An Open-label, Randomized, Phase I/II Trial Investigating the Safety and Efficacy of IO102 in Combination With Pembrolizumab, With or Without Chemotherapy, as First-line Treatment for Patients With Metastatic Non-Small Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- IO Biotech
- 入组人数
- 109
- 试验地点
- 13
- 主要终点
- Phase 1 (safety run-in)
研究概览
简要总结
The purpose of this study is to determine if IO102 combined with pembrolizumab with or without chemotherapy is safe tolerable and effective in the treatment of Non-small Cell Lung Carcinoma (NSCLC).
The hypothesis is that IO102 will improve the objective response rate (ORR) in patients with metastatic NSCLC.
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
- •Histologically or cytologically confirmed metastatic NSCLC or non squamous NSCLC
- •Have biomarker-positive solid tumor
- •Male participants of childbearing potential must agree to use an adequate method of contraception starting with the first dose of study medication through 120 days after the last dose of study medication
- •Female participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication
- •The participant must provide written informed consent
- •Have measurable disease per RECIST 1.1
- •Have provided a blood sample and archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
- •Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1
- •Adequate organ function
排除标准
- •Prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137) and was discontinued from that treatment due to a Grade 3 or higher immune-related AE (irAE)
- •Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
- •Radiotherapy within 2 weeks of start of trial treatment
- •Vaccination with a live vaccine within 30 days prior to the first dose of trial treatment.Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g. FluMist®) are live attenuated vaccines and are not allowed.
- •Is currently participating in or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of trial treatment.
- •Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of trial treatment.
- •Has a known additional malignancy that is progressing or has required active treatment within the past 2 years.
- •Has known active CNS metastases and/or carcinomatous meningitis.
- •Has severe hypersensitivity (≥Grade 3) to IO102, pembrolizumab, carboplatin, pemetrexed and/or any of its excipients.
- •Has an active autoimmune disease that has required systemic treatment in past 2 years.
- •Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
- •Has an active infection requiring systemic therapy.
- •Has a known history of human immunodeficiency virus (HIV) infection.
- •Known active Hepatitis B or Hepatitis C
- •Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator.
- •Has known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the trial.
- •Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial.
研究组 & 干预措施
Cohort A2
Drug: pembrolizumab (Keytruda) 200 mg IV infusion on Day 1 of each 3 week cycle
干预措施: pembrolizumab (Keytruda) (Biological)
Cohort A1
Drug: IO102 100µg administered subcutaneously (SC) on Day 1 of each 3 week cycle PLUS Drug: pembrolizumab (Keytruda) 200 mg intravenous (IV) infusion on Day 1 of each 3 week cycle
干预措施: IO102 (Biological)
Cohort A1
Drug: IO102 100µg administered subcutaneously (SC) on Day 1 of each 3 week cycle PLUS Drug: pembrolizumab (Keytruda) 200 mg intravenous (IV) infusion on Day 1 of each 3 week cycle
干预措施: pembrolizumab (Keytruda) (Biological)
Cohort B1
Drug: IO102 100µg SC on Day 1 of each 3 week cycle PLUS Drug: pembrolizumab (Keytruda) 200 mg IV on Day 1 of each 3 week cycle PLUS Drug: carboplatin (Carboplatin Kabi) at a target AUC of 5 mg/mL IV infusion on Day 1 of each 3 week cycle for a max of 4 administrations PLUS Drug: pemetrexed (Pemetrexed Alvogen) at 500 mg/m2 IV infusion on Day 1 of each 3 week cycle
干预措施: IO102 (Biological)
Cohort B1
Drug: IO102 100µg SC on Day 1 of each 3 week cycle PLUS Drug: pembrolizumab (Keytruda) 200 mg IV on Day 1 of each 3 week cycle PLUS Drug: carboplatin (Carboplatin Kabi) at a target AUC of 5 mg/mL IV infusion on Day 1 of each 3 week cycle for a max of 4 administrations PLUS Drug: pemetrexed (Pemetrexed Alvogen) at 500 mg/m2 IV infusion on Day 1 of each 3 week cycle
干预措施: pembrolizumab (Keytruda) (Biological)
Cohort B1
Drug: IO102 100µg SC on Day 1 of each 3 week cycle PLUS Drug: pembrolizumab (Keytruda) 200 mg IV on Day 1 of each 3 week cycle PLUS Drug: carboplatin (Carboplatin Kabi) at a target AUC of 5 mg/mL IV infusion on Day 1 of each 3 week cycle for a max of 4 administrations PLUS Drug: pemetrexed (Pemetrexed Alvogen) at 500 mg/m2 IV infusion on Day 1 of each 3 week cycle
干预措施: Carboplatin (Carboplatin Kabi) (Drug)
Cohort B1
Drug: IO102 100µg SC on Day 1 of each 3 week cycle PLUS Drug: pembrolizumab (Keytruda) 200 mg IV on Day 1 of each 3 week cycle PLUS Drug: carboplatin (Carboplatin Kabi) at a target AUC of 5 mg/mL IV infusion on Day 1 of each 3 week cycle for a max of 4 administrations PLUS Drug: pemetrexed (Pemetrexed Alvogen) at 500 mg/m2 IV infusion on Day 1 of each 3 week cycle
干预措施: Pemetrexed (Pemetrexed Alvogen) (Drug)
Cohort B2
Drug: pembrolizumab (Keytruda) 200 mg IV on Day 1 of each 3 week cycle PLUS Drug: carboplatin (Carboplatin Kabi) at a target AUC of 5 mg/mL IV infusion on Day 1 of each 3 week cycle for a max of 4 administrations PLUS Drug: pemetrexed (Pemetrexed Alvogen) at 500 mg/m2 IV infusion on Day 1 of each 3 week cycle
干预措施: pembrolizumab (Keytruda) (Biological)
Cohort B2
Drug: pembrolizumab (Keytruda) 200 mg IV on Day 1 of each 3 week cycle PLUS Drug: carboplatin (Carboplatin Kabi) at a target AUC of 5 mg/mL IV infusion on Day 1 of each 3 week cycle for a max of 4 administrations PLUS Drug: pemetrexed (Pemetrexed Alvogen) at 500 mg/m2 IV infusion on Day 1 of each 3 week cycle
干预措施: Carboplatin (Carboplatin Kabi) (Drug)
Cohort B2
Drug: pembrolizumab (Keytruda) 200 mg IV on Day 1 of each 3 week cycle PLUS Drug: carboplatin (Carboplatin Kabi) at a target AUC of 5 mg/mL IV infusion on Day 1 of each 3 week cycle for a max of 4 administrations PLUS Drug: pemetrexed (Pemetrexed Alvogen) at 500 mg/m2 IV infusion on Day 1 of each 3 week cycle
干预措施: Pemetrexed (Pemetrexed Alvogen) (Drug)
结局指标
主要结局
Phase 1 (safety run-in)
时间窗: One cycle i.e. 3 weeks
Dose Limiting Toxicity graded per Common Terminology Criteria for Adverse Events (CTCAE) version 4.03
Phase 2 (efficacy)
时间窗: From date of randomization until date of death from any cause, withdrawal of consent or loss to follow up whichever came first, assessed for up to 35 cycles (2 years)
Objective Response Rate (ORR) evaluated by RECIST 1.1 and defined as the rate of complete response (CR) + partial response (PR)
次要结局
- ORR(From date of randomization until date of death from any cause, withdrawal of consent or loss to follow up whichever came first, assessed for up to 35 cycles (2 years))