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

NCT03970382SuspendedPHASE1INTERVENTIONAL

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.

Key Facts

Lead Sponsor

PACT Pharma, Inc.

Enrollment

21

Start Date

2019-07-03

Completion Date

2022-08-12

Study Type

INTERVENTIONAL

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

Interventions

NeoTCR-P1 adoptive cell therapynivolumabIL-2

Conditions

Solid Tumor

Eligibility

Age Range

18 Years+

Sex

ALL

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.

Outcome Measures

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 2 years

Feasibility of manufacturing NeoTCR-P1

Percent of screened patients that enroll on study and receive NeoTCR-P1

Time frame: 2 years

Secondary Outcomes

Maximum concentration of NeoTCR-P1 (Cmax) in the peripheral blood

Time frame: 2 years

Area-under-the-concentration-vs-time-curve (AUC) in the peripheral blood

Time frame: 28 days

Persistence of NeoTCR-P1 in samples of peripheral blood

Time frame: 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

ORR will be defined as Complete Response (CR) or Partial Response (PR) per RECIST v1.1, as determined by the investigator

Time frame: 2 years

Duration of Response mediated by neoTCR-P1 administered as a single agent or in combination with nivolumab to participants with solid tumors

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

Time frame: 2 years

Progression free survival (PFS) in participants with solid tumors following infusion of NeoTCR-P1 as a single agent or in combination with nivolumab

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

Time frame: 2 years

Overall survival (OS) in participants with solid tumors following infusion of NeoTCR-P1 as a single agent or in combination with nivolumab

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.

Time frame: 2 years

Locations

City of Hope, Duarte, United States

University of California, Los Angeles, Los Angeles, United States

University of California, Irvine Medical Center, Orange, United States

University of California, Davis, Sacramento, United States

University of California, San Francisco, San Francisco, United States

Northwestern University Medical Center, Chicago, United States

Memorial Sloan Kettering Cancer Center, New York, United States

Tennessee Oncology, Nashville, United States

Fred Hutchinson Cancer Research Center, Seattle, United States

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