A Study of Pembrolizumab With or Without Chemotherapy in Combination With Additional Treatments for Advanced Non-Small Cell Lung Cancer (NSCLC) (MK-3475-01G/KEYMAKER U01)

Recruiting now · Phase 2

Conditions studied: Non-small Cell Lung Cancer

In brief

Researchers are investigating new treatments for untreated advanced non-small cell lung cancer (NSCLC), which is the most common form of lung cancer and lung cancer that has spread beyond surgical removal. Standard treatments include immunotherapy, such as pembrolizumab, and chemotherapy. This study aims to determine the effectiveness of adding other treatments, including the human epidermal growth factor receptor 3-directed antibody-drug conjugate (HER3-DXd) patritumab deruxtecan, to pembrolizumab, with or without chemotherapy. The primary goals are to assess safety and efficacy of the treatments.

Key facts

Study ID

NCT06731907

Run by

Merck Sharp & Dohme LLC

People needed

90

Starts

2025-03-30

Expected to finish

2032-03-12

Last updated by the study team

2026-05-26

Who can join

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

You may qualify if…

• The main inclusion criteria include but are not limited to the following:
• Histologically or cytologically confirmed diagnosis of Stage IV squamous or non-squamous non-small cell lung cancer (NSCLC) per American Joint Committee on Cancer (AJCC) Staging Manual Version 8.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of either 0 or 1 as assessed within 7 days before randomization.
• Has archival tumor tissue sample or newly obtained core, incisional, or excisional biopsy of a tumor lesion not previously irradiated has been provided.
• Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on ART.
• Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to treatment randomization.

You may not qualify if…

• The main exclusion criteria include but are not limited to the following:
• Has a diagnosis of small cell lung cancer or, for mixed tumors, presence of small cell elements.
• Participants with squamous histology are excluded if there is a known tumor-activating epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) or c ros oncogene 1 (ROS1) gene rearrangement.
• Is HIV-infected with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
• Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder, or any autoimmune, connective tissue, or inflammatory disorders with pulmonary involvement.
• Has evidence of any leptomeningeal disease.
• Has known history of, or active, neurologic paraneoplastic syndrome.
• Has clinically significant corneal disease.
• Has myocardial infarction within 6 months.
• Has New York Heart Association (NYHA) Classes 3 or 4 congestive heart failure.
• Has uncontrolled angina pectoris within 6 months.
• Has cardiac arrhythmia requiring ongoing antiarrhythmic treatment.
• Has history of clinically relevant ventricular arrhythmias, such as ventricular tachycardia, ventricular fibrillation, or Torsade de Pointes.
• Has bradycardia of less than 50 beats per minute (bpm) unless the participant has a pacemaker.
• Has history of second- or third-degree heart block. Candidates with a history of heart block may be eligible if they currently have pacemakers and have no history of fainting or clinically relevant arrhythmia with pacemakers.
• Has coronary/peripheral artery bypass graft within 6 months.
• Has complete left bundle branch block.
• Has inadequate washout period from prior concomitant therapy as specified in protocol before randomization.
• Has received prior treatment with a topoisomerase I inhibitor or an anti-HER3 antibody and/or ADC that consists of an exatecan derivative that is a topoisomerase I inhibitor.
• Has received prior systemic anticancer therapy for their metastatic NSCLC.
• Has received prior therapy with an anti- programmed cell death 1 protein (anti-PD-1), anti- programmed cell death ligand 1 protein (anti-PD-L1), or anti- programmed cell death ligand 2 protein (anti-PD-L2) agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor.
• Has received prior radiotherapy within 2 weeks of randomization, has radiation related toxicity requiring corticosteroids, or has had radiation pneumonitis.
• Has received radiation therapy to the lung that is >30 gray within 6 months of start of study intervention.
• Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.
• Has diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention.

Where it is running

• Taipei Medical University Hospital ( Site 0180) — Taipei, Taiwan (enrolling)
• MedStar Franklin Square Medical Center ( Site 0033) — Baltimore, Maryland, United States (enrolling)
• Sanford Fargo Medical Center ( Site 0039) — Fargo, North Dakota, United States (enrolling)
• Abramson Cancer Center ( Site 0010) — Philadelphia, Pennsylvania, United States (enrolling)
• Sanford Cancer Center ( Site 0038) — Sioux Falls, South Dakota, United States (enrolling)
• Centro de Estudios Clínicos SAGA ( Site 0162) — Santiago, Region M. de Santiago, Chile (enrolling)
• FALP ( Site 0161) — Santiago, Region M. de Santiago, Chile (enrolling)
• Bradfordhill ( Site 0160) — Santiago, Region M. de Santiago, Chile (enrolling)
• THORACIC GENERAL HOSPITAL OF ATHENS "I SOTIRIA"-3rd Dept of Internal Medicine and Laboratory, Oncol ( Site 0204) — Athens, Attica, Greece (enrolling)
• European Interbalkan Medical Center-Oncology Department ( Site 0205) — Thessaloniki, Greece (enrolling)
• Petz Aladar Egyetemi Oktato Korhaz ( Site 0062) — Győr, Győr-Moson-Sopron, Hungary (enrolling)
• Jasz-Nagykun-Szolnok Varmegyei Hetenyi Geza Korhaz-Rendelointezet ( Site 0061) — Szolnok, Jász-Nagykun-Szolnok, Hungary (enrolling)
• Országos Korányi Pulmonológiai Intézet ( Site 0060) — Budapest, Hungary (enrolling)
• Rambam Health Care Campus ( Site 0076) — Haifa, Israel (enrolling)
• Shaare Zedek Medical Center ( Site 0075) — Jerusalem, Israel (enrolling)
• Meir Medical Center ( Site 0071) — Kfar Saba, Israel (enrolling)
• Rabin Medical Center ( Site 0074) — Petah Tikva, Israel (enrolling)
• Sheba Medical Center ( Site 0070) — Ramat Gan, Israel (enrolling)
• Sourasky Medical Center ( Site 0077) — Tel Aviv, Israel (enrolling)
• Fondazione IRCCS Istituto Nazionale dei Tumori ( Site 0175) — Milan, Lombardy, Italy (enrolling)
• IRCCS Ospedale San Raffaele ( Site 0171) — Milan, Italy (enrolling)
• Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore ( Site 0174) — Roma, Italy (enrolling)
• Municipal Enterprise "Bukovinian сlinical oncology сenter" ( Site 0136) — Chernivtsi, Chernivetska Oblast, Ukraine (enrolling)
• CNCE Precarpathian Clinical Oncologic Center ( Site 0131) — Ivano-Frankivsk, Ivano-Frankivsk Oblast, Ukraine (enrolling)
• Communal Noncommercial Enterprise "Podillia Regional Oncology Center Of Vinnytsia Regional Council" ( Site 0133) — Vinnytsia, Vinnytsia Oblast, Ukraine (enrolling)

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.