A Phase 1B, Multicenter, Open-Label Study of the Safety and Efficacy of CHS-114 in Combination With Toripalimab With or Without Other Treatments in Participants With Advanced or Metastatic Solid Tumors (TREGCHECK 102)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 154
- 试验地点
- 51
- 主要终点
- Number of Participants With Treatment-emergent Adverse Events (TEAEs)
研究概览
简要总结
The main purpose of this study is to evaluate the safety and preliminary efficacy of CHS-114 in combination with toripalimab and/or other standard of care (SOC) compound(s) in participants with advanced or metastatic solid tumors.
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
- •At least 1 measurable lesion based on RECIST v1.1 as determined by the Investigator.
- •Resolved acute effects of any prior therapy to baseline severity or Grade 1 in accordance with National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) v5.0, except for adverse events (AEs) not constituting a safety risk per Investigator judgement.
- •Cohort A (2L Gastric, Gastro-esophageal-junction [GEJ], Esophageal Adenocarcinoma [EAC]) Specific Inclusion Criteria:
- •Histologically or cytologically documented unresectable, locally advanced or metastatic gastric, GEJ, or esophageal adenocarcinoma that is human epidermal growth factor receptor 2 (HER2) - negative and microsatellite stable (MSS)/proficient mismatch repair (pMMR).
- •Progressed during or after first line systemic therapy that includes a platinum and fluoropyrimidine doublet with or without anti-programmed death receptor 1 (PD-1)/programmed death ligand 1 (PD-L1)-directed therapy (that is, in the second line setting).
- •Consent to provide tumor tissue samples (baseline and on-treatment) is required for enrollment.
- •Cohort B (2L Esophageal Squamous Cell Carcinoma [ESCC]) - Specific Inclusion Criteria:
- •Histologically or cytologically documented unresectable, locally advanced or metastatic ESCC.
- •Progressed during or after first line systemic therapy including a doublet of platinum and fluoropyrimidine or paclitaxel with or without anti-PD-1/PD-L1-directed therapy or anti-CTLA-4 and anti-PD-1/PD-L1-directed combination therapy.
- •Consent to provide results from prior PD-L1 IHC assay score by FDA-approved or equivalent PD-L1 IHC diagnostic tests.
- •Consent to provide archival tumor tissue sample (baseline) is required for enrolment.
- •Cohort C (1L Esophageal Squamous Cell Carcinoma [ESCC]) - Specific Inclusion Criteria:
- •Histologically or cytologically documented unresectable, locally advanced or metastatic ESCC.
- •Consent to provide baseline tumor tissue is required.
- •Consent to provide results from prior PD-L1 IHC assay score by FDA-approved or equivalent PD-L1 IHC diagnostic tests.
- •Calculated creatinine clearance ≥60 mL/min.
- •Cohort D, Arms D1 and D2 (4L+ Colorectal Carcinoma [CRC]) - Specific Inclusion Criteria:
- •Histologically and/or cytologically documented unresectable advanced or metastatic colorectal adenocarcinoma. RAS, BRAF, and microsatellite instability/mismatch repair status for each participant must be documented, according to country level guidelines.
- •Participants who have no available therapies with a proven clinical benefit available in the participant's country per investigator. These therapies include the following: fluoropyrimidine, oxaliplatin, irinotecan-based chemotherapy, anti-VEGF biological therapy (eg, bevacizumab, aflibercept, ramucirumab), an anti-EGFR therapy (eg, cetuximab, panitumumab) if RAS wildtype unless right-sided, either trifluridine/tipiracil, fruqintinib or regorafenib, and a BRAF inhibitor (ie, encorafenib) in BRAF V600E mutant).
- •Participants who received oxaliplatin in the adjuvant setting and developed metastatic disease during or within 6 months of completing adjuvant therapy are considered eligible without receiving oxalipatin-based therapy in the metastatic setting.
- •Consent to provide baseline tumor tissue sample is required for enrolment.
排除标准
- •History of prior malignancy other than the cancer under study that is progressing or has required active treatment within the past 3 years.
- •Symptomatic or untreated central nervous system metastases, including leptomeningeal metastases, requiring concurrent treatment, including but not limited to surgery, radiation, and/or corticosteroids.
- •Major surgery requiring general anesthesia within 28 days prior to the first dose of study treatment, still recovering from prior surgery, or with surgery scheduled during the study.
- •Prior exposure to anti-C-C motif chemokine receptor 8 (CCR8) antibody.
- •History of Grade 4 allergic or anaphylactic reaction to any monoclonal antibody (mAb) therapy or any excipient in the study treatment.
- •Active uncontrolled bacterial, fungal, or viral infection including hepatitis B virus (HBV), hepatitis C virus (HCV), known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.
- •Any condition that, in the opinion of the Investigator or Sponsor, would interfere with the interpretation of study results.
- •Cohort A (2L Gastric, Gastro-esophageal-junction [GEJ], Esophageal Adenocarcinoma [EAC]) Specific Exclusion Criteria:
- •Received ≥ 2 prior systemic anticancer therapies for advanced or metastatic disease.
- •Participants at high risk for developing esophageal fistula by clinical assessment or imaging, such as prior history or associated symptoms of esophageal fistula or T4 classification assessed by endoscopic ultrasound (EUS).
- •Cohort B (2L Esophageal Squamous Cell Carcinoma [ESCC]) - Specific Exclusion Criteria:
- •Received ≥ 2 prior systemic anticancer therapies for advanced or metastatic disease.
- •Participants at high risk for developing esophageal fistula by clinical assessment or imaging, such as prior history or associated symptoms of esophageal fistula or T4 classification assessed by endoscopic ultrasound (EUS).
- •Cohort C (1L Esophageal Squamous Cell Carcinoma [ESCC]) - Specific Exclusion Criteria:
- •Received ≥ 1 prior systemic anticancer therapies for advanced or metastatic disease.
- •Participants who progressed during or within 6 months following the last dose of neoadjuvant, or perioperative therapy with curative intent.
- •Participants at high risk for developing esophageal fistula by clinical assessment or imaging, such as prior history or associated symptoms of esophageal fistula or T4 classification assessed by endoscopic ultrasound (EUS).
- •Known dihydropyrimidine dehydrogenase deficiency or thymidine synthase gene polymorphism predisposing the participant to 5-FU toxicity.
- •Known allergies to 5-FU or cisplatin.
- •Note: Other protocol-specified inclusion/exclusion criteria apply.
研究组 & 干预措施
Cohort B - Arm B1: CHS-114 Dose A + Toripalimab
Participants will be treated with dose A of CHS-114 administered as an IV infusion in combination with toripalimab Q3W.
干预措施: CHS-114 (Drug)
Experimental: Cohort D - Arm D2 (Non-Liver Mets): CHS-114 + Toripalimab
Participants will be treated with CHS-114 administered as an IV infusion in combination with toripalimab Q3W.
干预措施: Toripalimab (Drug)
Cohort A - Arm A2: CHS-114 Dose B + Toripalimab
Participants will be treated with dose B of CHS-114 administered as an IV infusion in combination with toripalimab Q3W.
干预措施: CHS-114 (Drug)
Cohort C - Arm C: CHS-114 Dose B + Toripalimab + 5 fluorouracil (5 FU) + Cisplatin
Participants will be treated with dose B of CHS-114 administered as an IV infusion in combination with toripalimab, 5 FU, and cisplatin Q3W.
干预措施: Cisplatin (Drug)
Experimental: Cohort D - Arm D2 (Non-Liver Mets): CHS-114 + Toripalimab
Participants will be treated with CHS-114 administered as an IV infusion in combination with toripalimab Q3W.
干预措施: CHS-114 (Drug)
Cohort A - Arm A1: CHS-114 Dose A + Toripalimab
Participants will be treated with dose A of CHS-114 administered as an intravenous (IV) infusion in combination with toripalimab every 3 weeks (Q3W).
干预措施: CHS-114 (Drug)
Experimental: Cohort D - Arm D1 (Liver Mets): CHS-114 + Toripalimab
Participants will be treated with CHS-114 administered as an IV infusion in combination with toripalimab Q3W.
干预措施: Toripalimab (Drug)
Cohort B - Arm B1: CHS-114 Dose A + Toripalimab
Participants will be treated with dose A of CHS-114 administered as an IV infusion in combination with toripalimab Q3W.
干预措施: Toripalimab (Drug)
Cohort C - Arm C: CHS-114 Dose B + Toripalimab + 5 fluorouracil (5 FU) + Cisplatin
Participants will be treated with dose B of CHS-114 administered as an IV infusion in combination with toripalimab, 5 FU, and cisplatin Q3W.
干预措施: Toripalimab (Drug)
Cohort C - Arm C: CHS-114 Dose B + Toripalimab + 5 fluorouracil (5 FU) + Cisplatin
Participants will be treated with dose B of CHS-114 administered as an IV infusion in combination with toripalimab, 5 FU, and cisplatin Q3W.
干预措施: 5 Fluorouracil (Drug)
Cohort A - Arm A2: CHS-114 Dose B + Toripalimab
Participants will be treated with dose B of CHS-114 administered as an IV infusion in combination with toripalimab Q3W.
干预措施: Toripalimab (Drug)
Cohort B - Arm B2: CHS-114 Dose B + Toripalimab
Participants will be treated with dose B of CHS-114 administered as an IV infusion in combination with toripalimab Q3W.
干预措施: Toripalimab (Drug)
Cohort C - Arm C: CHS-114 Dose B + Toripalimab + 5 fluorouracil (5 FU) + Cisplatin
Participants will be treated with dose B of CHS-114 administered as an IV infusion in combination with toripalimab, 5 FU, and cisplatin Q3W.
干预措施: CHS-114 (Drug)
Experimental: Cohort D - Arm D1 (Liver Mets): CHS-114 + Toripalimab
Participants will be treated with CHS-114 administered as an IV infusion in combination with toripalimab Q3W.
干预措施: CHS-114 (Drug)
Cohort A - Arm A1: CHS-114 Dose A + Toripalimab
Participants will be treated with dose A of CHS-114 administered as an intravenous (IV) infusion in combination with toripalimab every 3 weeks (Q3W).
干预措施: Toripalimab (Drug)
Cohort B - Arm B2: CHS-114 Dose B + Toripalimab
Participants will be treated with dose B of CHS-114 administered as an IV infusion in combination with toripalimab Q3W.
干预措施: CHS-114 (Drug)
结局指标
主要结局
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
时间窗: From first dose of study drug until 90 days after the last dose of study drug (up to approximately 2.25 years)
次要结局
- Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Investigator Assessment(Up to approximately 2.25 years)
- Duration of Response (DOR) Per RECIST v1.1 Based on Investigator Assessment(Up to approximately 2.25 years)
- Disease Control Rate (DCR) Per RECIST v1.1 Based on Investigator Assessment(Up to approximately 2.25 years)
- Progression-free Survival (PFS) Per RECIST v1.1 Based on Investigator Assessment(Up to approximately 2.25 years)
- Landmark PFS Rates(Months 6, 9, and 12)
- Maximum Observed Serum Concentration (Cmax) of CHS-114(Up to approximately 2.25 years (pre-infusion and up to 336 hours post-infusion))
- Time to Reach Cmax (Tmax) of CHS-114(Up to approximately 2.25 years (pre-infusion and up to 336 hours post-infusion))
- Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of CHS-114(Up to approximately 2.25 years (pre-infusion and up to 336 hours post-infusion))
- Number of Participants With Anti-drug Antibodies (ADAs)(Up to approximately 2.25 years)