CTRI/2024/10/075244招募中3 期
A randomized, multicenter, double-blind, Phase 3 study to investigate the safety and efficacy of belrestotug in combination with dostarlimab compared with placebo in combination with pembrolizumab in participants with previously untreated, unresectable, locally advanced or metastatic PD-L1 selected non small cell lung cancer (GALAXIES LUNG 301)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 1,000
- 试验地点
- 13
- 主要终点
- Progression-free survival per RECIST 1.1 by Blinded independent central review
研究概览
简要总结
Purpose
The purpose of this Phase 3 study is to evaluate the efficacy, safety, PK, and pharmacodynamics of dostarlimab plus belrestotug compared with pembrolizumab plus placebo in participants with previously untreated, unresectable, locally advanced or metastatic PD-L1-high NSCLC.
Hypothesis
This Phase 3 study design is based on the hypothesis that a combination of the anti-PD-1 mAb dostarlimab with the anti-TIGIT mAb belrestotug compared with standard of care (pembrolizumab) will lead to a meaningful improvement in PFS and OS for participants with previously untreated, unresectable, locally advanced or metastatic NSCLC with a high PD-L1 expression (TC ≥50%).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 95.00 Year(s)（—）
- 性别
- All
入选标准
- •Participants are eligible to be included in the study only if all of the following criteria apply 2)Is capable of giving signed informed consent having age atleast 18 or the legal age of consent in the jurisdiction in which the study is taking place 3)ALocally advanced, unresectable NSCLC (not eligible for curative surgery and/or definitive radiotherapy with or without chemotherapy), or Metastatic NSCLC.
- •Has not received prior systemic therapy.
- •Has a PD-L1-high (TC 50%) tumor as determined by the VENTANA PD-L1(SP263) CDx Assay at a central laboratory.
- •Has an ECOG PS score of 0 or 1 and adequate organ function.
- •If of childbearing potential, female participants must be willing to use contraception.
- •Contraceptive use by female participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- •A female participant is eligible to participate if she is not pregnant or breastfeeding.
排除标准
- •Participants are excluded from the study if any of the following criteria apply-
- •Has NSCLC with a tumor that harbors any of the following molecular alterations: a.
- •EGFR mutations that are sensitive to available targeted inhibitor therapy (including, but not limited to, deletions in exon 19, exon 20 insertion mutation, and exon 21 [L858R] substitution mutation).
- •All participants with nonsquamous histology must have been tested for EGFR mutation status using a tissue-based test; use of an approved test is strongly encouraged.
- •Participants with squamous histology do not need to be tested for EGFR mutation status.
- •Participants with nonsquamous histology and unknown or indeterminate EGFR status are excluded.
- •ALK translocations that are sensitive to available targeted inhibitor therapy.
- •All participants with nonsquamous histology must have been tested for ALK fusion mutation status using a tissue-based test; use of an approved test is strongly encouraged.
- •Participants with squamous histology do not need to be tested for ALK fusion mutation status.
- •Any other known genomic aberrations or oncogenic driver mutations for which a locally approved targeted therapy is available for first-line treatment of locally advanced or metastatic NSCLC.
- •Has had surgery within 4 weeks of the first dose of study intervention and has not recovered from AEs (i.e., has any ongoing surgery-related events equal to or more than than grade 1) 3) Has received prior therapy with any immune-checkpoint inhibitors, including antibodies or drugs targeting PD-(L)1, CTLA-4, TIGIT, or other checkpoint pathways 4) Has never smoked, defined as smoking less than 100 tobacco cigarettes in a lifetime 5) Has an invasive malignancy or history of invasive malignancy other than the disease under study within the last 5 years,except as noted below: a.
- •Participants may be enrolled in the study with a history of any other invasive malignancy for which the participant was definitively treated, from which the participant has been disease-free for at least 2 years, and which, in the opinion of the principal investigator and medical monitor, is not expected to affect the evaluation of the effects of the study intervention on the currently targeted malignancy.
- •Participants with curatively treated basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, in situ cervical cancer, and/or in situ breast cancer may be enrolled in the study.
- •Has either of the following: a.
- •Known symptomatic, untreated, or actively progressing brain metastases.
- •Any leptomeningeal disease (regardless of symptomatology, treatment status, or stability).
- •Has autoimmune disease or syndrome (current or history thereof) that required systemic treatment within the past 2 years.
- •Replacement therapies (e.g., insulin, thyroxine, or physiologic doses of corticosteroids for treatment of adrenal or pituitary insufficiency) are not considered systemic treatments and are allowed.
- •Replacement therapy is not considered a form of systemic therapy.
- •Corticosteroid use is allowed as premedication for hypersensitivity reactions (e.g., IV contrast allergies/reactions).
- •Use of topical, inhaled, or intranasal corticosteroids, local steroid injection, or steroid eye drops is allowed.
- •Daily prednisone at doses of ≤10 mg is an example of replacement therapy and are permitted in this study.
- •Equivalent hydrocortisone doses are also permitted if administered as a replacement therapy.
- •Has received any live vaccine within 30 days prior to first dose of study intervention.
- •Has any history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis.
- •Has advanced, symptomatic, or visceral spread and is considered to be at imminent risk of life-threatening complications (including, but not limited to, participants with massive uncontrolled effusions [e.g., pleural, pericardial, peritoneal]).
- •Has symptomatic ascites, pleural effusion, or pericardial effusion.
- •Has active inflammatory bowel disease, acute diverticulitis, intra-abdominal abscess, gastrointestinal obstruction, or peritoneal carcinomatosis.
- •Has a history or evidence of cardiac abnormalities within the 6 months prior to enrollment, including: a.
- •Serious, uncontrolled cardiac arrhythmia or clinically significant ECG abnormalities including second-degree (Type II) or third-degree AV block.
- •Cardiomyopathy, myocarditis, myocardial infarction, acute coronary syndromes (including angina pectoris), coronary angioplasty, stenting, or bypass grafting.
- •Symptomatic pericarditis.
- •Has current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis.
- •Has any infectious diseases described below: a.
- •A severe infection requiring IV antibiotics or requiring hospitalization for infection or complication of infection or severe pneumonia within 4 weeks prior to randomization.
- •Active tuberculosis (i.e., history of exposure or history of positive tuberculosis test, plus presence of clinical symptoms or physical or radiographic findings).
- •Has a known HIV infection 17) Has a history of severe hypersensitivity to mAbs or to any of the excipients in the formulations of the components of the study interventions.
- •Has any serious and/or unstable pre-existing medical (aside from malignancy), psychiatric, or other condition that could, in the opinion of the investigator, interfere with the participant’s safety, obtaining informed consent, or compliance with the study procedures.
- •Is, at the time of signing the ICF, a regular user (including recreational use) of any illicit drugs or has a recent history (within the last year) of substance abuse (including alcohol) that, in the opinion of the investigator, would interfere with the evaluation of the study intervention or interpretation of safety.
- •Is currently participating in or has participated in a study of an investigational therapy within 4 weeks prior to the first dose of study intervention.
- •Has a history of allogeneic tissue/stem cell transplant or solid organ transplant.
结局指标
主要结局
Progression-free survival per RECIST 1.1 by Blinded independent central review
时间窗: Time point - defined as the time from the date of randomization to the date of first documented Progressive disease or death | due to any cause, whichever comes first
Overall survival
时间窗: Time point - defined as the time from the date of randomization to the date of first documented Progressive disease or death | due to any cause, whichever comes first
次要结局
- To Evaluate Efficacy-(Objective response rate - defined as the percentage of participants with a confirmed Complete response or confirmed Partial Response per RECIST 1.1 by investigator assessment)
- To Evaluate Efficacy-(• Molecular response rate, defined as the percentage of participants with a molecular response)
- To Evaluate Efficacy-(Duration of response per RECIST 1.1 by investigator assessment,)
- To Evaluate Efficacy-(Time to first subsequent therapy)
- To Evaluate Safety(• Incidence of Treatment-emergent adverse events, Serious Adverse Events, & Adverse Events of Special Interest)
研究者
Dr Yogesh Mane
GSK Pharma India Private Limited
研究点 (13)
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