A Phase 3 study of belrestotug plus dostarlimab compared with placebo plus pembrolizumab in previously untreated PD L1 high NSCLC
- Conditions
- ung Cancer, Non-Small CellTherapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2023-504753-12-00
- Lead Sponsor
- Glaxosmithkline Research & Development Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 796
Is capable of giving signed informed consent as described in Appendix 6 ( Protocol Section 10.6.3), which includes compliance with the requirements and restrictions listed in the ICF and in this protocol., 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, and 1 of the following conditions applies: oIs a WONCBP as defined in Protocol Appendix 1. Or oIs a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), as described in Appendix 1, during the Intervention Period and for at least 4 months after the last dose of study intervention. Female participant agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this timeframe. The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated) in relationship to the first dose of study intervention. oA WOCBP must not be pregnant; this will generally be confirmed via a negative highly sensitive serum pregnancy test within 7 days before the first dose of study intervention. In rare cases where it is suspected that hCG is elevated in the absence of pregnancy (e.g., due to a tumor producing hCG), an ultrasound must be performed to rule out pregnancy. •Additional requirements for pregnancy testing during and after study intervention administration are located in Section 8.3.8. •The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk of inclusion of a woman with an early undetected pregnancy., Is, at the time of signing the ICF, at least 18 years old or the legal age of consent in the jurisdiction in which the study is taking place., Has a histologically or cytologically confirmed diagnosis of 1 of the following: a.Locally advanced, unresectable NSCLC (not eligible for curative surgery and/or definitive radiotherapy with or without chemotherapy), or b.Metastatic NSCLC. NOTE: Squamous or nonsquamous histology is permitted. Mixed tumors will be categorized by the predominant cell type; if small cell or neuroendocrine elements are present, the participant is ineligible., Has not received prior systemic therapy for their locally advanced or metastatic NSCLC. NOTE: Completion of treatment with cytotoxic chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy is allowed if therapy was completed at least 6 months prior to the diagnosis of locally advanced or metastatic disease. Prior treatment with neoadjuvant/adjuvant immunotherapy for resectable disease is permitted if at least 12 months have passed since the last dose of immunotherapy prior to the diagnosis of locally advanced or metastatic disease and no permanent discontinuation of prior immunotherapy treatment due to toxicity., Provides a tumor tissue sample obtained at the time of or after the initial diagnosis of locally advanced or metastatic NSCLC. Although a fresh tumor tissue sample obtained during screening is preferred, an archival tumor specimen (collected within 2 years prior to screening*) is acceptable. Tumor tissue must be from a site not previously irradiated. Biopsies obtained prior to the administration of any systemic ther
1.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. b.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. Participants with nonsquamous histology and unknown or indeterminate ALK status are excluded. c.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 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. A participant who is clinically stable following treatment of these conditions (including therapeutic thoracocentesis, paracentesis, or pericardiocentesis) is eligible if the participant otherwise meets entry criteria., 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. b.Cardiomyopathy, myocarditis, myocardial infarction, acute coronary syndromes (including angina pectoris), coronary angioplasty, stenting, or bypass grafting. c.Congestive heart failure (Class III or IV) as defined by the New York Heart Association functional classification system (Appendix 8) [NYHA, 1994]. d.Symptomatic pericarditis. NOTE: Participants with troponin and/or NT-proBNP/BNP values =2x ULN will require review by a cardiologist or locally appropriate specialist to identify underlying conditions that may meet exclusion criteria or that may require increased monitoring during study participation. In addition, cardiologist or locally appropriate specialist review should be considered for potentially significant ECG abnormalities such as AV block (except for first degree), new cardiac arrhythmias, or frequent PVCs. The sponsor is to be informed regarding these participants., 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. NOTE: Stable ch
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method