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

Poseida Therapeutics

Status and phase: Active, not recruiting; Phase 1

Conditions: Breast Cancer; Nasopharyngeal Cancer; Gastric Cancer; Non Small Cell Lung Cancer; Renal Cell Carcinoma; Ovarian Cancer; Head and Neck Squamous Cell Carcinoma; Pancreatic Cancer; Colorectal Cancer

Treatments: Biological: P-MUC1C-ALLO1 CAR-T cells; Drug: Rimiducid

Study type: Interventional

Funder types: Industry

Identifiers

NCT05239143

P-MUC1C-ALLO1-001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 180 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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
• Must have progressed during or after last therapy, developed intolerance/toxicity to current treatment, or ineligible or refused other existing treatment options, 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

Exclusion criteria

• Has inadequate venous access
• Has an active second malignancy (not disease free for at least 5 years) 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 lymphodepletion
• 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
• Has received anti-cancer monoclonal antibody therapy within 4 weeks of initiating LD therapy

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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180 participants in 8 patient groups

P-MUC1C-ALLO1 CAR-T cells (Single Dose - Arm A)

Experimental group

Description:

* Single ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following lymphodepletion regimen 1. * Rimiducid may be administered as indicated.

Treatment:

Drug: Rimiducid

Biological: P-MUC1C-ALLO1 CAR-T cells

P-MUC1C-ALLO1 CAR-T cells (Multiple Dose - Arm B)

Experimental group

Description:

* 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.

Treatment:

Drug: Rimiducid

Biological: P-MUC1C-ALLO1 CAR-T cells

P-MUC1C-ALLO1 CAR-T cells (Single Dose - Arm C)

Experimental group

Description:

* Single ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following lymphodepletion regimen 2. * Rimiducid may be administered as indicated.

Treatment:

Drug: Rimiducid

Biological: P-MUC1C-ALLO1 CAR-T cells

P-MUC1C-ALLO1 CAR-T cells (Multiple Dose - Arm D)

Experimental group

Description:

* 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.

Treatment:

Drug: Rimiducid

Biological: P-MUC1C-ALLO1 CAR-T cells

P-MUC1C-ALLO1 CAR-T cells (Single Dose - Arm A1)

Experimental group

Description:

* 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.

Treatment:

Drug: Rimiducid

Biological: P-MUC1C-ALLO1 CAR-T cells

P-MUC1C-ALLO1 CAR-T cells (Single Dose - Arm E)

Experimental group

Description:

* Single ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following assigned lymphodepletion regimen. * Rimiducid may be administered as indicated.

Treatment:

Drug: Rimiducid

Biological: P-MUC1C-ALLO1 CAR-T cells

P-MUC1C-ALLO1 CAR-T cells (Multiple Dose - Arm F)

Experimental group

Description:

* 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.

Treatment:

Drug: Rimiducid

Biological: P-MUC1C-ALLO1 CAR-T cells

P-MUC1C-ALLO1 CAR-T cells (Single Dose - Arm M)

Experimental group

Description:

* Single ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following assigned lymphodepletion regimen. * Rimiducid may be administered as indicated.

Treatment:

Drug: Rimiducid

Biological: P-MUC1C-ALLO1 CAR-T cells