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

Sponsor

PACT Pharma, Inc. (Industry)

Overall Status

Suspended

CT.gov ID

NCT03970382

Collaborator

(none)

Enrollment

Locations

Arms

37.3

Anticipated Duration (Months)

2.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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 Biological: IL-2	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

21 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 :

Jul 3, 2019

Anticipated Primary Completion Date :

Aug 12, 2022

Anticipated Study Completion Date :

Aug 12, 2022

Arms and Interventions

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 Names: Opdivo
Experimental: NeoTCR-P1 plus IL-2 Single dose of NeoTCR-P1 plus IL-2 500,000 IU/m2 SC twice daily (BID) for 7 days.	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: IL-2 IL-2 is a biologic response modifier. It is a type of protein called a cytokine. Other Names: Proleukin aldesleukin interleukin-2

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

Biological: nivolumab

Nivolumab is a human IgG4 anti-PD-1 monoclonal antibody

Other Names:

Opdivo

Experimental: NeoTCR-P1 plus IL-2

Single dose of NeoTCR-P1 plus IL-2 500,000 IU/m2 SC twice daily (BID) for 7 days.

Biological: NeoTCR-P1 adoptive cell therapy

Biological: IL-2

IL-2 is a biologic response modifier. It is a type of protein called a cytokine.

Other Names:

Proleukin

aldesleukin

interleukin-2

Outcome Measures

Primary Outcome Measures

Incidence of adverse events as defined as DLTs [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 without or with IL-2, or in combination with nivolumab.
Number of participants with adverse events as a measure of safety and tolerability of NeoTCR-P1 or NeoTCR-P1 in combination with nivolumab [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.
Maximum Tolerated Dose (MTD) of NeoTCR-P1 [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.
Feasibility of manufacturing NeoTCR-P1 [2 years]
Percent of screened patients that enroll on study and receive NeoTCR-P1

Secondary Outcome Measures

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]
ORR will be defined as Complete Response (CR) or Partial Response (PR) per RECIST v1.1, as determined by the investigator
Duration of Response mediated by neoTCR-P1 administered as a single agent or in combination with nivolumab to participants with solid tumors [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
Progression free survival (PFS) in participants with solid tumors following infusion of NeoTCR-P1 as a single agent or in combination with nivolumab [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
Overall survival (OS) in participants with solid tumors following infusion of NeoTCR-P1 as a single agent or in combination with nivolumab [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope	Duarte	California	United States	91010
2	University of California, Los Angeles	Los Angeles	California	United States	90024
3	University of California, Irvine Medical Center	Orange	California	United States	92868
4	University of California, Davis	Sacramento	California	United States	95817
5	University of California, San Francisco	San Francisco	California	United States	94158
6	Northwestern University Medical Center	Chicago	Illinois	United States	60611
7	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
8	Tennessee Oncology	Nashville	Tennessee	United States	37203
9	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109