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)

NCT06731907 | Recruiting Phase 2 FDA Drug

• 5 other identifiers: 3475-01G2024-515772-12-00U1111-1309-7532KEYMAKER U01MK-3475-01G
• Study Type: interventional
• Target: 90
• Locations: 11 countries
• Sites: 41

Brief Summary

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.

Conditions

Non-small Cell Lung Cancer

Keywords

Lung Neoplasms; Lung Cancer; Pulmonary Neoplasms; Pulmonary Cancer; Non-Small Cell Lung Carcinoma

Outcome Measures

Primary Outcomes (3)

• Overall Response Rate (ORR)

  ORR is defined as a confirmed complete response or partial response per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by Blinded Independent Central Review (BICR).

  Up to ~ 5 years

• Number of Participants with Adverse Events (AEs)

  Adverse events are any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.

  Up to ~ 5 years

• Number of Participants Discontinuing Study Drug Due to AEs

  Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.

  Up to ~ 2 years

Secondary Outcomes (3)

• Duration of Response (DOR)

  Up to ~ 5 years

• Progression-free Survival (PFS)

  Up to ~ 5 years

• Overall Survival (OS)

  Up to ~ 5 years

Study Arms (2)

Pembrolizumab and Chemotherapy

ACTIVE COMPARATOR

Pembrolizumab will be administered as a 200mg IV infusion on Day 1 of every three weeks (Q3W) for up to 35 cycles (\~ 2 years). The doublet platinum-based chemotherapy treatments used in this substudy are standard-of care regimens for squamous (paclitaxel/Nab-paclitaxel and carboplatin) and nonsquamous (pemetrexed and carboplatin) NSCLC. Pemetrexed is administered as a 500mg/m\^2 IV infusion Q3W until discontinuation criterion is met. Nab-paclitaxel will be administered as a 100mg/m\^2 IV infusion on Days 1, 8, and 15 Q3W for up to 4 cycles. Paclitaxel will be administered as a 200 mg/m\^2 IV infusion on Day 1 Q3W for up to 4 cycles. Carboplatin will be administered as an IV infusion area under the time x concentration curve (AUC) for 4 cycles as per local practice and labels. The dose will be AUC5 or 6 mg/mL•min Q3W and will not exceed 900mg.

Biological: Pembrolizumab; Drug: Carboplatin; Drug: Paclitaxel; Drug: Nab-paclitaxel; Drug: Pemetrexed

Pembrolizumab and HER3-DXd

EXPERIMENTAL

Pembrolizumab will be administered as a 200mg IV infusion on Day 1 Q3W for up to 35 cycles (\~ 2 years). HER3-Dxd will be administered as 5.6mg/kg IV infusion on Day 1 Q3W until discontinuation criteria is met.

Biological: Pembrolizumab; Biological: HER3-DXd

Interventions

Pembrolizumab BIOLOGICAL

Pembrolizumab 200mg IV Infusion.

Also known as: Keytruda®, MK-3475, SCH 900475

Pembrolizumab and Chemotherapy; Pembrolizumab and HER3-DXd

Carboplatin DRUG

Carboplatin IV infusion AUC5 or 6 mg/mL•min and not exceeding 900mg.

Also known as: Paraplatin®

Pembrolizumab and Chemotherapy

Paclitaxel DRUG

Paclitaxel 200 mg/m\^2 IV infusion.

Also known as: Taxol

Pembrolizumab and Chemotherapy

Nab-paclitaxel DRUG

Nab-paclitaxel 100mg/m\^2 IV infusion.

Also known as: Abraxane

Pembrolizumab and Chemotherapy

Pemetrexed DRUG

Pemetrexed 500mg/m\^2 IV infusion.

Also known as: Alimta

Pembrolizumab and Chemotherapy

HER3-DXd BIOLOGICAL

HER3-Dxd 5.6mg/kg IV infusion.

Also known as: patritumab deruxtecan, U3-1402, MK-1022

Pembrolizumab and HER3-DXd

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

• 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.

Sponsors & Collaborators

• Daiichi Sankyo: collaborator
• Merck Sharp & Dohme LLC: lead

Study Sites (41)

University of Kentucky ( Site 0019)

Lexington, Kentucky, 40536, United States

RECRUITING

MedStar Franklin Square Medical Center ( Site 0033)

Baltimore, Maryland, 21237, United States

RECRUITING

Sanford Fargo Medical Center ( Site 0039)

Fargo, North Dakota, 58102, United States

RECRUITING

Abramson Cancer Center ( Site 0010)

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Sanford Cancer Center ( Site 0038)

Sioux Falls, South Dakota, 57104, United States

RECRUITING

Centro de Estudios Clínicos SAGA ( Site 0162)

Santiago, Region M. de Santiago, 7500653, Chile

RECRUITING

FALP ( Site 0161)

Santiago, Region M. de Santiago, 7500921, Chile

RECRUITING

Bradfordhill ( Site 0160)

Santiago, Region M. de Santiago, 8420383, Chile

RECRUITING

THORACIC GENERAL HOSPITAL OF ATHENS "I SOTIRIA"-3rd Dept of Internal Medicine and Laboratory, Oncol ( Site 0204)

Athens, Attica, 115 27, Greece

RECRUITING

European Interbalkan Medical Center-Oncology Department ( Site 0205)

Thessaloniki, 570 01, Greece

RECRUITING

Petz Aladar Egyetemi Oktato Korhaz ( Site 0062)

Győr, Győr-Moson-Sopron, 9024, Hungary

RECRUITING

Jasz-Nagykun-Szolnok Megyei Hetenyi Gyula Korhaz-Rendelointezet ( Site 0061)

Szolnok, Jász-Nagykun-Szolnok, 5000, Hungary

RECRUITING

Országos Korányi Pulmonológiai Intézet ( Site 0060)

Budapest, 1121, Hungary

RECRUITING

Rambam Health Care Campus ( Site 0076)

Haifa, 3109601, Israel

RECRUITING

Shaare Zedek Medical Center ( Site 0075)

Jerusalem, 9103102, Israel

RECRUITING

Meir Medical Center ( Site 0071)

Kfar Saba, 4428164, Israel

RECRUITING

Rabin Medical Center ( Site 0074)

Petah Tikva, 4941492, Israel

RECRUITING

Sheba Medical Center ( Site 0070)

Ramat Gan, 5262000, Israel

RECRUITING

Sourasky Medical Center ( Site 0077)

Tel Aviv, 6423906, Israel

RECRUITING

Fondazione IRCCS Istituto Nazionale dei Tumori ( Site 0175)

Milan, Lombardy, 20133, Italy

RECRUITING

IRCCS Ospedale San Raffaele ( Site 0171)

Milan, 20132, Italy

RECRUITING

Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore ( Site 0174)

Roma, 00168, Italy

RECRUITING

Wielkopolskie Centrum Pulmonologii i Torakochirurgii-Oddzial Onkologii Klinicznej z Pododdzialem Dz ( Site 0153)

Poznan, Greater Poland Voivodeship, 60-569, Poland

ACTIVE NOT RECRUITING

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie ( Site 0151)

Warsaw, Masovian Voivodeship, 02-781, Poland

RECRUITING

Uniwersyteckie Centrum Kliniczne-Early Clinical Trials Unit ( Site 0150)

Gdansk, Pomeranian Voivodeship, 80-214, Poland

RECRUITING

Szpital Wojewódzki im. Mikoaja Kopernika w Koszalinie-Oddzial Dzienny Chemioterapii ( Site 0152)

Koszalin, West Pomeranian Voivodeship, 75-581, Poland

RECRUITING

Institut Català d'Oncologia - L'Hospitalet ( Site 0090)

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

RECRUITING

HOSPITAL CLÍNIC DE BARCELONA ( Site 0092)

Barcelona, 08008, Spain

RECRUITING

Hospital Universitario Quiron Madrid ( Site 0091)

Madrid, 28223, Spain

RECRUITING

Changhua Christian Hospital ( Site 0181)

Changhua, 50006, Taiwan

RECRUITING

Taipei Medical University Hospital ( Site 0180)

Taipei, 110, Taiwan

RECRUITING

Chang Gung Medical Foundation-Linkou Branch ( Site 0182)

Taoyuan, 33305, Taiwan

RECRUITING

Baskent University Dr. Turgut Noyan Research and Training Center ( Site 0141)

Adana, 01250, Turkey (Türkiye)

ACTIVE NOT RECRUITING

Hacettepe Universite Hastaneleri ( Site 0140)

Ankara, 06410, Turkey (Türkiye)

RECRUITING

Ankara Bilkent Şehir Hastanesi ( Site 0142)

Ankara, 06530, Turkey (Türkiye)

RECRUITING

CNE CC of Oncology Hematol ( Site 0130)

Cherkasy, Cherkasy Oblast, 18009, Ukraine

ACTIVE NOT RECRUITING

Municipal Enterprise "Bukovinian сlinical oncology сenter" ( Site 0136)

Chernivtsi, Chernivetska Oblast, 58013, Ukraine

RECRUITING

CNCE Precarpathian Clinical Oncologic Center ( Site 0131)

Ivano-Frankivsk, Ivano-Frankivsk Oblast, 76018, Ukraine

RECRUITING

VISION PARTNER Medical Centre ( Site 0134)

Kyiv, Kyivska Oblast, 03022, Ukraine

ACTIVE NOT RECRUITING

Communal Noncommercial Enterprise "Podillia Regional Oncology Center Of Vinnytsia Regional Council" ( Site 0133)

Vinnytsia, Vinnytsia Oblast, 21029, Ukraine

RECRUITING

Shalimov Institute of Surgery and Transplantation ( Site 0135)

Kyiv, 03126, Ukraine

RECRUITING

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

pembrolizumab; Carboplatin; Paclitaxel; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; Pemetrexed; patritumab deruxtecan

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Central Study Contacts

Toll Free Number

CONTACT

1-888-577-8839; Trialsites@msd.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a multi site, rolling-arm study.

Study Record Dates

• First Submitted: December 11, 2024
• First Posted: December 13, 2024
• Study Start: March 30, 2025
• Primary Completion (Estimated): March 12, 2032
• Study Completion (Estimated): March 12, 2032
• Last Updated: May 18, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share

Locations

CL (3); HU (3); IL (6); ES (3); TU (3); PL (4); GR (2); UA (6); IT (3); TW (3); US (5)