Clinical trial NCT03970382: A Study of Gene Edited Autologous Neoantigen Targeted TCR T Cells With or Without Anti-PD-1 in Patients With Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE1
Conditions: Solid Tumor
Keywords: 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
Lead sponsor: PACT Pharma, Inc.
Sponsor class: INDUSTRY
First posted: 2019-05-31
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Incidence of adverse events as defined as DLTs
timeFrame: 28 days
measure: Number of participants with adverse events as a measure of safety and tolerability of NeoTCR-P1 or NeoTCR-P1 in combination with nivolumab
timeFrame: 2 years
measure: Maximum Tolerated Dose (MTD) of NeoTCR-P1
timeFrame: 2 years
measure: Feasibility of manufacturing NeoTCR-P1
timeFrame: 2 years
Secondary outcomes:
measure: Maximum concentration of NeoTCR-P1 (Cmax) in the peripheral blood
timeFrame: 2 years
measure: Area-under-the-concentration-vs-time-curve (AUC) in the peripheral blood
timeFrame: 28 days
measure: Persistence of NeoTCR-P1 in samples of peripheral blood
timeFrame: 2 years
measure: Objective Response Rate (ORR) in participants with solid tumors following infusion of NeoTCR-P1 as a single agent or in combination with nivolumab
timeFrame: 2 years
measure: Duration of Response mediated by neoTCR-P1 administered as a single agent or in combination with nivolumab to participants with solid tumors
timeFrame: 2 years
measure: Progression free survival (PFS) in participants with solid tumors following infusion of NeoTCR-P1 as a single agent or in combination with nivolumab
timeFrame: 2 years
measure: Overall survival (OS) in participants with solid tumors following infusion of NeoTCR-P1 as a single agent or in combination with nivolumab
timeFrame: 2 years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: Orange
country: United States
facility: University of California, Irvine Medical Center
state: California
city: Sacramento
country: United States
facility: University of California, Davis
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Chicago
country: United States
facility: Northwestern University Medical Center
state: Illinois
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
Study officials:
References:
citation: 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.