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

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ClinicalTrials.gov Identifier: NCT03970382
Recruitment Status : Recruiting
First Posted : May 31, 2019
Last Update Posted : October 14, 2019
Sponsor:
Information provided by (Responsible Party):
PACT Pharma, Inc.

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 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 148 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 : December 2020
Estimated Study Completion Date : December 2022


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




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 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.



Information from the National Library of Medicine

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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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03970382


Contacts
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Contact: Clinical Operations 6505979464 clinicaltrials@pactpharma.com

Locations
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United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Ripa Martirosyan, MPH    626-218-2835    hmartirosyan@coh.org   
Principal Investigator: Mihaela Cristea, MD         
University of California, Los Angeles Not yet recruiting
Los Angeles, California, United States, 90024
Contact: Bartosz Chmielowski, MD       BChmielowski@mednet.ucla.edu   
Contact: Peter Hanna       phhanna@mednet.ucla.edu   
Principal Investigator: Bartosz Chmielowski, MD         
University of California, Irvine Medical Center Recruiting
Orange, California, United States, 92868
Contact: UCLA-UCI Alpha Stem Cell Clinic    949-824-3990    stemcell@uci.edu   
Principal Investigator: Samuel Ejadi, MD         
University of California, Davis Recruiting
Sacramento, California, United States, 95817
Contact: Mehrdad Abedi, MD    916-734-3772      
Principal Investigator: Mehrdad Abedi, MD         
University of California, San Diego Not yet recruiting
San Diego, California, United States, 92093
Principal Investigator: Sandip Patel, MD         
University of California, San Francisco Not yet recruiting
San Francisco, California, United States, 94158
Principal Investigator: David Oh, MD         
Sponsors and Collaborators
PACT Pharma, Inc.

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Responsible Party: PACT Pharma, Inc.
ClinicalTrials.gov Identifier: NCT03970382     History of Changes
Other Study ID Numbers: PACT-0101
First Posted: May 31, 2019    Key Record Dates
Last Update Posted: October 14, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Additional relevant MeSH terms:
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Neoplasms
Nivolumab
Antineoplastic Agents, Immunological
Antineoplastic Agents