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

Purpose

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.

Conditions

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

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 1
Study Type
Interventional
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 recommended phase 2 dose (RP2D)
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
P-MUC1C-ALLO1 CAR-T cells (Single Dose - Arm A) 		- Single ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following lymphodepletion regimen 1. - Rimiducid may be administered as indicated.
  • Biological: P-MUC1C-ALLO1 CAR-T cells
    P-MUC1C-ALLO1 is an allogeneic CAR-T cell therapy designed to target cancer cells expressing MUC1-C.
  • Drug: Rimiducid
    Rimiducid (safety switch activator) may be administered as indicated.
Experimental
P-MUC1C-ALLO1 CAR-T cells (Multiple Dose - Arm B) 		- 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.
  • Biological: P-MUC1C-ALLO1 CAR-T cells
    P-MUC1C-ALLO1 is an allogeneic CAR-T cell therapy designed to target cancer cells expressing MUC1-C.
  • Drug: Rimiducid
    Rimiducid (safety switch activator) may be administered as indicated.
Experimental
P-MUC1C-ALLO1 CAR-T cells (Single Dose - Arm C) 		- Single ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following lymphodepletion regimen 2. - Rimiducid may be administered as indicated.
  • Biological: P-MUC1C-ALLO1 CAR-T cells
    P-MUC1C-ALLO1 is an allogeneic CAR-T cell therapy designed to target cancer cells expressing MUC1-C.
  • Drug: Rimiducid
    Rimiducid (safety switch activator) may be administered as indicated.
Experimental
P-MUC1C-ALLO1 CAR-T cells (Multiple Dose - Arm D) 		- 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.
  • Biological: P-MUC1C-ALLO1 CAR-T cells
    P-MUC1C-ALLO1 is an allogeneic CAR-T cell therapy designed to target cancer cells expressing MUC1-C.
  • Drug: Rimiducid
    Rimiducid (safety switch activator) may be administered as indicated.
Experimental
P-MUC1C-ALLO1 CAR-T cells (Single Dose - Arm A1) 		- 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.
  • Biological: P-MUC1C-ALLO1 CAR-T cells
    P-MUC1C-ALLO1 is an allogeneic CAR-T cell therapy designed to target cancer cells expressing MUC1-C.
  • Drug: Rimiducid
    Rimiducid (safety switch activator) may be administered as indicated.
Experimental
P-MUC1C-ALLO1 CAR-T cells (Single Dose - Arm E) 		- Single ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following assigned lymphodepletion regimen. - Rimiducid may be administered as indicated.
  • Biological: P-MUC1C-ALLO1 CAR-T cells
    P-MUC1C-ALLO1 is an allogeneic CAR-T cell therapy designed to target cancer cells expressing MUC1-C.
  • Drug: Rimiducid
    Rimiducid (safety switch activator) may be administered as indicated.
Experimental
P-MUC1C-ALLO1 CAR-T cells (Multiple Dose - Arm F) 		- 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.
  • Biological: P-MUC1C-ALLO1 CAR-T cells
    P-MUC1C-ALLO1 is an allogeneic CAR-T cell therapy designed to target cancer cells expressing MUC1-C.
  • Drug: Rimiducid
    Rimiducid (safety switch activator) may be administered as indicated.
Experimental
P-MUC1C-ALLO1 CAR-T cells (Single Dose - Arm M) 		- Single ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following assigned lymphodepletion regimen. - Rimiducid may be administered as indicated.
  • Biological: P-MUC1C-ALLO1 CAR-T cells
    P-MUC1C-ALLO1 is an allogeneic CAR-T cell therapy designed to target cancer cells expressing MUC1-C.
  • Drug: Rimiducid
    Rimiducid (safety switch activator) may be administered as indicated.

More Details

Status
Active, not recruiting
Sponsor
Poseida Therapeutics, Inc.

Study Contact

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.