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

Solid Tumor Clinical Trial

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

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT03970382
• Other study ID #: PACT-0101
• Status: Suspended
• Phase: Phase 1
• Start date: July 3, 2019
• Est. completion date: August 12, 2022

Study information

• Verified date: August 2022
• Source: PACT Pharma, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 21
• Est. completion date: August 12, 2022
• Est. primary completion date: August 12, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumor

Intervention

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.
• nivolumab
Nivolumab is a human IgG4 anti-PD-1 monoclonal antibody
• IL-2
IL-2 is a biologic response modifier. It is a type of protein called a cytokine.

Locations

Country	Name	City	State
United States	Northwestern University Medical Center	Chicago	Illinois
United States	City of Hope	Duarte	California
United States	University of California, Los Angeles	Los Angeles	California
United States	Tennessee Oncology	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of California, Irvine Medical Center	Orange	California
United States	University of California, Davis	Sacramento	California
United States	University of California, San Francisco	San Francisco	California
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
PACT Pharma, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	Feasibility of manufacturing NeoTCR-P1	Percent of screened patients that enroll on study and receive NeoTCR-P1	2 years
Secondary	Maximum concentration of NeoTCR-P1 (Cmax) in the peripheral blood		2 years
Secondary	Area-under-the-concentration-vs-time-curve (AUC) in the peripheral blood		28 days
Secondary	Persistence of NeoTCR-P1 in samples of peripheral blood		2 years
Secondary	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	2 years
Secondary	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	2 years
Secondary	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	2 years
Secondary	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.	2 years