p-muc1c-allo1 allogeneic car-t cells in the treatment of subjects with advanced or metastatic solid tumors

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

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.

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 criteria:
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