P-MUC1C-ALLO1 Allogeneic CAR-T Cells in the Treatment of Subjects With Advanced or Metastatic Solid Tumors
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: P-MUC1C-ALLO1 CAR-T cells (Single Dose - Arm A) 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
P-MUC1C-ALLO1 is an allogeneic CAR-T cell therapy designed to target cancer cells expressing MUC1-C.
Drug: Rimiducid
Rimiducid (safety switch activator) may be administered as indicated.
|
| Experimental: P-MUC1C-ALLO1 CAR-T cells (Multiple Dose - Arm B) 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
P-MUC1C-ALLO1 is an allogeneic CAR-T cell therapy designed to target cancer cells expressing MUC1-C.
Drug: Rimiducid
Rimiducid (safety switch activator) may be administered as indicated.
|
| Experimental: P-MUC1C-ALLO1 CAR-T cells (Single Dose - Arm C) 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
P-MUC1C-ALLO1 is an allogeneic CAR-T cell therapy designed to target cancer cells expressing MUC1-C.
Drug: Rimiducid
Rimiducid (safety switch activator) may be administered as indicated.
|
| Experimental: P-MUC1C-ALLO1 CAR-T cells (Multiple Dose - Arm D) 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
P-MUC1C-ALLO1 is an allogeneic CAR-T cell therapy designed to target cancer cells expressing MUC1-C.
Drug: Rimiducid
Rimiducid (safety switch activator) may be administered as indicated.
|
Outcome Measures
Primary Outcome Measures
- 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)
Eligibility Criteria
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, refractory to standard of care therapy or ineligible or refused other existing treatment options
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Must have progressed during or after last therapy and have measurable disease
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Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 or Karnofsky performance status ≥70%
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Must have adequate vital organ function within pre-determined parameters
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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:
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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
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Has a history of or active autoimmune disease
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Has a history of significant central nervous system (CNS) disease, such as stroke, epilepsy
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Has an active systemic (viral, bacterial, or fungal) infection
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of California, San Francisco | San Francisco | California | United States | 94143 |
| 2 | Sarah Cannon Research Institute at HealthONE | Denver | Colorado | United States | 80218 |
| 3 | NEXT Oncology | San Antonio | Texas | United States | 78229 |
Sponsors and Collaborators
- Poseida Therapeutics, Inc.
Investigators
- Study Director: Rajesh Belani, M.D., Sponsor Executive Medical Director
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- P-MUC1C-ALLO1-001