Study of Pembrolizumab With Concurrent Chemoradiation Therapy Followed by Pembrolizumab With or Without Olaparib in Stage III Non-Small Cell Lung Cancer (NSCLC) (MK-7339-012/KEYLYNK-012)

Running, not enrolling · Phase 3 · Has a placebo group

Conditions studied: Lung Neoplasms, Carcinoma, Non-Small-Cell Lung

In brief

The purpose of this study is to assess the efficacy and safety of pembrolizumab in combination with concurrent chemoradiation therapy followed by either pembrolizumab with olaparib placebo (Arm 1) or with olaparib (Arm 2) compared to concurrent chemoradiation therapy followed by durvalumab (Arm 3) in participants with unresectable, locally advanced NSCLC. Arms 1 and 2 will be studied in a double-blind design and Arm 3 will be open-label. The primary hypotheses are: 1. Pembrolizumab with concurrent chemoradiation therapy followed by pembrolizumab with olaparib is superior to concurrent chemoradiation therapy followed by durvalumab with respect to progression-free survival (PFS) and overall survival (OS) 2. Pembrolizumab with concurrent chemoradiation therapy followed by pembrolizumab is superior to concurrent chemoradiation therapy followed by durvalumab with respect to PFS and OS

Key facts

Study ID

NCT04380636

Run by

Merck Sharp & Dohme LLC

People needed

870

Starts

2020-07-06

Expected to finish

2029-07-06

Last updated by the study team

2026-05-15

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Has pathologically (histologically or cytologically) confirmed diagnosis of NSCLC
• Has Stage IIIA, IIIB, or IIIC NSCLC by American Joint Committee on Cancer Version 8
• Is unable to undergo surgery with curative intent for Stage III NSCLC
• Has no evidence of metastatic disease indicating Stage IV NSCLC
• Has measurable disease as defined by RECIST 1.1
• Has not received prior treatment (chemotherapy, targeted therapy or radiotherapy) for Stage III NSCLC; participants who have received neoadjuvant and/or adjuvant therapy for early stage disease are not eligible
• Has provided a tumor tissue sample (tissue biopsy [core, incisional, or excisional])
• Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 assessed within 7 days prior to the first administration of study intervention
• Has a life expectancy of at least 6 months
• A male participant must agree to use contraception and refrain from donating sperm during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention unless confirmed to be azoospermic (vasectomized or secondary to medical cause). The length of time required to continue contraception for each study intervention is as follows: Olaparib, platinum doublet, and radiotherapy: 90 days
• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and agrees to use contraception and refrain from donating eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during the treatment period and for at least the time needed to eliminate each study intervention after the last dose of study intervention and agrees to abstain from breastfeeding during the study intervention period and for at least 120 days after the last dose of study intervention. The length of time required to continue contraception for each study intervention is as follows: Pembrolizumab: 120 days; Olaparib, platinum doublet, and radiotherapy: 180 days
• Has a negative highly sensitive pregnancy test ([urine or serum] as required by local regulations) within 24 hours for urine or within 72 hours for serum before the first dose of study intervention. If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
• Has had her medical history, menstrual history, and recent sexual activity reviewed by the investigator to decrease the risk for inclusion of a woman with an early undetected pregnancy.
• Has adequate pulmonary function tests
• Has adequate organ function
• Has provided written informed consent

You may not qualify if…

• Has small cell lung cancer or a mixed tumor with presence of small cell elements
• Has myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or has features suggestive of MDS/AML
• Has had documented weight loss >10% (from baseline) in the preceding 3 months
• Has received prior radiotherapy to the thorax, including radiotherapy to the esophagus, mediastinum, or for breast cancer
• Has received prior therapy with an anti-programmed cell death 1 (ant-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), or anti- programmed cell death ligand 2 (anti-PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor
• Has received prior therapy with olaparib or with any other polyadenosine 5'diphosphoribose (polyADP ribose) polymerization (PARP) inhibitor
• Has had major surgery <4 weeks prior to the first dose of study treatment (except for placement of vascular access)
• Is expected to require any other form of antineoplastic therapy, while on study
• Has received a live or live attenuated vaccine within 30 days before the first dose of study intervention; administration of killed vaccines is allowed
• Has received colony-stimulating factors (e.g., granulocyte colony-stimulating factor [GCSF], granulocyte-macrophage colony-stimulating factor [GM-CSF] or recombinant erythropoietin) within 28 days prior to the first dose of study treatment
• Is currently receiving either strong (phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate (e.g. bosentan, efavirenz, modafinil) inducers of CYP3A4 that cannot be discontinued for the duration of the study
• Is currently receiving either strong (eg, itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate (eg. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil) inhibitors of cytochrome P450 (CYP)3A4 that cannot be discontinued for the duration of the study
• Is unable to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs), other than an aspirin dose ≤1.3 grams per day, for at least 2 days before, during, and for at least 2 days after administration of pemetrexed
• Is unable/unwilling to take folic acid, vitamin B12, and dexamethasone during administration of pemetrexed
• Has received an investigational agent or has used an investigational device within 4 weeks prior to study treatment
• The presence of uncontrolled, potentially reversible cardiac conditions, as judged by the investigator or has congenital long QT syndrome
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study intervention
• Has a known additional malignancy that is progressing or has required active treatment within the past 5 years with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ (excluding carcinoma-in situ-of the bladder) that have undergone potentially curative therapy
• Has severe hypersensitivity (≥Grade 3) to study intervention and/or any of its excipients
• Has an active autoimmune disease that has required systemic treatment in past 2 years
• Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
• Has an active infection requiring systemic therapy
• Has a known history of human immunodeficiency virus (HIV) infection
• Has a known history of Hepatitis B or known active Hepatitis C virus infection
• Has active tuberculosis (TB; Mycobacterium tuberculosis) and is receiving treatment

Where it is running

• St. Bernards Medical Center ( Site 0089) — Jonesboro, Arkansas, United States
• St Joseph Heritage Healthcare-Oncology ( Site 0088) — Fullerton, California, United States
• Long Beach Memorial Medical Center ( Site 0006) — Long Beach, California, United States
• UCLA Hematology/Oncology - Santa Monica ( Site 0013) — Los Angeles, California, United States
• St. Joseph Heritage Healthcare Local Lab ( Site 0011) — Santa Rosa, California, United States
• Torrance Memorial Physician Network / Cancer Center ( Site 0093) — Torrance, California, United States
• Memorial Regional Hospital-Memorial Cancer Institute ( Site 0095) — Hollywood, Florida, United States
• Miami VA Healthcare System ( Site 0024) — Miami, Florida, United States
• Mid Florida Hematology and Oncology Center ( Site 0022) — Orange City, Florida, United States
• Orlando Health, UF Health Cancer Center Inc ( Site 0092) — Orlando, Florida, United States
• Fort Wayne Medical Oncology and Hematology ( Site 0094) — Fort Wayne, Indiana, United States
• Parkview Research Center ( Site 0032) — Fort Wayne, Indiana, United States
• Franciscan Health Lafayette East ( Site 0031) — Lafayette, Indiana, United States
• University of Kentucky ( Site 0096) — Lexington, Kentucky, United States
• Norton Brownsboro Hospital-Norton Cancer Institute - Brownsboro ( Site 0035) — Louisville, Kentucky, United States
• Pikeville Medical Center ( Site 0036) — Pikeville, Kentucky, United States
• Massachusetts General Hospital ( Site 0038) — Boston, Massachusetts, United States
• Henry Ford Hospital ( Site 0045) — Detroit, Michigan, United States
• VA St. Louis Health Care System ( Site 0047) — St Louis, Missouri, United States
• Washington University Siteman Cancer Center ( Site 0046) — St Louis, Missouri, United States
• CHI Health St. Francis ( Site 0053) — Grand Island, Nebraska, United States
• Rutgers Cancer Institute of New Jersey ( Site 0054) — New Brunswick, New Jersey, United States
• Valley Health Systems - Ridgewood Campus ( Site 0056) — Paramus, New Jersey, United States
• Montefiore Einstein Center ( Site 0083) — The Bronx, New York, United States
• University of South Alabama, Mitchell Cancer Institute ( Site 0003) — Mobile, Alabama, United States

Full record on ClinicalTrials.gov

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