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

• ClinicalTrials.gov Identifier: NCT04249947
• Recruitment Status: Active, not recruiting
• First Posted: January 31, 2020
• Last Update Posted: November 17, 2022
• 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: November 17, 2022
• 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: December 21, 2021)

• 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, 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).

Original 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).

• 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) and Advanced Salivary Gland Cancers (SGC)
• 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)
• 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 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
• Salivary Gland Cancer
• Salivary Gland Tumor
• Adenoid Cystic Carcinoma
• Salivary Duct Carcinoma
• Mucoepidermoid Carcinoma
• Acinic Cell Tumor

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: Active, not recruiting
• Estimated Enrollment (submitted: November 3, 2021): 60
• Original Estimated Enrollment (submitted: January 29, 2020): 40
• Estimated Study Completion Date: September 2036
• Estimated Primary Completion Date: September 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• 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

• Current Responsible Party: Poseida Therapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Poseida Therapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Rajesh Belani, M.D.; Sponsor Executive Medical Director

• PRS Account: Poseida Therapeutics, Inc.
• Verification Date: November 2022