Breast Cancer, Colorectal Cancer, Gastric Cancer, Head and Neck Squamous Cell Carcinoma, Nasopharyngeal Cancer, Non Small Cell Lung Cancer, Ovarian Cancer, Pancreatic Cancer, Renal Cell Carcinoma
Conditions
Brief 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.
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.
Interventions
DRUGRimiducid
Rimiducid (safety switch activator) may be administered as indicated.
BIOLOGICALP-MUC1C-ALLO1 CAR-T cells
P-MUC1C-ALLO1 is an allogeneic CAR-T cell therapy designed to target cancer cells expressing MUC1-C.
Sponsors
Poseida Therapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open label, 3 + 3 design of dose-escalating cohorts with open label, dose expansion at recommended phase 2 dose (RP2D)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of P-MUC1C-ALLO1 | Baseline through Day 28 | Number of subjects with a dose limiting toxicity (DLT) |
| Evaluate the overall safety and tolerability profile of P-MUC1C-ALLO1 | Baseline through 15 years | Frequency and severity of adverse events |
| Evaluate the preliminary efficacy of P-MUC1C-ALLO1 | Baseline through 15 years | According to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, secondarily Immune Response Evaluation Criteria in Solid Tumors (iRECIST): Overall Response Rate (ORR) |
Countries
United States
Contacts
STUDY_DIRECTORSimon Heidegger, M.D.
Lead Medical Director, Oncology, Genentech Research Early Development
Outcome results
None listed