A Phase 1a/1b Dose Escalation/Expansion Study of TTX-080, an HLA-G Antagonist, as Monotherapy and in Combination With Pembrolizumab, Cetuximab or FOLFIRI Plus Cetuximab in Patients With Advanced Solid Refractory/Resistant Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 240
- 试验地点
- 104
- 主要终点
- 1. To determine the anti-tumor activity of TTX-080 by objective response rate [complete response + partial response) for each tumor arm per RECIST 1.1
研究概览
简要总结
TTX-080-001 is a Phase 1, open label, dose escalation and dose expansion clinical study to determine the safety, tolerability, and recommended Phase 2 dose of TTX-080 monotherapy (HLA-G inhibitor) and in combination with either pembrolizumab (PD-1 inhibitor), cetuximab (EGFR inhibitor) or FOLFIRI plus cetuximab (EGFR inhibitor) in patients with advanced refractory / resistant solid malignancies including metastatic colorectal cancer (mCRC) patients.
详细描述
TTX-080 is a fully human mAb designed to block the interaction of HLA-G with its known ligands, ILT2 and ILT4 molecules. The Phase 1a was an open label, multicenter, dose escalation clinical trial to determine the safety, tolerability, MTD or OBD, and the RP2D of TTX-080 when administered as a single agent. The Phase 1b is a dose expansion of TTX-080 monotherapy and in combination with either pembrolizumab or cetuximab in adult subjects with advanced refractory/resistant solid malignancies, including Head and Neck squamous cell carcinoma (HNSCC), Non-Small Cell Lung Cancer (NSCLC), Colorectal cancer (CRC), triple negative breast cancer (TNBC), renal cell carcinoma (RCC), and acral melanoma. Additionally, the Phase 1b includes randomized arms with TTX-080 in combination with FOLFIRI plus cetuximab compared to FOLFIRI plus cetuximab in metastatic Colorectal cancer. The study will seek to evaluate the pharmacokinetics and immunogenicity of TTX-080, and characterize the anti-tumor activity of TTX-080 as a monotherapy and in combination with pembrolizumab, cetuximab or FOLFIRI plus cetuximab. Only arm 9 and 10 are currently open to enrollment.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Abbreviated Inclusion Criteria:
- •Subject with histological diagnosis of advanced/metastatic cancer [currently enrolling in CRC only]
- •Age 18 years or older, is willing and able to provide informed consent
- •Evidence of measurable disease
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 AND life expectancy of at least 12 weeks
- •Abbreviated
排除标准
- •History of allergy or hypersensitivity to study treatment components. Subjects with a history of severe hypersensitivity reaction to any monoclonal antibody
- •Use of an investigational agent within 28 days prior to the first dose of study treatment and throughout the study
- •Receiving high-dose systemic steroid therapy or any other form of immunosuppressive therapy
- •History of severe autoimmune disease
- •Uncontrolled intercurrent illness or other active malignancy requiring ongoing treatment
研究组 & 干预措施
Phase 1b, Dose Expansion: TTX-080 in combination with pembrolizumab (HNSCC)
Arm 1 will enroll subjects with advanced/metastatic, prior checkpoint inhibitor treated Head and Neck Squamous Cell Carcinoma (HNSCC) [Closed]
干预措施: TTX-080 (Drug)
Phase 1b, Dose Expansion: TTX-080 in combination with pembrolizumab (HNSCC)
Arm 1 will enroll subjects with advanced/metastatic, prior checkpoint inhibitor treated Head and Neck Squamous Cell Carcinoma (HNSCC) [Closed]
干预措施: pembrolizumab (Drug)
Phase 1b, Dose Expansion: TTX-080 in combination with cetuximab (HNSCC)
Arm 2 will enroll subjects with advanced/metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) [Closed]
干预措施: TTX-080 (Drug)
Phase 1b, Dose Expansion: TTX-080 in combination with cetuximab (HNSCC)
Arm 2 will enroll subjects with advanced/metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) [Closed]
干预措施: cetuximab (Drug)
Phase 1b, Dose Expansion: TTX-080 in combination with cetuximab (CRC), prior anti-EGFR therapy
Arm 4 will enroll subjects with advanced/metastatic MSI-L/MSS, KRAS wild-type colorectal cancer (CRC) who have progressed on a prior anti-EGFR therapy [Closed]
干预措施: cetuximab (Drug)
TTX-080 in combination with FOLFIRI plus cetuximab
Arm 9: TTX-080 in combination with FOLFIRI plus cetuximab Randomized Arms in subjects with metastatic RAS, BRAF and HER2 wild type colorectal cancer (CRC) who have been received oxaliplatin and 5-FU based chemotherapy in the first line or adjuvant (relapse within 6 months) setting. Prior bevacizumab allowed. No prior EGFR inhibitor.
干预措施: FOLFIRI (Drug)
FOLFIRI plus cetuximab
Arm 10: FOLFIRI plus cetuximab Randomized Arms in subjects with metastatic RAS, BRAF and HER2 wild type colorectal cancer (CRC) who have been received oxaliplatin and 5-FU based chemotherapy in the first line or adjuvant (relapse within 6 months) setting. Prior bevacizumab allowed. No prior EGFR inhibitor.
干预措施: cetuximab (Drug)
Phase 1a, Monotherapy Dose Escalation
干预措施: TTX-080 (Drug)
Phase 1b, Dose Expansion: TTX-080 monotherapy (CRC)
Arm 3 will enroll subjects with advanced/metastatic colorectal cancer (CRC) [Closed]
干预措施: TTX-080 (Drug)
Phase 1b, Dose Expansion: TTX-080 in combination with cetuximab (CRC), no prior anti-EGFR therapy
Arm 5 will enroll subjects with advanced/metastatic MSI-L/MSS, KRAS wild type colorectal cancer (CRC) who have not received a prior anti-EGFR therapy [Closed]
干预措施: cetuximab (Drug)
Phase 1b, Dose Expansion: TTX-080 in combination with pembrolizumab (NSCLC)
Arm 7 will enroll subjects with advanced/metastatic prior checkpoint inhibitor treated non-small cell lung cancer (NSCLC) [Closed]
干预措施: pembrolizumab (Drug)
FOLFIRI plus cetuximab
Arm 10: FOLFIRI plus cetuximab Randomized Arms in subjects with metastatic RAS, BRAF and HER2 wild type colorectal cancer (CRC) who have been received oxaliplatin and 5-FU based chemotherapy in the first line or adjuvant (relapse within 6 months) setting. Prior bevacizumab allowed. No prior EGFR inhibitor.
干预措施: FOLFIRI (Drug)
Phase 1b, Dose Expansion: TTX-080 in combination with cetuximab (CRC), prior anti-EGFR therapy
Arm 4 will enroll subjects with advanced/metastatic MSI-L/MSS, KRAS wild-type colorectal cancer (CRC) who have progressed on a prior anti-EGFR therapy [Closed]
干预措施: TTX-080 (Drug)
Phase 1b, Dose Expansion: TTX-080 in combination with cetuximab (CRC), no prior anti-EGFR therapy
Arm 5 will enroll subjects with advanced/metastatic MSI-L/MSS, KRAS wild type colorectal cancer (CRC) who have not received a prior anti-EGFR therapy [Closed]
干预措施: TTX-080 (Drug)
Phase 1b, Dose Expansion: TTX-080 monotherapy (NSCLC)
Arm 6 will enroll subjects with advanced/metastatic non-small cell lung cancer (NSCLC) [Closed]
干预措施: TTX-080 (Drug)
Phase 1b, Dose Expansion: TTX-080 in combination with pembrolizumab (NSCLC)
Arm 7 will enroll subjects with advanced/metastatic prior checkpoint inhibitor treated non-small cell lung cancer (NSCLC) [Closed]
干预措施: TTX-080 (Drug)
Phase 1b, Dose Expansion: TTX-080 as monotherapy OR in combination with pembrolizumab
Arm 8: TTX-080 monotherapy:
- Advanced/metastatic, prior checkpoint inhibitor treated renal cell carcinoma with predominance of clear cell component
- Advanced/metastatic acral melanoma
Arm 8: TTX-080 in combination with pembrolizumab:
• Advanced/metastatic triple-negative breast cancer (estrogen and progesterone receptor negative and HER2 negative) who has received a prior checkpoint inhibitor
[Closed]
干预措施: TTX-080 (Drug)
Phase 1b, Dose Expansion: TTX-080 as monotherapy OR in combination with pembrolizumab
Arm 8: TTX-080 monotherapy:
- Advanced/metastatic, prior checkpoint inhibitor treated renal cell carcinoma with predominance of clear cell component
- Advanced/metastatic acral melanoma
Arm 8: TTX-080 in combination with pembrolizumab:
• Advanced/metastatic triple-negative breast cancer (estrogen and progesterone receptor negative and HER2 negative) who has received a prior checkpoint inhibitor
[Closed]
干预措施: pembrolizumab (Drug)
TTX-080 in combination with FOLFIRI plus cetuximab
Arm 9: TTX-080 in combination with FOLFIRI plus cetuximab Randomized Arms in subjects with metastatic RAS, BRAF and HER2 wild type colorectal cancer (CRC) who have been received oxaliplatin and 5-FU based chemotherapy in the first line or adjuvant (relapse within 6 months) setting. Prior bevacizumab allowed. No prior EGFR inhibitor.
干预措施: cetuximab (Drug)
TTX-080 in combination with FOLFIRI plus cetuximab
Arm 9: TTX-080 in combination with FOLFIRI plus cetuximab Randomized Arms in subjects with metastatic RAS, BRAF and HER2 wild type colorectal cancer (CRC) who have been received oxaliplatin and 5-FU based chemotherapy in the first line or adjuvant (relapse within 6 months) setting. Prior bevacizumab allowed. No prior EGFR inhibitor.
干预措施: TTX-080 (Drug)
结局指标
主要结局
1. To determine the anti-tumor activity of TTX-080 by objective response rate [complete response + partial response) for each tumor arm per RECIST 1.1
时间窗: Up to 48 months
次要结局
- Duration of Response, Progression Free Survival per RECIST 1.1(Up to 48 months)
- Overall Survival(Up to 48 months)
- Tolerability: The number of cycles of TTX-080 received by patients before discontinuing due to unmanageable drug reactions(Up to 48 months)
- Serum levels of Anti Drug Antibody against TTX-080(Up to 48 months)
- Cmax: Maximum Observed Plasma Concentration for TTX-080(Up to 48 months)
- Tmax: Time to Reach the Cmax for TTX-080(Up to 48 months)
- AUC(0-t): Area Under the Plasma Concentration-time Curve From Zero Time to the Last Measurable Point for TTX-080(Up to 48 months)
- AUC(0-Inf): Area Under the Plasma Concentration-time Curve From Zero to Infinity for TTX-080(Up to 48 months)
- Adverse events (AEs) as characterized by the incidence, type, frequency, severity (graded according to NCI-CTCAE v5.0), timing, seriousness, and relationship to investigational product, and/or combination therapy, and/or individual approved therapies(Up to 48 months)