P-PSMA-101 CAR-T Cells in the Treatment of Subjects With Metastatic Castration-Resistant Prostate Cancer (mCRPC)

• ClinicalTrials.gov Identifier: NCT04249947
• Recruitment Status: Recruiting
• First Posted: January 31, 2020
• Last Update Posted: January 6, 2021
• Sponsor: Poseida Therapeutics, Inc.
• Information provided by (Responsible Party): Poseida Therapeutics, Inc.

Tracking Information

• First Submitted Date: January 28, 2020
• First Posted Date: January 31, 2020
• Last Update Posted Date: January 6, 2021
• Actual Study Start Date: February 28, 2020
• Estimated Primary Completion Date: September 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 29, 2020)

• Assess the Safety of P-PSMA-101 [ Time Frame: Baseline through 15 years ]
  Incidence and severity of treatment-emergent adverse events
• Determine the maximum tolerated dose of P-PSMA-101 [ Time Frame: Baseline through Day 28 ]
  Rate of dose limiting toxicities (DLT)
• Assess the efficacy of P-PSMA-101 (ORR) [ Time Frame: Baseline through 15 years ]
  According to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 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).

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: P-PSMA-101 CAR-T Cells in the Treatment of Subjects With Metastatic Castration-Resistant Prostate Cancer (mCRPC)
• Official Title: A Phase 1 Dose Escalation and Expanded Cohort Study of P-PSMA-101 in Subjects With 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.

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 Type: Interventional
• Study Phase: Phase 1

Study Design

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 RP2D

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

• 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

Intervention

• 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

Study Arms

• 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.
  Interventions:

  • Biological: P-PSMA-101 CAR-T cells
  • Drug: Rimiducid
• 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.
  Interventions:

  • Biological: P-PSMA-101 CAR-T cells
  • Drug: Rimiducid
• 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.
  Interventions:

  • Biological: P-PSMA-101 CAR-T cells
  • Drug: Rimiducid
• 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.
  Interventions:

  • Biological: P-PSMA-101 CAR-T cells
  • Drug: Rimiducid

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 29, 2020): 40
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 2036
• Estimated Primary Completion Date: September 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Males ≥18 years of age
• Must have a confirmed diagnosis of mCRPC
• Must have measurable disease by RECIST 1.1 or bone only metastases with measurable PSA (≥1 ng/mL)
• Must have progressed by PCWG3 and/or RECIST 1.1
• 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, 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 or 5 half-lives (whichever is longer) 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
• Has a history of or known predisposition to HLH or MAS

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Angie Schinkel; 858 779 3103; clinicaltrials@poseida.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04249947
• Other Study ID Numbers: P-PSMA-101-001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Poseida Therapeutics, Inc.
• Study Sponsor: Poseida Therapeutics, Inc.
• Collaborators: Not Provided

Investigators

• Study Director: Boyan Litchev, M.D.; Sponsor Executive Medical Director

• PRS Account: Poseida Therapeutics, Inc.
• Verification Date: January 2021