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
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
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 4, 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, 832-622-1699, [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
March 2023