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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
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
1 other identifier
interventional
21
1 country
9
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Jul 2019
Typical duration for phase_1
9 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 6, 2019
CompletedFirst Posted
Study publicly available on registry
May 31, 2019
CompletedStudy Start
First participant enrolled
July 3, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 12, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
August 12, 2022
CompletedAugust 18, 2022
August 1, 2022
3.1 years
May 6, 2019
August 16, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
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 Outcomes (7)
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
2 years
Duration of Response mediated by neoTCR-P1 administered as a single agent or in combination with nivolumab to participants with solid tumors
2 years
- +2 more secondary outcomes
Study Arms (3)
NeoTCR-P1
EXPERIMENTALSingle dose of NeoTCR-P1
NeoTCR-P1 plus nivolumab
EXPERIMENTALSingle dose of NeoTCR-P1 plus nivolumab 480mg IV every four weeks for up to 6 doses.
NeoTCR-P1 plus IL-2
EXPERIMENTALSingle dose of NeoTCR-P1 plus IL-2 500,000 IU/m2 SC twice daily (BID) for 7 days.
Interventions
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 is a human IgG4 anti-PD-1 monoclonal antibody
IL-2 is a biologic response modifier. It is a type of protein called a cytokine.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (9)
City of Hope
Duarte, California, 91010, United States
University of California, Los Angeles
Los Angeles, California, 90024, United States
University of California, Irvine Medical Center
Orange, California, 92868, United States
University of California, Davis
Sacramento, California, 95817, United States
University of California, San Francisco
San Francisco, California, 94158, United States
Northwestern University Medical Center
Chicago, Illinois, 60611, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Tennessee Oncology
Nashville, Tennessee, 37203, United States
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109, United States
Related Publications (2)
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.
PMID: 36356599DERIVEDLevy 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.
PMID: 35537408DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 6, 2019
First Posted
May 31, 2019
Study Start
July 3, 2019
Primary Completion
August 12, 2022
Study Completion
August 12, 2022
Last Updated
August 18, 2022
Record last verified: 2022-08
Data Sharing
- IPD Sharing
- Will not share