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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase 1 Dose Escalation and Expanded Cohort Study of P-MUC1C-ALLO1 in Adult Subjects With Advanced or Metastatic Solid Tumors

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

Intervention / Treatment
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* Biological: P-MUC1C-ALLO1 CAR-T cells
* Drug: Rimiducid


Participation Criteria
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Eligibility Criteria
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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, refractory to standard of care therapy or ineligible or refused other existing treatment options Must have progressed during or after last therapy 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 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 conditioning chemotherapy 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Open label, 3 + 3 design of dose-escalating cohorts with open label, dose expansion at recommended phase 2 dose (RP2D)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: P-MUC1C-ALLO1 CAR-T cells (Single Dose - Arm A)<br>Single ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following conditioning chemotherapy regimen 1. Rimiducid may be administered as indicated. | Biological: P-MUC1C-ALLO1 CAR-T cells<br>* P-MUC1C-ALLO1 is an allogeneic CAR-T cell therapy designed to target cancer cells expressing MUC1-C.<br>Drug: Rimiducid<br>* Rimiducid (safety switch activator) may be administered as indicated.<br>|
| Experimental: P-MUC1C-ALLO1 CAR-T cells (Multiple Dose - Arm B)<br>Cyclic administration of ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following conditioning chemotherapy regimen 1. Rimiducid may be administered as indicated. | Biological: P-MUC1C-ALLO1 CAR-T cells<br>* P-MUC1C-ALLO1 is an allogeneic CAR-T cell therapy designed to target cancer cells expressing MUC1-C.<br>Drug: Rimiducid<br>* Rimiducid (safety switch activator) may be administered as indicated.<br>|
| Experimental: P-MUC1C-ALLO1 CAR-T cells (Single Dose - Arm C)<br>Single ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following conditioning chemotherapy regimen 2. Rimiducid may be administered as indicated. | Biological: P-MUC1C-ALLO1 CAR-T cells<br>* P-MUC1C-ALLO1 is an allogeneic CAR-T cell therapy designed to target cancer cells expressing MUC1-C.<br>Drug: Rimiducid<br>* Rimiducid (safety switch activator) may be administered as indicated.<br>|
| Experimental: P-MUC1C-ALLO1 CAR-T cells (Multiple Dose - Arm D)<br>Cyclic administration of ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following conditioning chemotherapy regimen 2. Rimiducid may be administered as indicated. | Biological: P-MUC1C-ALLO1 CAR-T cells<br>* P-MUC1C-ALLO1 is an allogeneic CAR-T cell therapy designed to target cancer cells expressing MUC1-C.<br>Drug: Rimiducid<br>* Rimiducid (safety switch activator) may be administered as indicated.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of P-MUC1C-ALLO1 | Number of subjects with a dose limiting toxicity (DLT) | Baseline through Day 28 | 
| Evaluate the overall safety and tolerability profile of P-MUC1C-ALLO1 | Frequency and severity of adverse events | Baseline through 15 years | 
| Evaluate the preliminary efficacy of P-MUC1C-ALLO1 | 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) | Baseline through 15 years |