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

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Brief Title

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

Official Title

Phase I/II Study of Autologous T Cells Engineered Using the Sleeping Beauty System to Express T-Cell Receptors (TCRs) Reactive Against Cancer-specific Mutations in Subjects With Solid Tumors

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
    

Detailed Description

      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
    

Study Phase

Phase 1/Phase 2

Study Type

Interventional


Primary Outcome

Phase I: To define the incidence of dose limiting toxicity (DLT) and the maximum tolerated dose (MTD) or recommended phase II dose (RP2D) of T-Cell Receptor T cells

Secondary Outcome

 Phase I: To evaluate the feasibility of neoantigen-specific T-Cell Receptor T cells (herein referred to as TCR-T cells) manufacturing.

Condition

Gynecologic Cancer

Intervention

Neoantigen specific TCR-T cell drug product

Study Arms / Comparison Groups

 TCR-T Cell Drug Product
Description:  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

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

180

Start Date

April 2022

Completion Date

March 2029

Primary Completion Date

December 2025

Eligibility Criteria

        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
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Scott Kopetz, MD, PhD, 617-315-1790, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT05194735

Organization ID

TCR001-201


Responsible Party

Sponsor

Study Sponsor

Alaunos Therapeutics


Study Sponsor

Scott Kopetz, MD, PhD, Principal Investigator, MD Anderson


Verification Date

April 2022