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

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

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.

Study Overview

• Status: Suspended
• Conditions: Solid Tumor
• Intervention / Treatment: Biological: NeoTCR-P1 adoptive cell therapy; Biological: nivolumab; Biological: IL-2

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope
    • Los Angeles, California, United States, 90024
      • University of California, Los Angeles
    • Orange, California, United States, 92868
      • University of California, Irvine Medical Center
    • Sacramento, California, United States, 95817
      • University of California, Davis
    • San Francisco, California, United States, 94158
      • University of California, San Francisco
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University Medical Center
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NeoTCR-P1; Single dose of NeoTCR-P1	Biological: NeoTCR-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.
Experimental: NeoTCR-P1 plus nivolumab; Single dose of NeoTCR-P1 plus nivolumab 480mg IV every four weeks for up to 6 doses.	Biological: NeoTCR-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.; Biological: nivolumab; Nivolumab is a human IgG4 anti-PD-1 monoclonal antibody; Other Names: Opdivo
Experimental: NeoTCR-P1 plus IL-2; Single dose of NeoTCR-P1 plus IL-2 500,000 IU/m2 SC twice daily (BID) for 7 days.	Biological: NeoTCR-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.; Biological: IL-2; IL-2 is a biologic response modifier. It is a type of protein called a cytokine.; Other Names: Proleukin; interleukin-2; aldesleukin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events as defined as DLTs	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.	28 days
Number of participants with adverse events as a measure of safety and tolerability of NeoTCR-P1 or NeoTCR-P1 in combination with nivolumab	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.	2 years
Maximum Tolerated Dose (MTD) of NeoTCR-P1	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.	2 years
Feasibility of manufacturing NeoTCR-P1	Percent of screened patients that enroll on study and receive NeoTCR-P1	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	ORR will be defined as Complete Response (CR) or Partial Response (PR) per RECIST v1.1, as determined by the investigator	2 years
Duration of Response mediated by neoTCR-P1 administered as a single agent or in combination with nivolumab to participants with solid tumors	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	2 years
Progression free survival (PFS) in participants with solid tumors following infusion of NeoTCR-P1 as a single agent or in combination with nivolumab	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	2 years
Overall survival (OS) in participants with solid tumors following infusion of NeoTCR-P1 as a single agent or in combination with nivolumab	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.	2 years

Collaborators and Investigators

• Sponsor: PACT Pharma, Inc.

Publications and helpful links

General Publications

• Levy PL, Gros A. Fast track to personalized TCR T cell therapies. Cancer Cell. 2022 May 9;40(5):447-449. doi: 10.1016/j.ccell.2022.04.013. Epub 2022 May 9.

Study record dates

Study Major Dates

• Study Start (Actual): July 3, 2019
• Primary Completion (Anticipated): August 12, 2022
• Study Completion (Anticipated): August 12, 2022

Study Registration Dates

• First Submitted: May 6, 2019
• First Submitted That Met QC Criteria: May 30, 2019
• First Posted (Actual): May 31, 2019

Study Record Updates

• Last Update Posted (Actual): August 18, 2022
• Last Update Submitted That Met QC Criteria: August 16, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: colorectal cancer; immunotherapy; prostate cancer; non-small cell lung cancer; gene therapy; cell therapy; ovarian cancer; PD-1; melanoma; IL-2; urothelial carcinoma; T lymphocyte; HR+ breast cancer; triple negative breast cancer; HER2 negative breast cancer; neoantigen; adoptive cell therapy; T cell receptor; TCR-engineered T cells; personalized cell therapy; head and neck squamous carcinoma
• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Aldesleukin; Nivolumab; Interleukin-2
• Other Study ID Numbers: PACT-0101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No