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

Sponsor

Poseida Therapeutics, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04249947

Collaborator

(none)

Enrollment

Locations

Arms

198.1

Anticipated Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Prostatic Neoplasms, Castration-Resistant Neoplasms by Histologic Type Neoplasms, Prostate Prostate Cancer 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	Biological: P-PSMA-101 CAR-T cells Drug: Rimiducid	Phase 1

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Intervention Model Description:

Open label, 3 + 3 design of dose-escalating cohorts with open label, dose expansion at RP2DOpen label, 3 + 3 design of dose-escalating cohorts with open label, dose expansion at RP2D

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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)

Actual Study Start Date :

Feb 28, 2020

Anticipated Primary Completion Date :

Sep 1, 2023

Anticipated Study Completion Date :

Sep 1, 2036

Arms and Interventions

Arm	Intervention/Treatment
Experimental: P-PSMA-101 CAR-T cells (Single Dose - Part 1a) 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 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). Drug: Rimiducid Rimiducid (safety switch activator) may be administered as indicated
Experimental: P-PSMA-101 CAR-T cells (Multiple Dose - Part 1b) 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 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). Drug: Rimiducid Rimiducid (safety switch activator) may be administered as indicated
Experimental: P-PSMA-101 CAR-T cells (Single Dose - Part 1c) 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 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). Drug: Rimiducid Rimiducid (safety switch activator) may be administered as indicated
Experimental: P-PSMA-101 CAR-T cells (Multiple Dose - Part 1d) 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 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). Drug: Rimiducid Rimiducid (safety switch activator) may be administered as indicated

Outcome Measures

Primary Outcome Measures

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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010
2	University of California San Diego	San Diego	California	United States	92093
3	University of California San Francisco	San Francisco	California	United States	94143
4	Sarah Cannon Research Institute at HealthONE	Denver	Colorado	United States	80218
5	Tulane University Hospital and Clinic	New Orleans	Louisiana	United States	70112
6	University of Maryland, Baltimore	Baltimore	Maryland	United States	21201
7	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
8	Massachusetts General Hospital	Boston	Massachusetts	United States	02215
9	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
10	Tennessee Oncology	Nashville	Tennessee	United States	37203