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
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 840
- 试验地点
- 21
- 主要终点
- Determine the recommended phase 2 dose of monotherapy and T- Plex combination TCR-Ts
研究概览
简要总结
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.
详细描述
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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must be at least 18 years.
- •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.
- •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.
- •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
- •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).
- •Eastern Cooperative Oncology Group (ECOG) Performance status 0-1 at screening.
- •Participants must be able to understand and be willing to give informed consent; decision-impaired adults may consent with their legally authorized representative.
- •At least 1 measurable lesion per modified Response Evaluation Criteria in Solid Tumors (RECIST) v1.
- •Adequate bone marrow and organ function.
排除标准
- •Medical or psychological conditions that would make the participant unsuitable candidate for cell therapy at the discretion of the PI.
- •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
- •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.
- •History of stroke or transient ischemic attack (TIA) within 6 months of enrollment
- •Systemic corticosteroid therapy >10 mg of prednisone daily or equivalent within 7 days of enrollment.
- •History of severe hypersensitivity to fludarabine or cyclophosphamide or study product excipients including human serum albumin, Cryostor (DMSO or Dextran 40), or Plasma-Lyte.
- •Untreated or symptomatic central nervous system (CNS) metastases or cytology proven carcinomatous meningitis.
- •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.
- •Presence of fungal, bacterial, viral, or other infection requiring anti-microbials for management.
- •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.
- •Participants who regularly require supplemental oxygen.
研究组 & 干预措施
Monotherapy Cohort A
TSC-204-A0201
干预措施: TSC-204-A0201 (Biological)
Monotherapy Cohort B
TSC-204-C0702
干预措施: TSC-204-C0702 (Biological)
Monotherapy Cohort C
TSC-200-A0201
干预措施: TSC-200-A0201 (Biological)
T-Plex Combination Cohort A + B
TSC-204-A0201 and TSC-204-C0702
干预措施: TSC-204-A0201 + TSC-204-C0702 (Biological)
T-Plex Combination Cohort B + C
TSC-204-C0702 and TSC-200-A0201
干预措施: TSC-204-A0201 + TSC-200-A0201 (Biological)
T-Plex Combination Cohort A + C
TSC-204-A0201 and TSC-200-A0201
干预措施: TSC-204-C0702 + TSC-200-A0201 (Biological)
Monotherapy Cohort D
TSC-203-A0201
干预措施: TSC-203-A0201 (Biological)
T-Plex Combination Cohort A + D
TSC-204-A0201 + TSC-203-A0201
干预措施: TSC-204-A0201 + TSC-203-A0201 (Biological)
T-Plex Combination Cohort B + D
TSC-204-C0702 + TSC-203-A0201
干预措施: TSC-204-C0702 + TSC-203-A0201 (Biological)
Monotherapy Cohort E
TSC-204-A0101
干预措施: TSC-204-A0101 (Biological)
Monotherapy Cohort F
TSC-201-B0702
干预措施: TSC-201-B0702 (Biological)
T-Plex Combination Cohort A + E
TSC-204-A0201 + TSC-204-A0101
干预措施: TSC-204-A0201 + TSC-204-A0101 (Biological)
T-Plex Combination Cohort A + F
TSC-204-A0201 + TSC-201-B0702
干预措施: TSC-204-A0201 + TSC-201-B0702 (Biological)
T-Plex Combination Cohort B + E
TSC-204-C0702 + TSC-204-A0101
干预措施: TSC-204-C0702 + TSC-204-A0101 (Biological)
T-Plex Combination Cohort B + F
TSC-204-C0702 + TSC-201B0702
干预措施: TSC-204-C0702 + TSC-201-B0702 (Biological)
T-Plex Combination Cohort C + D
TSC-200-A0201 + TSC-203-A0201
干预措施: TSC-200-A0201 + TSC-203-A0201 (Biological)
T-Plex Combination Cohort C + E
TSC-200-A0201 + TSC-204-A0101
干预措施: TSC-200-A0201 + TSC-204-A0101 (Biological)
T-Plex Combination Cohort C + F
TSC-200-A0201 + TSC-201B0702
干预措施: TSC-200-A0201 + TSC-201-B0702 (Biological)
T-Plex Combination Cohort D + E
TSC-203-A0201 + TSC-204A0101
干预措施: TSC-203-A0201 + TSC-204-A0101 (Biological)
T-Plex Combination Cohort D + F
TSC-203-A0201 + TSC-201B0702
干预措施: TSC-203-A0201 + TSC-201-B0702 (Biological)
T-Plex Combination Cohort E + F
TSC-204-A0101 + TSC-201-B0702
干预措施: TSC-204-A0101 (Biological)
T-Plex Combination Cohort E + F
TSC-204-A0101 + TSC-201-B0702
干预措施: TSC-201-B0702 (Biological)
Monotherapy Cohort G
TSC-202-A0201
干预措施: TSC-202-A0201 (Biological)
T-Plex Combination Cohort A + G
TSC-204-A0201 + TSC-202-A0201
干预措施: TSC-204-A0201 + TSC-202-A0201 (Biological)
T-Plex Combination Cohort B + G
TSC-204-C0702 + TSC-202-A0201
干预措施: TSC-204-C0702 + TSC-202-A0201 (Biological)
T-Plex Combination Cohort C+ G
TSC-200-A0201 + TSC-202-A0201
干预措施: TSC-200-A0201 + TSC-202-A0201 (Biological)
T-Plex Combination Cohort D + G
TSC-203-A0201 + TSC-202-A0201
干预措施: TSC-203-A0201 + TSC-202-A0201 (Biological)
T-Plex Combination Cohort E + G
TSC-204-A0101 + TSC-202-A0201
干预措施: TSC-204-A0101 + TSC-202-A0201 (Biological)
T-Plex Combination Cohort F + G
TSC-201-B0702 + TSC-202-A0201
干预措施: TSC-201-B0702 + TSC-202-A0201 (Biological)
结局指标
主要结局
Determine the recommended phase 2 dose of monotherapy and T- Plex combination TCR-Ts
时间窗: Up to 12 months
Frequency and severity of DLTs, AEs and SAEs
Evaluate the safety of monotherapy and T- Plex combination TCR-Ts
时间窗: 28 days
Number of subjects with dose limiting toxicities (DLT)
次要结局
- Investigate preliminary anti-tumor activity of monotherapy and T- Plex combination TCR-Ts(Up to 12 months)
- Investigate the feasibility of repeat dosing of monotherapy and T- Plex combination TCR-Ts(Up to 12 months)