A Phase I/II, Dose-Escalation and Dose-Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Antitumor Activities of CS2009, a Tri-specific Antibody Targeting PD-1/VEGFA/CTLA-4, as Monotherapy and Combination Therapy in Participants With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 800
- 试验地点
- 41
- 主要终点
- [Dose Escalation] Maximum tolerated dose (MTD) of CS2009
研究概览
简要总结
This is a first-in-human (FIH), open-label, and multi-center Phase I/II study designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of CS2009 as Monotherapy and Combination Therapy in Participants with Advanced Solid Tumors. The study is comprised of a Phase I dose escalation and Phase II dose expansion.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Evidence of a personally signed and dated informed consent document.
- •Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
- •Age ≥ 18 years on the day of signing informed consent.
- •Pathologically or cytologically confirmed, unresectable advanced solid tumors, including but not limited to non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), gastric cancer (GC), ovarian cancer (OC), cervical cancer (CC), etc.
- •Failure of established standard of care for advanced disease, or no available standard of care.
- •Pathologically or cytologically confirmed unresectable advanced solid tumors, including non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), etc.
- •Participants with at least one measurable lesion as defined per RECIST v1.1 solid tumor.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Adequate organ function.
- •Fertile male participants and female participants of childbearing potential must be willing to use an effective method of birth control from providing signed consent and for 180 days after the last investigational product administration.
- •Female participants of childbearing potential must have a negative pregnancy test ≤ 7 days prior to the first dose of the investigational product.
排除标准
- •History of a second malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured.
- •Known primary central nervous system (CNS) tumor or solid tumor CNS metastasis that is either symptomatic, untreated, or requires therapy.
- •Presence of uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage within 4 weeks prior to the first dose of investigational product.
- •Receipt of systemic corticosteroid treatment or any other form of immune suppressing treatment within 7 days prior to the first dose of investigational product.
- •Active or prior history of definite inflammatory bowel disease.
- •History of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, or presence of active or suspected ILD/pneumonitis.
- •Active infections requiring systemic therapy within 2 weeks prior to the first dose of investigational product.
- •Positive for human immunodeficiency virus (HIV) or presence of acquired immune deficiency syndrome (AIDS).
- •Active Hepatitis B or C infection.
- •Active pulmonary tuberculosis (TB).
- •Major surgery, chemotherapy, definitive radiotherapy, target therapy, immunotherapy, or other anti-cancer therapy within 21 days prior to the first dose of investigational product.
- •Palliative radiotherapy within 14 days prior to the first dose of investigational product, or receipt of radioactive drug within 56 days prior to the first dose of investigational product.
- •Administration of live vaccine within 28 days prior to the first dose of investigational product.
- •History of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.
- •Receipt of antitumor Chinese herbal preparations or Chinese patent medicine within 7 days prior to the first dose of investigational product.
- •Receipt of any other investigational drugs within 21 days prior to the first dose in this trial.
- •History of hypersensitivity or idiosyncrasy to the excipients of the study drug or any monoclonal antibody.
- •Any toxic effects of prior therapy or surgical procedures unresolved to baseline severity or NCI-CTCAE Version 5.0 Grade ≤
- •Active alcohol or drug abuse.
- •Female participants who are pregnant or breastfeeding.
- •Other acute or chronic medical or psychiatric conditions that may increase the risk associated with study participation or investigational product administration.
研究组 & 干预措施
Dose Expansion
Participants will be administered the recommended dose(s) of CS2009 with or without chemotherapy according to dose-escalation data.
干预措施: Gemcitabine (Drug)
Dose Expansion
Participants will be administered the recommended dose(s) of CS2009 with or without chemotherapy according to dose-escalation data.
干预措施: Paclitaxel (Drug)
Dose Expansion
Participants will be administered the recommended dose(s) of CS2009 with or without chemotherapy according to dose-escalation data.
干预措施: Etoposide (Drug)
Dose Escalation
Participants will be administered escalating doses of CS2009.
干预措施: CS2009 (Drug)
Dose Expansion
Participants will be administered the recommended dose(s) of CS2009 with or without chemotherapy according to dose-escalation data.
干预措施: CS2009 (Drug)
Dose Expansion
Participants will be administered the recommended dose(s) of CS2009 with or without chemotherapy according to dose-escalation data.
干预措施: Carboplatin (Drug)
Dose Expansion
Participants will be administered the recommended dose(s) of CS2009 with or without chemotherapy according to dose-escalation data.
干预措施: Pemetrexed (Drug)
Dose Expansion
Participants will be administered the recommended dose(s) of CS2009 with or without chemotherapy according to dose-escalation data.
干预措施: Capecitabine (Drug)
Dose Expansion
Participants will be administered the recommended dose(s) of CS2009 with or without chemotherapy according to dose-escalation data.
干预措施: Nab-paclitaxel (Drug)
Dose Expansion
Participants will be administered the recommended dose(s) of CS2009 with or without chemotherapy according to dose-escalation data.
干预措施: Oxaliplatin (Drug)
Dose Expansion
Participants will be administered the recommended dose(s) of CS2009 with or without chemotherapy according to dose-escalation data.
干预措施: Irinotecan (Drug)
Dose Expansion
Participants will be administered the recommended dose(s) of CS2009 with or without chemotherapy according to dose-escalation data.
干预措施: 5-FU (Drug)
Dose Expansion
Participants will be administered the recommended dose(s) of CS2009 with or without chemotherapy according to dose-escalation data.
干预措施: Cisplatin (Drug)
Dose Expansion
Participants will be administered the recommended dose(s) of CS2009 with or without chemotherapy according to dose-escalation data.
干预措施: Docetaxel (Drug)
Dose Expansion
Participants will be administered the recommended dose(s) of CS2009 with or without chemotherapy according to dose-escalation data.
干预措施: Leucovorin (Drug)
结局指标
主要结局
[Dose Escalation] Maximum tolerated dose (MTD) of CS2009
时间窗: Cycle 1 (Up to 21 Days)
Participants will receive CS2009 via intravenous (IV) infusion on Day 1 of repeated 21-day cycles (Q3W). The MTD will be determined, if any, by the number of participants who experience a dose limiting toxicity (DLT).
[Dose Escalation] Tentative recommended Phase II dose (RP2D) of CS2009
时间窗: Cycle 1 (Up to 21 Days)
The selection of tentative RP2D will be based on consideration of overall safety information together with available pharmacokinetic, pharmacodynamic, and efficacy data. The tentative RP2D may be the MTD or a lower dose within the tolerable dose range.
[Dose Escalation] Number of participants with adverse events (AEs)
时间窗: Up to approximately 2 years
[Dose Expansion] Objective response rate (ORR) evaluated by investigators per RECIST v1.1
时间窗: Up to approximately 2 years
次要结局
- [Dose Escalation & Expansion] Area under the curve (AUC) of CS2009(Up to approximately 2 years)
- [Dose Escalation & Expansion] Maximum concentration (Cmax) of CS2009(Up to approximately 2 years)
- [Dose Escalation & Expansion] Elimination half-life (t1/2) of CS2009(Up to approximately 2 years)
- [Dose Escalation & Expansion] Minimum concentration (Cmin) of CS2009(Up to approximately 2 years)
- [Dose Escalation & Expansion] Number of participants with anti-CS2009 antibodies(Up to approximately 2 years)
- [Dose Escalation] Objective response rate (ORR) evaluated by investigators per RECIST v1.1(Up to approximately 2 years)
- [Dose Expansion] Number of participants with adverse events (AEs)(Up to approximately 2 years)