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

NCT ID: NCT03970382

Last Updated: 2022-08-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

SUSPENDED

Clinical Phase

PHASE1

Total Enrollment

21 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-07-03

Study Completion Date

2022-08-12

Brief Summary

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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.

Detailed Description

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Conditions

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Solid Tumor

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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NeoTCR-P1

Single dose of NeoTCR-P1

Group Type EXPERIMENTAL

NeoTCR-P1 adoptive cell therapy

Intervention Type BIOLOGICAL

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.

NeoTCR-P1 plus nivolumab

Single dose of NeoTCR-P1 plus nivolumab 480mg IV every four weeks for up to 6 doses.

Group Type EXPERIMENTAL

NeoTCR-P1 adoptive cell therapy

Intervention Type BIOLOGICAL

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.

nivolumab

Intervention Type BIOLOGICAL

Nivolumab is a human IgG4 anti-PD-1 monoclonal antibody

NeoTCR-P1 plus IL-2

Single dose of NeoTCR-P1 plus IL-2 500,000 IU/m2 SC twice daily (BID) for 7 days.

Group Type EXPERIMENTAL

NeoTCR-P1 adoptive cell therapy

Intervention Type BIOLOGICAL

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.

IL-2

Intervention Type BIOLOGICAL

IL-2 is a biologic response modifier. It is a type of protein called a cytokine.

Interventions

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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.

Intervention Type BIOLOGICAL

nivolumab

Nivolumab is a human IgG4 anti-PD-1 monoclonal antibody

Intervention Type BIOLOGICAL

IL-2

IL-2 is a biologic response modifier. It is a type of protein called a cytokine.

Intervention Type BIOLOGICAL

Other Intervention Names

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Opdivo Proleukin aldesleukin interleukin-2

Eligibility Criteria

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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.

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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PACT Pharma, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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City of Hope

Duarte, California, United States

Site Status

University of California, Los Angeles

Los Angeles, California, United States

Site Status

University of California, Irvine Medical Center

Orange, California, United States

Site Status

University of California, Davis

Sacramento, California, United States

Site Status

University of California, San Francisco

San Francisco, California, United States

Site Status

Northwestern University Medical Center

Chicago, Illinois, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Tennessee Oncology

Nashville, Tennessee, United States

Site Status

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Site Status

Countries

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United States

References

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Foy SP, Jacoby K, Bota DA, Hunter T, Pan Z, Stawiski E, Ma Y, Lu W, Peng S, Wang CL, Yuen B, Dalmas O, Heeringa K, Sennino B, Conroy A, Bethune MT, Mende I, White W, Kukreja M, Gunturu S, Humphrey E, Hussaini A, An D, Litterman AJ, Quach BB, Ng AHC, Lu Y, Smith C, Campbell KM, Anaya D, Skrdlant L, Huang EY, Mendoza V, Mathur J, Dengler L, Purandare B, Moot R, Yi MC, Funke R, Sibley A, Stallings-Schmitt T, Oh DY, Chmielowski B, Abedi M, Yuan Y, Sosman JA, Lee SM, Schoenfeld AJ, Baltimore D, Heath JR, Franzusoff A, Ribas A, Rao AV, Mandl SJ. Non-viral precision T cell receptor replacement for personalized cell therapy. Nature. 2023 Mar;615(7953):687-696. doi: 10.1038/s41586-022-05531-1. Epub 2022 Nov 10.

Reference Type DERIVED
PMID: 36356599 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35537408 (View on PubMed)

Other Identifiers

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PACT-0101

Identifier Type: -

Identifier Source: org_study_id

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