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

Brief summary public domain (ClinicalTrials.gov)

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 public domain (ClinicalTrials.gov)

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.

Intervention public domain (ClinicalTrials.gov)

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.

Intervention public domain (ClinicalTrials.gov)

Drug: Rimiducid. Rimiducid (safety switch activator) may be administered as indicated.

Arm public domain (ClinicalTrials.gov)

P-MUC1C-ALLO1 CAR-T cells (Single Dose - Arm A) (experimental): * Single ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following lymphodepletion regimen 1. * Rimiducid may be administered as indicated.

Arm public domain (ClinicalTrials.gov)

P-MUC1C-ALLO1 CAR-T cells (Multiple Dose - Arm B) (experimental): * 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.

Arm public domain (ClinicalTrials.gov)

P-MUC1C-ALLO1 CAR-T cells (Single Dose - Arm C) (experimental): * Single ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following lymphodepletion regimen 2. * Rimiducid may be administered as indicated.

Arm public domain (ClinicalTrials.gov)

P-MUC1C-ALLO1 CAR-T cells (Multiple Dose - Arm D) (experimental): * 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.

Arm public domain (ClinicalTrials.gov)

P-MUC1C-ALLO1 CAR-T cells (Single Dose - Arm A1) (experimental): * 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.

Arm public domain (ClinicalTrials.gov)

P-MUC1C-ALLO1 CAR-T cells (Single Dose - Arm E) (experimental): * Single ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following assigned lymphodepletion regimen. * Rimiducid may be administered as indicated.

Arm public domain (ClinicalTrials.gov)

P-MUC1C-ALLO1 CAR-T cells (Multiple Dose - Arm F) (experimental): * 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.

Arm public domain (ClinicalTrials.gov)

P-MUC1C-ALLO1 CAR-T cells (Single Dose - Arm M) (experimental): * Single ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following assigned lymphodepletion regimen. * Rimiducid may be administered as indicated.

Eligibility public domain (ClinicalTrials.gov)

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