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

NCT05194735 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: TCR001-201
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

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

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

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Treatment-Emergent Adverse Events

  Treatment-emergent adverse events (TEAEs) were defined as any adverse event that began or worsened after initiation of lymphodepletion and up to 28 days following TCR-T cell infusion. TEAEs were coded using MedDRA and summarized by system organ class and preferred term, severity, and relationship to study treatment. Participants were followed for delayed or ongoing toxicities for up to 1 year.

  From initiation of lymphodepletion through Day 28 after TCR-T cell infusion, and through long-term follow-up for up to 1 year.

• Frequency of Dose Limiting Toxicities

  Number of participants experiencing DLTs, defined as specific adverse events attributable to the TCR-T cell drug product occurring within the first 28 days of infusion. DLTs include, but are not limited to, Grade 4 neutropenia lasting ≥ 14 days, Grade 4 thrombocytopenia, Grade 3 thrombocytopenia with significant bleeding, and ≥ Grade 3 febrile neutropenia with hemodynamic compromise. Non-hematologic DLTs include Grade 3 or 4 Cytokine Release Syndrome (CRS) that does not improve to Grade ≤ 2 within 72 hours, and Grade 3 Immune-effector cell-associated neurotoxicity syndrome (ICANS) that does not resolve to Grade ≤ 2 within 7 days, among others. The severity of adverse events will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.

  From Day 0 to Day 28 post TCR-T cell drug product infusion.

• Determination of Maximum Tolerated Dose (MTD) or Recommended Phase II Dose (RP2D)

  The MTD and/or RP2D was to be determined based on dose-limiting toxicities observed during the dose-escalation phase. The planned definition required ≥2 patients at a given dose level to experience a DLT to declare that dose not tolerated.

  From Day 0 to Day 28 post TCR-T cell drug product infusion.

Secondary Outcomes (3)

• Feasibility of TCR-T Cell Drug Product Manufacturing

  From apheresis collection to the release of the final TCR-T cell drug product for infusion, estimated to be approximately 5 weeks

• TCR-T Cell Persistence

  Baseline through Month 18 post-infusion.

• Percent Change in TCR-T Cell Count From Post Dose to Day 28

  Post-dose through Day 28

Study Arms (2)

TCR-T Cell Drug Product

EXPERIMENTAL

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

Biological: Neoantigen specific TCR-T cell drug product

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

EXPERIMENTAL

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

Biological: Neoantigen specific TCR-T cell drug product; Biological: Aldesleukin (IL-2)

Interventions

Neoantigen specific TCR-T cell drug product BIOLOGICAL

Phase I: Ascending dose, single Infusion of TCR+ Cells Phase II: Single infusion at the RP2D

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

Aldesleukin (IL-2) BIOLOGICAL

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

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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):
• Ovarian cancer
• Endometrial cancer
• Subgroup 2. Colorectal cancer
• Subgroup 3. Pancreatic cancer
• Subgroup 4. Non-small cell lung cancer (NSCLC)
• Subgroup 5. Cholangiocarcinoma
• 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.
• Patients must be able to provide written informed consent.
• Patients must be age ≥ 18 years.
• Clinical Performance Status of ECOG 0 or 1. Approval from the Alaunos Medical Monitor is required for ECOG of 2.
• 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.
• Adequate bone marrow reserves as assessed by the following hematology laboratory criteria:

You may not qualify if:

• Patients with known active CNS metastases
• Concurrent systemic steroid therapy
• Any form of primary immunodeficiency
• Patients who have decreased immune competence
• History of severe immediate hypersensitivity reaction to cyclophosphamide, fludarabine, aldesleukin or bendamustine
• Severe chronic respiratory condition
• History of a bleeding disorder or unexplained major bleeding diathesis
• 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;
• Any major bronchial occlusion or bleeding not amenable to palliation.
• Patients with psychiatric illness/social situations at the time of treatment that would limit compliance with study requirements.
• Participants with known active, uncontrolled bacterial, fungal, or viral infection
• Patients with a prior history or concurrent malignancy
• Active unstable or clinically significant medical condition
• History of any major cardiovascular conditions within the past 6 months

Sponsors & Collaborators

• Alaunos Therapeutics: lead

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• 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.

  PMID: 35537408 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms; Pancreatic Neoplasms; Carcinoma, Non-Small-Cell Lung; Cholangiocarcinoma; Ovarian Neoplasms; Endometrial Neoplasms; Adenocarcinoma of Lung

Interventions

aldesleukin; Interleukin-2

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Gonadal Disorders; Uterine Neoplasms; Uterine Diseases

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Results Point of Contact

• Title: Jaymes Holland
• Organization: Alaunos Therapeutics, Inc.

jholland@alaunos.com

6502732627

Study Officials

• Scott Kopetz, MD, PhD

  MD Anderson

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2021
• First Posted: January 18, 2022
• Study Start: April 4, 2022
• Primary Completion: August 14, 2023
• Study Completion: August 14, 2023
• Last Updated: November 10, 2025
• Results First Posted: November 10, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)