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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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)

Conditions
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Prostate Cancer, Prostatic Neoplasms, Castration-Resistant, Neoplasms by Histologic Type, Neoplasms, Prostate, Metastatic Castration-resistant Prostate Cancer, Neoplasms, Prostatic Neoplasms, Genital Neoplasms, Male, Urogenital Neoplasms, Neoplasms by Site, Prostatic Disease, Salivary Gland Cancer, Salivary Gland Tumor, Adenoid Cystic Carcinoma, Salivary Duct Carcinoma, Mucoepidermoid Carcinoma, Acinic Cell Tumor

Intervention / Treatment
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* Biological: P-PSMA-101 CAR-T cells
* Drug: Rimiducid


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Open label, 3 + 3 design of dose-escalating cohorts with open label, dose expansion at RP2D
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: P-PSMA-101 CAR-T cells (Single Dose - Part 1a)<br>Single ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following conditioning chemotherapy regimen A. Rimiducid may be administered as indicated. | Biological: P-PSMA-101 CAR-T cells<br>* 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).<br>Drug: Rimiducid<br>* Rimiducid (safety switch activator) may be administered as indicated<br>|
| Experimental: P-PSMA-101 CAR-T cells (Multiple Dose - Part 1b)<br>Cyclic administration of ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following conditioning chemotherapy regimen A. Rimiducid may be administered as indicated. | Biological: P-PSMA-101 CAR-T cells<br>* 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).<br>Drug: Rimiducid<br>* Rimiducid (safety switch activator) may be administered as indicated<br>|
| Experimental: P-PSMA-101 CAR-T cells (Single Dose - Part 1c)<br>Single ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following conditioning chemotherapy regimen B. Rimiducid may be administered as indicated. | Biological: P-PSMA-101 CAR-T cells<br>* 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).<br>Drug: Rimiducid<br>* Rimiducid (safety switch activator) may be administered as indicated<br>|
| Experimental: P-PSMA-101 CAR-T cells (Multiple Dose - Part 1d)<br>Cyclic administration of ascending dose cohorts, given via intravenous infusions of CAR-T cells, following conditioning chemotherapy regimen B. Rimiducid may be administered as indicated. | Biological: P-PSMA-101 CAR-T cells<br>* 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).<br>Drug: Rimiducid<br>* Rimiducid (safety switch activator) may be administered as indicated<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the Safety of P-PSMA-101 | Incidence and severity of treatment-emergent adverse events | Baseline through 15 years | 
| Determine the maximum tolerated dose of P-PSMA-101 | Rate of dose limiting toxicities (DLT) | Baseline through Day 28 | 
| Assess the efficacy of P-PSMA-101 (ORR) | 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). | Baseline through 15 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CAR-T cells, metastatic castration-resistant prostate cancer (mCRPC)