A Study of Gene Edited Autologous Neoantigen Targeted TCR T Cells With or Without Anti-PD-1 in Patients With Solid Tumors
- Conditions
- Solid Tumor
- Interventions
- Biological: NeoTCR-P1 adoptive cell therapyBiological: IL-2Biological: nivolumab
- Registration Number
- NCT03970382
- Lead Sponsor
- PACT Pharma, Inc.
- Brief Summary
This is a first in human, single arm, open label, Phase 1a/1b study to determine the safety, feasibility, and efficacy of a single dose of NeoTCR-P1 T cells in participants with solid tumors.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- SUSPENDED
- Sex
- All
- Target Recruitment
- 21
- Histologically or cytologically documented incurable or metastatic solid tumors of the following types: melanoma, UC, ovarian cancer, colorectal cancer, breast cancer (HR+), or prostate cancer.
- Disease has progressed after at least one available standard therapy or no additional curative therapies are available.
- Measurable disease per RECIST v1.1
- Eastern cooperative oncology group (ECOG) performance status of 0 or 1
- Adequate hematologic and end organ function determined within 30 days prior to enrollment.
- Disease-specific criteria related to the specific tumor type are required.
Note: There are additional inclusion criteria. The study center will determine if you meet all of the criteria.
- Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, and/or inherited liver disease
- Known primary central nervous system (CNS) malignancy or symptomatic CNS metastases
- Uncontrolled or symptomatic hypercalcemia
- Pregnancy, lactation, or breastfeeding
- Prior allogeneic stem cell transplant or solid organ transplant
- Prior chimeric antigen receptor therapy or other genetically modified T cell therapy
- Active HIV, Hepatitis B, or Hepatitis C infection
- Active tuberculosis
- Severe infection within 2 weeks prior to enrollment
- Major surgical procedure within 4 weeks prior to enrollment or anticipation of need for a major surgical procedure during the study.
Note: There are additional exclusion criteria. The study center will determine if you meet all of the criteria.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description NeoTCR-P1 plus IL-2 NeoTCR-P1 adoptive cell therapy Single dose of NeoTCR-P1 plus IL-2 500,000 IU/m2 SC twice daily (BID) for 7 days. NeoTCR-P1 NeoTCR-P1 adoptive cell therapy Single dose of NeoTCR-P1 NeoTCR-P1 plus IL-2 IL-2 Single dose of NeoTCR-P1 plus IL-2 500,000 IU/m2 SC twice daily (BID) for 7 days. NeoTCR-P1 plus nivolumab NeoTCR-P1 adoptive cell therapy Single dose of NeoTCR-P1 plus nivolumab 480mg IV every four weeks for up to 6 doses. NeoTCR-P1 plus nivolumab nivolumab Single dose of NeoTCR-P1 plus nivolumab 480mg IV every four weeks for up to 6 doses.
- Primary Outcome Measures
Name Time Method Incidence of adverse events as defined as DLTs 28 days Dose limiting toxicity (DLT) is defined as protocol-defined adverse events that occur within 28 days following infusion of Neo-TCR-P1 administered as a single agent without or with IL-2, or in combination with nivolumab.
Number of participants with adverse events as a measure of safety and tolerability of NeoTCR-P1 or NeoTCR-P1 in combination with nivolumab 2 years Toxicity will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, version 5.0). Cytokine release syndrome (CRS) and neurotoxicity associated with NeoTCR-P1 will be graded according to ASBMT consensus grading.
Maximum Tolerated Dose (MTD) of NeoTCR-P1 2 years The MTD is defined as the highest dose with an observed incidence of DLT in no more than one out of six patients treated at a particular dose level.
Feasibility of manufacturing NeoTCR-P1 2 years Percent of screened patients that enroll on study and receive NeoTCR-P1
- Secondary Outcome Measures
Name Time Method Maximum concentration of NeoTCR-P1 (Cmax) in the peripheral blood 2 years Area-under-the-concentration-vs-time-curve (AUC) in the peripheral blood 28 days Persistence of NeoTCR-P1 in samples of peripheral blood 2 years Objective Response Rate (ORR) in participants with solid tumors following infusion of NeoTCR-P1 as a single agent or in combination with nivolumab 2 years ORR will be defined as Complete Response (CR) or Partial Response (PR) per RECIST v1.1, as determined by the investigator
Duration of Response mediated by neoTCR-P1 administered as a single agent or in combination with nivolumab to participants with solid tumors 2 years Duration of response, defined as time from the first occurrence of a documented objective response to the time of relapse or death from any cause
Progression free survival (PFS) in participants with solid tumors following infusion of NeoTCR-P1 as a single agent or in combination with nivolumab 2 years PFS is defined from date of administration of NeoTCR-P1 cell infusion to the date of disease progression per the RECIST v1.1 or death as a result of any cause. Subjects who do not meet criteria for progression by the analysis data cut-off date will be censored at their last evaluable disease assessment date
Overall survival (OS) in participants with solid tumors following infusion of NeoTCR-P1 as a single agent or in combination with nivolumab 2 years OS will be measured from the date of administration of NeoTCR-P1 to the date of death. Subjects who have not died by the analysis data cut-off date will be censored at their last date of contact.
Trial Locations
- Locations (9)
Tennessee Oncology
🇺🇸Nashville, Tennessee, United States
University of California, Los Angeles
🇺🇸Los Angeles, California, United States
University of California, Davis
🇺🇸Sacramento, California, United States
University of California, San Francisco
🇺🇸San Francisco, California, United States
City of Hope
🇺🇸Duarte, California, United States
University of California, Irvine Medical Center
🇺🇸Orange, California, United States
Fred Hutchinson Cancer Research Center
🇺🇸Seattle, Washington, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Northwestern University Medical Center
🇺🇸Chicago, Illinois, United States