Clinical Trials /

A Study of Gene Edited Autologous Neoantigen Targeted TCR T Cells With or Without Anti-PD-1 in Patients With Solid Tumors

NCT03970382

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.

Related Conditions:
  • Breast Carcinoma
  • Colorectal Carcinoma
  • Melanoma
  • Ovarian Carcinoma
  • Prostate Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

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

  • Solid Tumor

Interventions

DrugSynonymsArms
NeoTCR-P1 adoptive cell therapyNeoTCR-P1
nivolumabOpdivoNeoTCR-P1 plus nivolumab

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

NameTypeDescriptionInterventions
NeoTCR-P1ExperimentalSingle dose of NeoTCR-P1
  • NeoTCR-P1 adoptive cell therapy
NeoTCR-P1 plus nivolumabExperimentalSingle dose of NeoTCR-P1 plus nivolumab 480mg IV every four weeks for up to 6 doses.
  • NeoTCR-P1 adoptive cell therapy
  • nivolumab

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 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

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