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Clinical Trials in the UK / NCT04380636
Active, not recruiting Phase 3

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)

NCT04380636 · tracked via the Priya Life Science UK tracker
Sponsor
Merck Sharp & Dohme LLC
Phase
Phase 3
Started
2020-07-06
Last updated
2026-05-15

Condition(s) studied

Lung NeoplasmsCarcinoma, Non-Small-Cell Lung

Investigational drug(s) / intervention(s)

PembrolizumabOlaparibPlacebo for olaparibEtoposideCarboplatinCisplatinPaclitaxelPemetrexedThoracic RadiotherapyDurvalumab

Pembrolizumab: intravenous (IV) infusion

Olaparib: oral tablets

Placebo for olaparib: oral tablets

Etoposide: IV infusion

Carboplatin: IV infusion

Cisplatin: IV infusion

Paclitaxel: IV infusion

Pemetrexed: IV infusion

Thoracic Radiotherapy: external beam radiation

Durvalumab: IV infusion

Study summary

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

Eligibility

Sex
ALL
Min age
18 Years
Max age
Healthy volunteers
No
Inclusion Criteria: * 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 Exclusion Criteria: * 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 * Has a history or current evidence of any condition, therapy, laboratory abnormality or other circumstance that might confound the results of the study, or interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator * Is considered a poor medical risk due to a serious, uncontrolled medical disorder or nonmalignant systemic disease in the opinion of the treating investigator * Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study * Is unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption * Has had an allogenic tissue/solid organ transplant

Primary outcome measure(s)

Trial sites (205)

FacilityCityRegionStatus
University of South Alabama, Mitchell Cancer Institute ( Site 0003) Mobile Alabama
St. Bernards Medical Center ( Site 0089) Jonesboro Arkansas
St Joseph Heritage Healthcare-Oncology ( Site 0088) Fullerton California
Long Beach Memorial Medical Center ( Site 0006) Long Beach California
UCLA Hematology/Oncology - Santa Monica ( Site 0013) Los Angeles California
St. Joseph Heritage Healthcare Local Lab ( Site 0011) Santa Rosa California
Torrance Memorial Physician Network / Cancer Center ( Site 0093) Torrance California
Memorial Regional Hospital-Memorial Cancer Institute ( Site 0095) Hollywood Florida
Miami VA Healthcare System ( Site 0024) Miami Florida
Mid Florida Hematology and Oncology Center ( Site 0022) Orange City Florida
Orlando Health, UF Health Cancer Center Inc ( Site 0092) Orlando Florida
Fort Wayne Medical Oncology and Hematology ( Site 0094) Fort Wayne Indiana
Parkview Research Center ( Site 0032) Fort Wayne Indiana
Franciscan Health Lafayette East ( Site 0031) Lafayette Indiana
University of Kentucky ( Site 0096) Lexington Kentucky
Norton Brownsboro Hospital-Norton Cancer Institute - Brownsboro ( Site 0035) Louisville Kentucky
Pikeville Medical Center ( Site 0036) Pikeville Kentucky
Massachusetts General Hospital ( Site 0038) Boston Massachusetts
Henry Ford Hospital ( Site 0045) Detroit Michigan
VA St. Louis Health Care System ( Site 0047) St Louis Missouri
Washington University Siteman Cancer Center ( Site 0046) St Louis Missouri
CHI Health St. Francis ( Site 0053) Grand Island Nebraska
Rutgers Cancer Institute of New Jersey ( Site 0054) New Brunswick New Jersey
Valley Health Systems - Ridgewood Campus ( Site 0056) Paramus New Jersey
Montefiore Einstein Center ( Site 0083) The Bronx New York
Novant Health Presbyterian ( Site 0081) Charlotte North Carolina
Duke University Medical Center ( Site 0050) Durham North Carolina
Piedmont Hematology-Oncology Associates ( Site 0080) Winston-Salem North Carolina
The Lindner Center for Research and Education at The Christ Hospital ( Site 0060) Cincinnati Ohio
Fox Chase Cancer Center ( Site 0063) Philadelphia Pennsylvania
Sanford Cancer Center Oncology Clinic ( Site 0066) Sioux Falls South Dakota
Veterans Affairs Puget Sound Health Care System [Seattle, WA] ( Site 0075) Seattle Washington
Cancer Care Northwest ( Site 0074) Spokane Valley Washington
Clinica Adventista Belgrano-Oncology ( Site 4002) Caba. Buenos Aires
Instituto Médico Río Cuarto ( Site 4003) Río Cuarto Córdoba Province
Queen Elizabeth II Health Sciences Centre ( Site 0100) Halifax Nova Scotia
Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0102) Montreal Quebec
CIUSSS Ouest de l Ile - St-Mary s Hospital ( Site 0108) Montreal Quebec
McGill University Health Center - Research Institute ( Site 0114) Montreal Quebec
Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0110) Québec Quebec

+ 165 more sites — see the full list on the official registry below.

On this site

📄 Keytruda (pembrolizumab) drug profile → 📄 Lynparza (olaparib) drug profile → 📄 Imfinzi (durvalumab) drug profile →

More Merck Sharp & Dohme LLC trials in the UK

Other trials for the same condition

Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT04380636 on ClinicalTrials.gov ↗ ← All trials in the UK