P-MUC1C-ALLO1 Allogeneic CAR-T Cells in the Treatment of Subjects With Advanced or Metastatic Solid Tumors

Phase 1

Recruiting

• Conditions: Breast Cancer; Non Small Cell Lung Cancer; Colorectal Cancer; Pancreatic Cancer; Nasopharyngeal Cancer; Ovarian Cancer; Head and Neck Squamous Cell Carcinoma; Renal Cell Carcinoma; Gastric Cancer
• Interventions: Biological: P-MUC1C-ALLO1 CAR-T cells; Drug: Rimiducid

• Registration Number: NCT05239143
• Lead Sponsor: Poseida Therapeutics, Inc.

Brief Summary

A Phase 1, open label, dose escalation and expanded cohort study of P-MUC1C-ALLO1 in adult subjects with advanced or metastatic epithelial derived solid tumors, including but not limited to the tumor types listed below.

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-MUC1C-ALLO1 to determine a Recommended Phase 2 Dose (RP2D). P-MUC1C-ALLO1 is an allogeneic chimeric antigen receptor (CAR) T cell therapy designed to target cancer cells expressing Mucin1 cell surface associated C-Terminal (MUC1-C) antigen. Additional participants will be treated with P-MUC1C-ALLO1 at the determined RP2D.

Following enrollment, subjects will be treated with P-MUC1C-ALLO1 and will undergo serial measurements of safety, tolerability and response. Rimiducid may be administered as indicated.

Study Timeline

• Study First Submitted: 2022-02-03
• Study First Submitted QC: 2022-02-03
• Study First Posted: 2022-02-14
• Study Start: 2022-02-15
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-19
• Last Update Posted: 2024-04-23
• Primary Completion: 2026-04
• Study Completion: 2039-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• Males or females, Subjects ≥18 years with life expectancy >3 months
• Must have a confirmed diagnosis of unresectable, locally advanced or metastatic epithelial-derived cancer, refractory to standard of care therapy or ineligible or refused other existing treatment options
• Must have progressed during or after last therapy and have measurable disease
• Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 or Karnofsky performance status ≥70%
• Must have adequate vital organ function within pre-determined parameters
• Must have archived tumor tissue available or consent to a biopsy collection
• Must be willing to practice birth control
• Must have a negative pregnancy test at screening and prior to initiating lymphodepletion chemotherapy or study drug administration
• Must have recovered from toxicities due to prior therapies

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Exclusion Criteria

• Has inadequate venous access
• Has an active second malignancy in addition to the studied malignancy, excluding low-risk neoplasms such as non-metastatic basal cell or squamous cell skin carcinoma
• Is pregnant or lactating
• Has a history of or active autoimmune disease
• Has a history of significant central nervous system (CNS) disease, such as stroke, epilepsy
• Has an active systemic (viral, bacterial, or fungal) infection
• Has New York Heart Association (NYHA) Class III or IV heart failure, unstable angina, or a history of myocardial infarction or significant arrhythmia
• Has any psychiatric or medical disorder that would preclude safe participation in and/or adherence to the protocol
• Has received anticancer medications within 2 weeks of the time of initiating conditioning chemotherapy
• Has received immunosuppressive medications within 2 weeks of administration of P-MUC1C-ALLO1, and/or expected to require them while enrolled in the study
• Has received systemic corticosteroid therapy within 1 week of the administration of P-MUC1C-ALLO1 or is expected to require it during the course of the study
• Has known CNS metastases or symptomatic CNS involvement
• Has a history of significant liver disease or active liver disease
• Has a history of known genetic predisposition to HLH/MAS

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
P-MUC1C-ALLO1 CAR-T cells (Single Dose - Arm A1)	Rimiducid	* Single ascending A1 dose cohorts, given in a single intravenous infusion of CAR-T cells, following lymphodepletion regimen 1. * Rimiducid may be administered as indicated.
P-MUC1C-ALLO1 CAR-T cells (Single Dose - Arm E)	P-MUC1C-ALLO1 CAR-T cells	* Single ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following assigned lymphodepletion regimen. * Rimiducid may be administered as indicated.
P-MUC1C-ALLO1 CAR-T cells (Single Dose - Arm A)	P-MUC1C-ALLO1 CAR-T cells	* Single ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following lymphodepletion regimen 1. * Rimiducid may be administered as indicated.
P-MUC1C-ALLO1 CAR-T cells (Single Dose - Arm A)	Rimiducid	* Single ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following lymphodepletion regimen 1. * Rimiducid may be administered as indicated.
P-MUC1C-ALLO1 CAR-T cells (Multiple Dose - Arm B)	P-MUC1C-ALLO1 CAR-T cells	* Cyclic administration of ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following lymphodepletion regimen 1. * Rimiducid may be administered as indicated.
P-MUC1C-ALLO1 CAR-T cells (Multiple Dose - Arm B)	Rimiducid	* Cyclic administration of ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following lymphodepletion regimen 1. * Rimiducid may be administered as indicated.
P-MUC1C-ALLO1 CAR-T cells (Single Dose - Arm C)	P-MUC1C-ALLO1 CAR-T cells	* Single ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following lymphodepletion regimen 2. * Rimiducid may be administered as indicated.
P-MUC1C-ALLO1 CAR-T cells (Single Dose - Arm C)	Rimiducid	* Single ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following lymphodepletion regimen 2. * Rimiducid may be administered as indicated.
P-MUC1C-ALLO1 CAR-T cells (Multiple Dose - Arm D)	P-MUC1C-ALLO1 CAR-T cells	* Cyclic administration of ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following lymphodepletion regimen 2. * Rimiducid may be administered as indicated.
P-MUC1C-ALLO1 CAR-T cells (Multiple Dose - Arm D)	Rimiducid	* Cyclic administration of ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following lymphodepletion regimen 2. * Rimiducid may be administered as indicated.
P-MUC1C-ALLO1 CAR-T cells (Single Dose - Arm A1)	P-MUC1C-ALLO1 CAR-T cells	* Single ascending A1 dose cohorts, given in a single intravenous infusion of CAR-T cells, following lymphodepletion regimen 1. * Rimiducid may be administered as indicated.
P-MUC1C-ALLO1 CAR-T cells (Multiple Dose - Arm F)	P-MUC1C-ALLO1 CAR-T cells	* Cyclic administration of ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following assigned lymphodepletion regimen. * Rimiducid may be administered as indicated.
P-MUC1C-ALLO1 CAR-T cells (Multiple Dose - Arm F)	Rimiducid	* Cyclic administration of ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following assigned lymphodepletion regimen. * Rimiducid may be administered as indicated.
P-MUC1C-ALLO1 CAR-T cells (Single Dose - Arm M)	P-MUC1C-ALLO1 CAR-T cells	* Single ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following assigned lymphodepletion regimen. * Rimiducid may be administered as indicated.
P-MUC1C-ALLO1 CAR-T cells (Single Dose - Arm M)	Rimiducid	* Single ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following assigned lymphodepletion regimen. * Rimiducid may be administered as indicated.
P-MUC1C-ALLO1 CAR-T cells (Single Dose - Arm E)	Rimiducid	* Single ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following assigned lymphodepletion regimen. * Rimiducid may be administered as indicated.

Primary Outcome Measures

Name	Time	Method
Determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of P-MUC1C-ALLO1	Baseline through Day 28	Number of subjects with a dose limiting toxicity (DLT)
Evaluate the overall safety and tolerability profile of P-MUC1C-ALLO1	Baseline through 15 years	Frequency and severity of adverse events
Evaluate the preliminary efficacy of P-MUC1C-ALLO1	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): Overall Response Rate (ORR)

Trial Locations

Locations (15)

University of California, Irvine Medical Center; 🇺🇸 Irvine, California, United States

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

Cedars Sinai Medical Center; 🇺🇸 Los Angeles, California, United States

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

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

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

University of Iowa Hospitals and Clinics; 🇺🇸 Iowa City, Iowa, United States

University of Kansas Cancer Center; 🇺🇸 Westwood, Kansas, United States

Cancer Center of Kansas; 🇺🇸 Wichita, Kansas, United States

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

University of Nebraska Medical Center; 🇺🇸 Omaha, Nebraska, United States

Montefiore Medical Center; 🇺🇸 Bronx, New York, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

NEXT Oncology; 🇺🇸 San Antonio, Texas, United States

Froedtert Hospital and the Medical College of Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States