosteroid therapy within 2 weeks of either the required leukapheresis or is expected to require it during the course of the study
• Has CNS metastases or symptomatic CNS involvement
• Has a history of significant ocular disease
• Has a history of significant liver disease or active liver disease
• Has liver metastases (<5 lesions and maximum diameter </= 2.5 cm permitted)
• Has a history of or known predisposition to HLH or MAS