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

• ClinicalTrials.gov Identifier: NCT03970382
• Recruitment Status: Suspended
• First Posted: May 31, 2019
• Last Update Posted: August 18, 2022
• Sponsor: PACT Pharma, Inc.
• Information provided by (Responsible Party): PACT Pharma, Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Solid Tumor	Biological: NeoTCR-P1 adoptive cell therapy; Biological: nivolumab; Biological: IL-2	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 21 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: July 3, 2019
• Estimated Primary Completion Date: August 12, 2022
• Estimated Study Completion Date: August 12, 2022

Arms and Interventions

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 Name: 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; aldesleukin; interleukin-2

Outcome Measures

Primary Outcome Measures :

1. Incidence of adverse events as defined as DLTs [ Time Frame: 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.
2. Number of participants with adverse events as a measure of safety and tolerability of NeoTCR-P1 or NeoTCR-P1 in combination with nivolumab [ Time Frame: 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.
3. Maximum Tolerated Dose (MTD) of NeoTCR-P1 [ Time Frame: 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.
4. Feasibility of manufacturing NeoTCR-P1 [ Time Frame: 2 years ]
   Percent of screened patients that enroll on study and receive NeoTCR-P1

Secondary Outcome Measures :

1. Maximum concentration of NeoTCR-P1 (Cmax) in the peripheral blood [ Time Frame: 2 years ]
2. Area-under-the-concentration-vs-time-curve (AUC) in the peripheral blood [ Time Frame: 28 days ]
3. Persistence of NeoTCR-P1 in samples of peripheral blood [ Time Frame: 2 years ]
4. 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 ]
   ORR will be defined as Complete Response (CR) or Partial Response (PR) per RECIST v1.1, as determined by the investigator
5. 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 ]
   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
6. 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 ]
   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
7. 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 ]
   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.

Eligibility Criteria

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

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.

Contacts and Locations

Locations

United States, California

City of Hope

Duarte, California, United States, 91010

University of California, Los Angeles

Los Angeles, California, United States, 90024

University of California, Irvine Medical Center

Orange, California, United States, 92868

University of California, Davis

Sacramento, California, United States, 95817

University of California, San Francisco

San Francisco, California, United States, 94158

United States, Illinois

Northwestern University Medical Center

Chicago, Illinois, United States, 60611

United States, New York

Memorial Sloan Kettering Cancer Center

New York, New York, United States, 10065

United States, Tennessee

Tennessee Oncology

Nashville, Tennessee, United States, 37203

United States, Washington

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States, 98109

Sponsors and Collaborators

PACT Pharma, Inc.

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: PACT Pharma, Inc.
• ClinicalTrials.gov Identifier: NCT03970382
• Other Study ID Numbers: PACT-0101
• First Posted: May 31, 2019
• Last Update Posted: August 18, 2022
• Last Verified: August 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by PACT Pharma, Inc.:

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

Additional relevant MeSH terms:

Neoplasms; Aldesleukin; Nivolumab; Interleukin-2; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immune Checkpoint Inhibitors; Molecular Mechanisms of Pharmacological Action; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-HIV Agents; Anti-Retroviral Agents; Antiviral Agents; Anti-Infective Agents