Overview
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.
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.
Eligibility
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