Description:
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.
Title
- Brief Title: A Study of Gene Edited Autologous Neoantigen Targeted TCR T Cells With or Without Anti-PD-1 in Patients With Solid Tumors
- Official Title: A Phase 1a/1b, Open-label First-in-human Study of the Safety, Tolerability and Feasibility of Gene-edited Autologous NeoTCR-T Cells (NeoTCR-P1) Administered as a Single Agent or in Combination With Anti-PD-1 to Patients With Locally Advanced or Metastatic Solid Tumors
Clinical Trial IDs
- ORG STUDY ID:
PACT-0101
- NCT ID:
NCT03970382
Conditions
Interventions
Drug | Synonyms | Arms |
---|
NeoTCR-P1 adoptive cell therapy | | NeoTCR-P1 |
nivolumab | Opdivo | NeoTCR-P1 plus nivolumab |
IL-2 | Proleukin, aldesleukin, interleukin-2 | NeoTCR-P1 plus IL-2 |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
NeoTCR-P1 | Experimental | Single dose of NeoTCR-P1 | - NeoTCR-P1 adoptive cell therapy
|
NeoTCR-P1 plus nivolumab | Experimental | Single dose of NeoTCR-P1 plus nivolumab 480mg IV every four weeks for up to 6 doses. | - NeoTCR-P1 adoptive cell therapy
- nivolumab
|
NeoTCR-P1 plus IL-2 | Experimental | Single dose of NeoTCR-P1 plus IL-2 500,000 IU/m2 SC twice daily (BID) for 7 days. | - NeoTCR-P1 adoptive cell therapy
- IL-2
|
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion 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.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Incidence of adverse events as defined as DLTs |
Time Frame: | 28 days |
Safety Issue: | |
Description: | 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. |
Secondary Outcome Measures
Measure: | Maximum concentration of NeoTCR-P1 (Cmax) in the peripheral blood |
Time Frame: | 2 years |
Safety Issue: | |
Description: | |
Measure: | Area-under-the-concentration-vs-time-curve (AUC) in the peripheral blood |
Time Frame: | 28 days |
Safety Issue: | |
Description: | |
Measure: | Persistence of NeoTCR-P1 in samples of peripheral blood |
Time Frame: | 2 years |
Safety Issue: | |
Description: | |
Measure: | Objective Response Rate (ORR) in participants with solid tumors following infusion of NeoTCR-P1 as a single agent or in combination with nivolumab |
Time Frame: | 2 years |
Safety Issue: | |
Description: | ORR will be defined as Complete Response (CR) or Partial Response (PR) per RECIST v1.1, as determined by the investigator |
Measure: | Duration of Response mediated by neoTCR-P1 administered as a single agent or in combination with nivolumab to participants with solid tumors |
Time Frame: | 2 years |
Safety Issue: | |
Description: | 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 |
Measure: | Progression free survival (PFS) in participants with solid tumors following infusion of NeoTCR-P1 as a single agent or in combination with nivolumab |
Time Frame: | 2 years |
Safety Issue: | |
Description: | 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 |
Measure: | Overall survival (OS) in participants with solid tumors following infusion of NeoTCR-P1 as a single agent or in combination with nivolumab |
Time Frame: | 2 years |
Safety Issue: | |
Description: | 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. |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | PACT Pharma, Inc. |
Trial Keywords
- melanoma
- HR+ breast cancer
- ovarian cancer
- prostate cancer
- colorectal cancer
- urothelial carcinoma
- adoptive cell therapy
- neoantigen
- T cell receptor
- T lymphocyte
- TCR-engineered T cells
- personalized cell therapy
- cell therapy
- immunotherapy
- gene therapy
- PD-1
- non-small cell lung cancer
- head and neck squamous carcinoma
- HER2 negative breast cancer
- triple negative breast cancer
- IL-2
Last Updated
August 18, 2021