Solid Tumor
Conditions
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
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.
Interventions
BIOLOGICALNeoTCR-P1 adoptive cell therapy
The investigational agent in this protocol is NeoTCR P1, an autologous adoptive T cell therapy (ACT) for patients with solid cancer. NeoTCR P1 is composed of apheresis derived CD8 and CD4 T cells that are precision genome engineered to express one autologous TCR of native sequence that targets a neoepitope (neoE) presented by human leukocyte antigen (HLA) receptors exclusively on the surface of that patient's tumor cells and not on other cells in the body.
BIOLOGICALnivolumab
Nivolumab is a human IgG4 anti-PD-1 monoclonal antibody
BIOLOGICALIL-2
IL-2 is a biologic response modifier. It is a type of protein called a cytokine.
Sponsors
PACT Pharma, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Maximum concentration of NeoTCR-P1 (Cmax) in the peripheral blood | 2 years | — |
| 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. |
| 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 |
| 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 |
Countries
United States
Outcome results
None listed