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

Phase 1

Active, not recruiting

• Conditions: Acinic Cell Tumor; Neoplasms by Histologic Type; Neoplasms, Prostate; Neoplasms; Prostate Cancer; Metastatic Castration-resistant Prostate Cancer; Prostatic Neoplasms, Castration-Resistant; Genital Neoplasms, Male; Prostatic Neoplasms; Urogenital Neoplasms
• Interventions: Biological: P-PSMA-101 CAR-T cells; Drug: Rimiducid

• Registration Number: NCT04249947
• Lead Sponsor: Poseida Therapeutics, Inc.

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.

Study Timeline

• Study First Submitted: 2020-01-28
• Study First Submitted QC: 2020-01-29
• Study First Posted: 2020-01-31
• Study Start: 2020-02-28
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-17
• Last Update Posted: 2024-04-18
• Primary Completion: 2024-10
• Study Completion: 2036-09

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 60

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

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
P-PSMA-101 CAR-T cells (Single Dose - Part 1a)	P-PSMA-101 CAR-T cells	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.
P-PSMA-101 CAR-T cells (Multiple Dose - Part 1b)	P-PSMA-101 CAR-T cells	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.
P-PSMA-101 CAR-T cells (Single Dose - Part 1c)	P-PSMA-101 CAR-T cells	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.
P-PSMA-101 CAR-T cells (Multiple Dose - Part 1d)	P-PSMA-101 CAR-T cells	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.
P-PSMA-101 CAR-T cells (Multiple Dose - Part 1b)	Rimiducid	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.
P-PSMA-101 CAR-T cells (Multiple Dose - Part 1d)	Rimiducid	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.
P-PSMA-101 CAR-T cells (Single Dose - Part 1a)	Rimiducid	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.
P-PSMA-101 CAR-T cells (Single Dose - Part 1c)	Rimiducid	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.

Primary Outcome Measures

Name	Time	Method
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).

Trial Locations

Locations (10)

University of California San Diego; 🇺🇸 San Diego, California, United States

University of California San Francisco; 🇺🇸 San Francisco, California, United States

Dana-Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

City of Hope Comprehensive Cancer Center; 🇺🇸 Duarte, California, United States

University of Maryland, Baltimore; 🇺🇸 Baltimore, Maryland, United States

Tennessee Oncology; 🇺🇸 Nashville, Tennessee, United States

Sarah Cannon Research Institute at HealthONE; 🇺🇸 Denver, Colorado, United States

Tulane University Hospital and Clinic; 🇺🇸 New Orleans, Louisiana, United States