Phase II Dose Optimization Study of Platinum/Etoposide Plus Ivonescimab (CEI) as First-Line Treatment of Extensive-Stage Small Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- PrECOG, LLC.
- 入组人数
- 60
- 试验地点
- 13
- 主要终点
- Optimal Dose of Ivonescimab in Combination with Carboplatin and Etoposide - Overall Response Rate (ORR)
研究概览
简要总结
Eligible untreated participants with Extensive Stage Small Cell Lung Cancer (ES-SCLC) who are ≥ 18 years of age will be randomized to receive ivonescimab 10 milligrams per kilogram (mg/kg) or ivonescimab 20 mg/kg in combination with carboplatin and etoposide.
Ivonescimab is a type of drug called a bispecific antibody. Antibodies are proteins that specifically recognize and bind to other types of proteins called antigens. Antibodies and antigens can work together to help the immune system fight cancer cells. Bispecific antibody, meaning it targets two different molecules at the same time.
Ivonescimab is a new drug that may help the immune system attack cancer cells and may also block certain pathways that cancer uses to grow and spread. This dual action of ivonescimab aims to help the immune system to fight the cancer and also disrupt tumor growth by blocking blood vessel formation that tumors use to grow.
Participants will receive induction with 4 cycles of ivonescimab (dose determined by randomization) with standard of care carboplatin and etoposide followed by maintenance therapy with ivonescimab at the same dose received during induction. Treatment will continue until disease progression, unacceptable toxicity or participant withdrawal.
The purpose of this study is to determine what dose of ivonescimab works best in combination with carboplatin and etoposide chemotherapy in ES-SCLC. We will also examine the side effects, good and bad, associated with ivonescimab.
详细描述
Randomized, Phase II, open-label trial designed to determine the optimal dose of ivonescimab with carboplatin and etoposide for a more diverse Western participant population with ES- SCLC based on overall response rate and safety profile of two dose levels of ivonescimab (10 mg/kg versus 20 mg/kg) previously evaluated in the Chinese population.
The simultaneous blockade of vascular endothelial growth factor (VEGF) and Programmed Death-Ligand 1 (PDL-1) by ivonescimab may achieve a higher target binding of VEGF and PD-1 within the tumor microenvironment and produce increased anti-tumor effect with an improved safety profile than administration of anti-PD-(L)1 and anti-VEGF therapies separately.
Participants will be randomized 1:1 to receive ivonescimab 10 mg/kg or 20 mg/kg. Induction treatment will be administered on a 21-day cycle for four cycles with standard of care carboplatin and etoposide.
Following the induction phase, participants will continue maintenance therapy with ivonescimab on a 21-day cycle at the dose received during induction (10 mg/kg or 20 mg/kg). Treatment will be discontinued in all participants who have evidence of progressive disease by Response Criteria Evaluation in Solid Tumors version 1.1 (RECIST v1.1).
Research tumor tissue will be requested at baseline for future research. Research blood samples will also be obtained for future research which may include measuring the level of ivonescimab in the blood and immune responses or antibodies to ivonescimab.
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
- •Selection Criteria:
- •Patients must have pathologically confirmed Extensive Stage Small Cell Lung Cancer (ES-SCLC).
- •No prior systemic therapy for the disease under study (ES-SCLC).
- •Patients must have measurable disease according to Response Evaluation Criteria for Solid Tumors (RECIST) v1.
- •Patient must be ≥ 18 years of age.
- •Patient must have an ECOG performance status of 0-
- •Patient must have the ability to understand and willingness to sign a written informed consent document.
- •Willing to provide archived tumor tissue (if sufficient tumor tissue available) and blood samples for research.
- •Patient must have adequate organ function and marrow function as defined below, obtained ≤ 14 days prior to registration/randomization. No blood transfusions or growth factor therapy allowed within 7 days of screening labs.
- •Absolute Neutrophil Count (ANC) ≥ 1500/microliter (mcL)
- •Platelets ˃100,000/mcL
- •Hemoglobin >9.0 gram/deciliter (g/dL)
- •Prothrombin time (PT) or international normalized ratio (INR) ≤ 1.5x Upper Limit Normal (ULN), and partial prothrombin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5x ULN
- •Serum Creatinine ≤ 2x ULN
- •Creatinine clearance (CrCl) ≥ 50 milliliter/minute (mL/min)
- •Urine Protein <2+
- •Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤ 2.5x ULN or ≤ 5x ULN for patients with liver metastasis
- •Total Bilirubin ≤ 1.5x ULN or ≤ 3x ULN for patients with liver metastasis or suspected/documented Gilbert's disease
- •Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used.
- •Patient must not expect to conceive or father children by using an accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study, and for 120 days after the last dose of study drug(s).
- •Patients must not have symptomatic central nervous system (CNS) metastases, CNS metastasis ≥ 1.5 cm, CNS radiation within 7 days prior to randomization, potential need for CNS radiation within the first cycle, or leptomeningeal disease.
- •Patients must not have imaging during the screening period that shows:
- •Radiologically documented evidence of major blood vessel invasion (central pulmonary artery, central pulmonary veins, aorta, brachiocephalic artery, common carotid artery, subclavian artery, superior vena cava) or tumor invading organs (heart, trachea, esophagus, central bronchi [not including segmental bronchi]) or if there is a risk of esophagotracheal or esophagopleural fistula .
- •Radiographic evidence of major blood vessel encasement with narrowing of the vessel or intratumor lung cavitation or necrosis that the investigator determines will pose a significantly increased risk of bleeding.
- •Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
- •Patients must not have major surgical procedures or serious trauma within 28 days prior to randomization or plans for major surgical procedures within 28 days after the first dose.
- •Patients must not have history of bleeding tendencies or coagulopathy and/or clinically significant bleeding symptoms or risk within 4 weeks prior to randomization, including but not limited to:
- •Hemoptysis (defined as coughing up ≥ 0.5 teaspoon of fresh blood or small blood clots). Transient hemoptysis associated with diagnostic bronchoscopy is allowed.
- •Nasal bleeding/epistaxis (bloody nasal discharge is allowed).
- •Current use of prophylactic or full-dose anticoagulants or anti-platelet agents for therapeutic purposes that is not stable prior to randomization is not allowed.
- •Patients must not have history of major diseases before randomization, specifically:
- •Unstable angina, myocardial infarction, congestive heart failure (New York Heart Association (NYHA) classification ≥ Grade 2) or unstable vascular disease (e.g., aortic aneurysm at risk of rupture, Moyamoya disease) that required hospitalization within 12 months prior to randomization, or other cardiac impairment that may affect the safety evaluation of the study drug (e.g., poorly controlled arrhythmias, myocardial ischemia).
- •History of any grade arterial thromboembolic event, Grade 3 and above venous thromboembolic event, as specified in National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 5.0, transient ischemic attack, cerebrovascular accident, hypertensive crisis, or hypertensive encephalopathy within 12 months prior to randomization.
- •History of esophageal gastric varices, severe ulcers, wounds that do not heal, abdominal fistula, intra-abdominal abscesses, or acute gastrointestinal bleeding within 6 months prior to randomization.
- •History of perforation of the gastrointestinal tract and/or fistula, history of gastrointestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), extensive bowel resection (partial colectomy or extensive small bowel resection) within 6 months prior to randomization.
- •Patients must not have poorly controlled hypertension with repeated systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg after oral antihypertensive therapy.
- •Patients must not have prolongation of QTc interval >480 msec
- •Patients must not have active autoimmune or lung disease requiring systemic therapy (e.g., with disease modifying drugs, prednisone >10 mg daily or equivalent, immunosuppressant therapy) within 2 years prior to randomization.
- •Patients must not have severe infection within 4 weeks prior to randomization, including but not limited to comorbidities requiring hospitalization, sepsis, or severe pneumonia; active infection requiring systemic anti-infective therapy within 2 weeks prior to randomization (excluding antiviral therapy for hepatitis B or C).
- •Patients must not have uncontrolled pleural effusions, pericardial effusions, or ascites that is clinically symptomatic.
- •Patients must not have history of non-infectious pneumonia requiring systemic corticosteroids, or current interstitial lung disease.
- •Patients must not have active or prior history of inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis, or chronic diarrhea.
- •Patients must not have pre-existing peripheral neuropathy ≥ Grade 2 by CTCAE V5.
- •Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration/randomization are eligible for this trial.
- •Patient must not have received any live vaccine within 28 days prior to registration/randomization.
- •Patients with a known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent are not eligible.
- •Patients with any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of the treatment according to the protocol are not eligible.
- •Patients may not participate in any other therapeutic clinical trials, including those with other investigational agents not included in this trial during treatment on this study without prior approval from PrECOG.
排除标准
- 未提供
研究组 & 干预措施
Arm A: Ivonescimab 10 mg/kg
Induction with ivonescimab 10 mg/kg, carboplatin and etoposide every 21 days x 4 cycles followed by maintenance ivonescimab 10 mg/kg every 21 days until progression, unacceptable toxicity or participant withdrawal. Up to 24 months of ivonescimab from cycle 1 day 1 of Induction.
干预措施: Ivonescimab 10 mg/kg (Drug)
Arm B: Ivonescimab 20 mg/kg
Induction with ivonescimab 20 mg/kg, carboplatin and etoposide every 21 days x 4 cycles followed by maintenance ivonescimab 20 mg/kg every 21 days until progression, unacceptable toxicity or participant withdrawal. Up to 24 months of ivonescimab from cycle 1 day 1 of Induction.
干预措施: Ivonescimab 20 mg/kg (Drug)
结局指标
主要结局
Optimal Dose of Ivonescimab in Combination with Carboplatin and Etoposide - Overall Response Rate (ORR)
时间窗: 18 months
Overall Response Rate (ORR) defined as the proportion of participants achieving complete response (CR) or partial response (PR) as best response on treatment based on RECIST v1.1 criteria at each dose level.
Optimal Dose of Ivonescimab in Combination with Carboplatin and Etoposide - Grade 3-5 Treatment-Related Toxicity Rate
时间窗: 18 months
All grade 3-5 adverse events (AE) with treatment attribution of possibly, probably or definite based on Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE V5.0) that are not resolved in accordance with treatment guidelines will be counted. Rate is the proportion of treated participants experiencing at least one of these adverse events as defined during the time of observation.
次要结局
- Overall Survival (OS) of of Ivonescimab in Combination with Carboplatin and Etoposide(24 months)
- Progression-Free Survival (PFS) of Ivonescimab in Combination with Carboplatin and Etoposide(18 months)
- Disease Control Rate (DCR) of Ivonescimab in Combination with Carboplatin and Etoposide(18 months)
- Duration of Response (DoR) of Ivonescimab in Combination with Carboplatin and Etoposide(18 months)
- Duration of Stable Disease of Ivonescimab in Combination with Carboplatin and Etoposide(18 months)