Acinic Cell Tumor, Adenoid Cystic Carcinoma, Genital Neoplasms, Male, Metastatic Castration-resistant Prostate Cancer, Mucoepidermoid Carcinoma, Neoplasms, Neoplasms by Histologic Type, Neoplasms by Site, Neoplasms, Prostate, Prostate Cancer, Prostatic Disease, Prostatic Neoplasms, Prostatic Neoplasms, Castration-Resistant, Salivary Duct Carcinoma, Salivary Gland Cancer, Salivary Gland Tumor, Urogenital Neoplasms
Conditions
Keywords
CAR-T cells, metastatic castration-resistant prostate cancer (mCRPC)
Brief summary
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.
Detailed description
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.
Interventions
BIOLOGICALP-PSMA-101 CAR-T cells
P-PSMA-101 is an autologous chimeric antigen receptor (CAR) T-cell therapy designed to target prostate cancer cells expressing the cell surface antigen prostate-specific membrane antigen (PSMA).
DRUGRimiducid
Rimiducid (safety switch activator) may be administered as indicated
Sponsors
Poseida Therapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open label, 3 + 3 design of dose-escalating cohorts with open label, dose expansion at RP2D
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assess the Safety of P-PSMA-101 | Baseline through 15 years | Incidence and severity of treatment-emergent adverse events |
| Determine the maximum tolerated dose of P-PSMA-101 | Baseline through Day 28 | Rate of dose limiting toxicities (DLT) |
| Assess the efficacy of P-PSMA-101 (ORR) | Baseline through 15 years | According to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, secondarily Immune Response Evaluation Criteria in Solid Tumors (iRECIST), and Prostate Cancer Response assessed by Prostate Cancer Working Group 3 (PCWG3) criteria: Overall Response Rate (ORR)-Percentage of patients with complete response (CR) or partial response (PR). |
Countries
United States
Outcome results
None listed