Clinical trial NCT05973487: A Basket Study of Customized Autologous TCR-T Cell Therapies in Patients With Locally Advanced (Unresectable) or Metastatic Solid Tumors
Official title: A Phase 1 Basket Study Evaluating the Safety and Feasibility of T-Plex, Autologous Customized T Cell Receptor-Engineered T Cells Targeting Multiple Peptide/HLA Antigens in Participants With Antigen-positive Locally Advanced (Unresectable) or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Head and Neck Cancer
Cervical Cancer
Non-small Cell Carcinoma
Melanoma
Ovarian Cancer
Anogenital Cancers
HPV - Anogenital Human Papilloma Virus Infection
HPV-Related Cervical Carcinoma
HPV-Related Carcinoma
HPV-Related Squamous Cell Carcinoma
HPV-Related Malignancy
HPV-Related Adenocarcinoma
HPV Positive Oropharyngeal Squamous Cell Carcinoma
HPV-Related Adenosquamous Carcinoma
HPV-Associated Vaginal Adenocarcinoma
HPV-Related Endocervical Adenocarcinoma
HPV-Related Anal Squamous Cell Carcinoma
HPV-Related Verrucous Carcinoma
HPV-Related Penile Squamous Cell Carcinoma
HPV-Related Vulvar Squamous Cell Carcinoma
HPV Positive Rectal Squamous Cell Carcinoma
Keywords: HPV16 E7
MAGE-A1
TCR-T Therapy
Cell Therapy
Immunotherapy
TScan Therapeutics
TSCAN-002
TSCAN-003
PRAME
MAGE-C2
MAGE-A4
Lead sponsor: TScan Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2023-08-03
Enrollment: 840
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: TScan Therapeutics is developing cellular therapies across multiple solid tumors in which autologous participant-derived engeneered T cells are engineered to express a T cell receptor that recognizes cancer-associated antigens presented on specific Human Leukocyte Antigen (HLA) molecules.

This is a multi-center, non-randomized, multi-arm, open-label, basket study evaluating the safety and preliminary efficacy of single and repeat dose regimens of TCR'Ts as monotherapies and as T-Plex combinations after lymphodepleting chemotherapy in participants with locally advanced, metastatic solid tumors disease.

Detailed description: Participants will be screened in a separate screening study, TSCAN-003 (NCT05812027), to assess their HLA type, tumor-associated antigen (TAA) expression and loss of heterozygosity (LOH) status. The results of these tests will be used to determine initial eligibility in this study.

Depending on the genetic type, participants will be assigned to one of the following study groups:

Monotherapy:

* COHORT A: TSC-204-A0201 targeting MAGE-A1 on HLA-A\*02:01
* COHORT B: TSC-204-C0702 targeting MAGE-A1 on HLA-C\*07:02
* COHORT C: TSC-200-A0201 targeting HPV16 E7 on HLA-A\*02:01
* COHORT D: TSC-203-A0201 targeting PRAME on HLA-A\*02:01
* COHORT E: TSC-204-A0101 targeting MAGE-A1 on HLA-A\*01:01
* COHORT F: TSC-201-B0702 targeting MAGE-C2 on HLA-B\*07:02
* COHORT G: TSC-202-A0201 targeting MAGE-A4 on HLA-A\*02:01

T-Plex Combination:

* COHORT AB: TSC-204-A0201 + TSC-204-C0702
* COHORT AC: TSC-204-A0201 + TSC-200-A0201
* COHORT AD: TSC-204-A0201 + TSC-203-A0201
* COHORT AE: TSC-204-A0201 + TSC-204-A0101
* COHORT AF: TSC-204-A0201 + TSC-201-B0702
* COHORT BC: TSC-204-C0702 + TSC-200-A0201
* COHORT BD: TSC-204-C0702 + TSC-203-A0201
* COHORT BE: TSC-204-C0702 + TSC-204-A0101
* COHORT BF: TSC-204-C0702 + TSC-201-B0702
* COHORT CD: TSC-200-A0201 + TSC-203-A0201
* COHORT CE: TSC-200-A0201 + TSC-204-A0101
* COHORT CF: TSC-200-A0201 + TSC-201-B0702
* COHORT DE: TSC-203-A0201 + TSC-204-A0101
* COHORT DF: TSC-203-A0201 + TSC-201-B0702
* COHORT EF: TSC-204-A0101 + TSC-201-B0702
* COHORT AG: TSC-204-A0201 + TSC-202-A0201
* COHORT BG: TSC-204-C0702 + TSC-202-A0201
* COHORT CG: TSC-200-A0201 + TSC-202-A0201
* COHORT DG: TSC-203-A0201 + TSC-202-A0201
* COHORT EG: TSC-204-A0101 + TSC-202-A0201
* COHORT FG: TSC-201-B0702 + TSC-202-A0201

Participants will undergo leukapheresis to collect cells to manufacture the TCR-T products. They will then undergo lymphodepletion and receive one or two doses of the TCR-T cell therapy product as a monotherapy or part of a combination of TCR-Ts (referred to as T-Plex combinations in this study).

Eligibility criteria: Inclusion Criteria:

1. Must be at least 18 years.
2. Locally advanced (unresectable) or metastatic solid tumor for which there are no available curative treatment options, after failure of the standard of care systemic therapies for that particular indication.
3. Solid tumors, including but not limited to non-nasopharyngeal head and neck cancer, non-small cell lung cancer, cutaneous melanoma, cervical cancer, ovarian cancer, anal cancer and genital cancers. Other tumor types may be permitted if approved by TScan.
4. Participants must express one of the following HLA types, as assessed by a qualified genomics assay in screening study TSCAN-003: HLA-B\*07:02, HLA-A\*01:01, HLA-C\*07:02 and/or HLA-A\*02:01
5. Tumor must express one or more of the following: MAGE-A1, MAGE-A4, MAGE-C2, PRAME and HPV16 assessed in the last 8 months in screening study TSCAN-003 (NCT05812027).
6. Eastern Cooperative Oncology Group (ECOG) Performance status 0-1 at screening.
7. Participants must be able to understand and be willing to give informed consent; decision-impaired adults may consent with their legally authorized representative.
8. At least 1 measurable lesion per modified Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
9. Adequate bone marrow and organ function.

Exclusion Criteria:

1. Medical or psychological conditions that would make the participant unsuitable candidate for cell therapy at the discretion of the PI.
2. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, cardiac arrhythmia requiring antiarrhythmic or procedure, or other clinically significant cardiac disease within 12 months of enrollment
3. Have a history of ASTCT Grade 4 CRS, Grade 3 or greater ICANS, or Grade 3 or greater IECHS. Participants with a history of lower grade CRS, ICANS, or IECHS may be eligible, pending review and approval by the Medical Monitor.
4. History of stroke or transient ischemic attack (TIA) within 6 months of enrollment
5. Systemic corticosteroid therapy \>10 mg of prednisone daily or equivalent within 7 days of enrollment.
6. History of severe hypersensitivity to fludarabine or cyclophosphamide or study product excipients including human serum albumin, Cryostor (DMSO or Dextran 40), or Plasma-Lyte.
7. Untreated or symptomatic central nervous system (CNS) metastases or cytology proven carcinomatous meningitis.
8. Concurrent receipt of another anti-cancer therapy. Have a history of acute mental status changes of unknown etiology within 6 months prior to enrollment, or any neurological or neurodegenerative disorder (e.g., Parkinson disease, Huntington disease, uncontrolled seizure disorder) that may increase the risk for or confound the assessment of neurotoxicity.
9. Presence of fungal, bacterial, viral, or other infection requiring anti-microbials for management.
10. Tumors that have HLA LOH using a central lab clinical trial assay of HLAs addressed by the monotherapy and/or T-Plex combination TCR-Ts in the protocol and have no available TCR-T options for intact HLAs in the participant's tumor.
11. Participants who regularly require supplemental oxygen.

Primary outcomes:
measure: Evaluate the safety of monotherapy and T- Plex combination TCR-Ts
timeFrame: 28 days
measure: Determine the recommended phase 2 dose of monotherapy and T- Plex combination TCR-Ts
timeFrame: Up to 12 months
Secondary outcomes:
measure: Investigate preliminary anti-tumor activity of monotherapy and T- Plex combination TCR-Ts
timeFrame: Up to 12 months
measure: Investigate the feasibility of repeat dosing of monotherapy and T- Plex combination TCR-Ts
timeFrame: Up to 12 months
Other outcomes:
measure: To measure the persistence of T-Plex TCR-T cells in the peripheral blood with single and repeat doses
timeFrame: Up to 24 months
measure: To measure the infiltration of T-Plex TCR-T cells into tumors in post-treatment biopsies
timeFrame: Up to 24 months
measure: To measure the immune activation markers in the tumor after single and repeated doses
timeFrame: Up to 24 months
Locations:
city: Scottsdale
country: United States
facility: HonorHealth Research and Innovation Institute
state: Arizona
city: San Diego
country: United States
facility: University of California San Diego
state: California
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Hollywood
country: United States
facility: Memorial Healthcare System
state: Florida
city: Miami
country: United States
facility: University of Miami, Sylvester Comprehensive Cancer Center
state: Florida
city: Orlando
country: United States
facility: Orlando Health
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota Masonic Cancer Center
state: Minnesota
city: New York
country: United States
facility: Columbia University Herbert Irving Comprehensive Cancer Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Cleveland
country: United States
facility: The Cleveland Clinic
state: Ohio
city: Oklahoma City
country: United States
facility: OU Health Stephenson Cancer Center
state: Oklahoma
city: Portland
country: United States
facility: Providence Cancer Institute Franz Clinic
state: Oregon
city: Pittsburgh
country: United States
facility: Allegheny Hospitals Network
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
Study officials:
affiliation: TScan Therapeutics
name: Dawn Pinchasik, MD
role: STUDY_DIRECTOR
References: