A Phase 3 Study of Pembrolizumab (MK-3475) in Combination with Concurrent Chemoradiation Therapy Followed by Pembrolizumab with or without Olaparib vs Concurrent Chemoradiation Therapy Followed by Durvalumab in Participants with Unresectable, Locally Advanced, Stage III Non-Small Cell Lung Cancer (NSCLC)

Merck Sharp & Dohme LLC0 个研究点目标入组 870 人开始时间: 2020年3月2日最近更新: 2023年1月9日

适应症

试验速览

阶段: 1 期
状态: 进行中（未招募）
发起方: Merck Sharp & Dohme LLC
入组人数: 870

研究概览入排标准研究者记录与标识符相似试验

研究概览

简要总结

暂无简介。

研究设计

研究类型: Interventional clinical trial of medicinal product

入排标准

性别: All

入选标准

•1. Has pathologically (histologically or cytologically) confirmed diagnosis of NSCLC.
•2. Has Stage IIIA, IIIB, or IIIC NSCLC by American Joint Committee on Cancer Version 8.
•3. Is unable to undergo surgery with curative intent for Stage III NSCLC as documented by a multidisciplinary tumor board or by the treating physician in consultation with a thoracic surgeon.
•4. Has no evidence of metastatic disease, indicating Stage IV NSCLC, in whole-body fluorodeoxyglucose (FDG)-PET or FDG-PET/CT and CT or MRI scans of diagnostic quality of chest, abdomen, pelvis and brain.
•5. Has measurable disease as defined by RECIST 1.1, with at least one lesion being appropriate for selection as a target lesion, as determined by local site investigator/radiology review.
•6. Has not received prior treatment (chemotherapy, targeted therapy or radiotherapy) for their Stage III NSCLC.
•7. Has provided tumor tissue sample (tissue biopsy [core, incisional, or excisional]). FFPE blocks are preferred to slides. Newly obtained tumor sample is highly preferred over archival tissue and should be obtained prior to the thoracic imaging at screening.
•8. Has a performance status of 0 or 1 on the ECOG Performance Status assessed within 7 days prior to the first administration of study intervention.
•9. Has a life expectancy of at least 6 months.
•10. Has adequate PFT defined as a FEV1 >50% of predicted normal volume and the carbon monoxide lung diffusing capacity (DLCO) >40% of predicted normal value. Participants for whom DLCO measurements are not available will be deemed to have adequate oxygen transfer if pulse oximetry (O2 saturation) is determined to be =90% on room air.
•11. Has adequate organ function; all screening laboratory tests should be performed within 10 days prior to initiation of study intervention.
•12. Participants are at least 18 years of age on the day of providing informed consent.
•13.Male participants are eligible to participate if they agree to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception for each study intervention is as follows:
•-Olaparib and platinum doublet: 90 days
•Refrain from donating sperm
•PLUS either:
•-Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent
•-Must agree to use contraception as detailed below:
•Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant.
•14. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
•-is not a WOCBP
•Is a WOCBP and:
•Uses a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period. The length of time required to continue contraception for each study intervention is as follows:

排除标准

•1. Has SCLC or a mixed tumor with presence of small cell elements.
•2. Has MDS)/ (AML) or has features suggestive of MDS/AML.
•3. Has had documented weight loss >10% (from baseline) in the preceding 3 months.
•4. Is likely to have a radiation treatment plan that will encompass a volume of whole lung (total lung V20-GTV) receiving > 20 Gy in total (V20) of more than 34% of lung volume.
•5. Has received prior radiotherapy to the thorax, including radiotherapy to the esophagus,mediastinum, or for breast cancer.
•6. Has received 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).
•7. Has received prior therapy with olaparib or with any other PARP inhibitor.
•8. Had major surgery <4 weeks prior to the first dose of study medication (except for placement of vascular access).
•9. Is expected to require any other form of antineoplastic therapy, while on study.
•10.Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
•11. Has received colony-stimulating factors (e.g., G-CSF, GM-CSF, or recombinant erythropoietin) within 28 days prior to the first dose of study intervention.
•12. Is currently receiving either strong or moderate inducers of CYP3A4 that cannot be discontinued for the duration of the study. The required washout period prior to starting olaparib is 5 weeks for pentobarbital and 3 weeks for other agents.
•13. Is currently receiving either strong or moderate inhibitors of cytochrome P450 (CYP)3A4 that cannot be discontinued for the duration of the study. The required washout period prior to starting olaparib is 2 weeks.
•14. Pemetrexed-specific: Is unable to interrupt aspirin or other NSAIDs, other than an aspirin dose =1.3 grams per day, for at least 2 days (5 days for long-acting agents [for example, piroxicam]) before, during, and for at least 2 days after administration of pemetrexed.
•15. Pemetrexed-specific: Is unable/unwilling to take folic acid, vitamin B12, and dexamethasone.
•16.Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.
•17. The presence of uncontrolled, potentially reversible cardiac conditions, as judged by the investigator or participant has congenital long QT syndrome.
•18. 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 study medication.
•19. Has a known additional malignancy that is progressing or has required active treatment within the past 5 years.
•20. Has severe hypersensitivity (= Grade 3) to study intervention and/or any of its excipients
•21. Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
•22. Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease. Lymphangitic spread of the NSCLC is not exclusionary.
•23. Has an active infection re

研究者

发起方

Merck Sharp & Dohme LLC

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