Phase I/II Study of Autologous T Cells to Express T-Cell Receptors (TCRs) in Subjects With Solid Tumors

NCT ID: NCT05194735

Last Updated: 2025-11-10

Study Results

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

8 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-04-04

Study Completion Date

2023-08-14

Brief Summary

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A Phase I/II study of autologous T cells engineered using the Sleeping Beauty transposon/transposase system to express TCR(s) reactive against neoantigens in subjects with relapsed/refractory solid tumors

Detailed Description

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A Phase I/II study of autologous T cells engineered using the Sleeping Beauty transposon/transposase system to express TCR(s) reactive against neoantigens in subjects with relapsed/refractory solid tumors.

An HLA Typing and Tumor Neoantigen Mutation Testing Protocol (Protocol # TCR001-002) has been used to identify patients for potential enrollment into this Study Protocol. Subjects who have completed the HLA Typing and Tumor Neoantigen Mutation Testing Protocol, i.e., subjects for whom a TCR matching the subject's somatic mutation(s) and HLA type restriction combination is available in Alaunos' TCR library will be eligible for enrollment on this study.

The Phase I part of this study is a prospective, open-label, dose-escalation study of TCR-T cell drug product in patients with progressive or recurrent solid tumors who have failed standard therapy. The Phase II part is a prospective, open-label, single dose portion of the study. The Phase II part will begin once the MTD/RP2D in the Phase I part has been determined.

Subjects with one of the following histologically confirmed solid tumors will be included:

* Cohort 1: Gynecologic cancer (e.g., ovarian, endometrial)
* Cohort 2: Colorectal cancer
* Cohort 3: Pancreatic cancer
* Cohort 4: Non-small cell lung cancer (NSCLC); NSCLC includes but is not limited to squamous cell carcinoma, adenosquamous carcinoma or adenocarcinomas
* Cohort 5: Cholangiocarcinoma

Subject must have a tumor mutation and HLA typing combination that matches to at least one of the following TCRs in the Alaunos' library (mutation \& HLA type):

* KRAS G12D \& HLA-A\*11:01
* KRAS G12D \& HLA-C\*08:02
* KRAS G12V \& HLA-A\*11:01
* KRAS G12V \& HLA-C\*01:02
* TP53 R175H \& HLA-A\*02:01
* TP53 R175H \& HLA-DRB1\*13:01
* TP53 R248W \& HLA-A\*68:01
* TP53 Y220C \& HLA-A\*02:01
* TP53 Y220C \& HLA-DRB3\*02:02
* EGFR E746-A750del \& HLA-DPA1\*02:01, DPB1\*01:01

Conditions

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Gynecologic Cancer Colorectal Cancer Pancreatic Cancer Non-small Cell Lung Cancer Cholangiocarcinoma Ovarian Cancer Endometrial Cancer Ovarian Carcinoma Ovary Neoplasm Squamous Cell Lung Cancer Adenocarcinoma of Lung Adenosquamous Cell Lung Cancer

Keywords

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adoptive cell therapy neoantigen T cell receptor T lymphocyte TCR-engineered T cells cell therapy immunotherapy IL-2 Gene therapy

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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TCR-T Cell Drug Product

Phase I: Dose-escalation of TCR-T Cell Drug Product

Phase II: Single dose of TCR-T Cell Drug Product after MTD/RP2D determine in Phase I portion of the study

Group Type EXPERIMENTAL

Neoantigen specific TCR-T cell drug product

Intervention Type BIOLOGICAL

Phase I:

Ascending dose, single Infusion of TCR+ Cells

Phase II:

Single infusion at the RP2D

TCR-T Cell Drug Product with Aldesleukin (IL-2)

Phase I: Dose-escalation of TCR-T Cell Drug Product with Aldesleukin (IL-2)

Phase II: Single dose of TCR-T Cell Drug Product with Aldesleukin (IL-2) after MTD/RP2D determine in Phase I portion of the study

Group Type EXPERIMENTAL

Neoantigen specific TCR-T cell drug product

Intervention Type BIOLOGICAL

Phase I:

Ascending dose, single Infusion of TCR+ Cells

Phase II:

Single infusion at the RP2D

Aldesleukin (IL-2)

Intervention Type BIOLOGICAL

To support growth and activation of TCR-T cell drug product

Interventions

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Neoantigen specific TCR-T cell drug product

Phase I:

Ascending dose, single Infusion of TCR+ Cells

Phase II:

Single infusion at the RP2D

Intervention Type BIOLOGICAL

Aldesleukin (IL-2)

To support growth and activation of TCR-T cell drug product

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

1. Patients who have completed the HLA Typing and Tumor Neoantigen Identification Protocol (TCR001-002) and for whom a TCR(s) matching the subject's somatic mutation(s) and HLA type restriction combination is available in Alaunos' Clinical TCR library
2. Patients who have previously received at least one line of standard systemic therapy for their advanced/metastatic cancer and have either progressed, recurred, or were intolerant to the previous treatment. Specifically:

* Subgroup 1. Gynecologic cancers (i.e., ovarian or endometrial):

1. Ovarian cancer
2. Endometrial cancer
* Subgroup 2. Colorectal cancer
* Subgroup 3. Pancreatic cancer
* Subgroup 4. Non-small cell lung cancer (NSCLC)
* Subgroup 5. Cholangiocarcinoma
3. Patients must have evaluable or measurable disease per RECIST 1.1 with at least one lesion that can be measured that is not the biopsied lesion.
4. Patients must be able to provide written informed consent.
5. Patients must be age ≥ 18 years.
6. Clinical Performance Status of ECOG 0 or 1. Approval from the Alaunos Medical Monitor is required for ECOG of 2.
7. Patient must be willing and able to provide written informed consent for the long-term follow-up protocol (TCR001-202) for up to 15 years post TCR-T Cell drug product infusion per FDA requirements.
8. Adequate bone marrow reserves as assessed by the following hematology laboratory criteria:
9. Adequate major organ system function
10. A washout period must have elapsed since completion of any prior systemic therapy, and apheresis with guidelines as follows (windows other than what is listed below should be allowed only after consultation with the Medical Monitor); subjects' non-hematologic toxicities from any prior systemic therapy must have recovered to ≤ Grade 1 (with the exception of neuropathy and alopecia) or baseline prior to starting the protocol's therapy.
11. Patients may have undergone minor surgical procedures or limited-field radiotherapy provided any major organ toxicities have recovered to ≤ Grade 1.
12. Female patients must not be pregnant or breastfeeding.

Exclusion Criteria

1. Patients with known active CNS metastases
2. Concurrent systemic steroid therapy
3. Any form of primary immunodeficiency
4. Patients who have decreased immune competence
5. History of severe immediate hypersensitivity reaction to cyclophosphamide, fludarabine, aldesleukin or bendamustine
6. Severe chronic respiratory condition
7. History of a bleeding disorder or unexplained major bleeding diathesis
8. Arm B Criteria only: Clinically significant patient history which in the judgment of the principal investigator (PI) would compromise the subject's ability to tolerate high-dose aldesleukin;
9. Any major bronchial occlusion or bleeding not amenable to palliation.
10. Patients with psychiatric illness/social situations at the time of treatment that would limit compliance with study requirements.
11. Participants with known active, uncontrolled bacterial, fungal, or viral infection
12. Patients with a prior history or concurrent malignancy
13. Active unstable or clinically significant medical condition
14. History of any major cardiovascular conditions within the past 6 months
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Alaunos Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Scott Kopetz, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

MD Anderson

Locations

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MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 35537408 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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TCR001-201

Identifier Type: -

Identifier Source: org_study_id