Pembrolizumab (MK-3475) Plus Investigational Agents in Resectable Non-small Cell Lung Cancer (NSCLC) (MK-3475-01E/KEYMAKER-U01)

NCT06788912 | Recruiting Phase 2 FDA Drug

• 5 other identifiers: 3475-01EMK-3475-01EKEYMAKER-U012023-509234-19-00U1111-1299-6753
• Study Type: interventional
• Target: 60
• Locations: 9 countries
• Sites: 34

Brief Summary

The main goals are after treatment given before surgery, to measure the number of people who have no signs of cancer cells in tumors and lymph nodes removed during surgery; and to learn about whether the cancer gets smaller or goes away by measuring the number of people with a certain number of living cancer cells in the tumor removed during surgery.

Conditions

Lung Neoplasm Malignant

Keywords

Programmed Cell Death-1 (PD1, PD-1); Programmed Cell Death 1 Ligand 1(PDL1, PD-L1); Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)

Outcome Measures

Primary Outcomes (2)

• Pathological Complete Response (pCR)

  pCR is defined as absence of residual viable invasive cancer on hematoxylin- and eosin-stained slides of the resected lung specimen and lymph nodes.

  Up to approximately 20 weeks

• Percent Residual Viable Tumor (%RVT)

  %RVT is defined as the percentage of residual tumor estimated by comparing the estimated cross-sectional area of viable tumor with estimated cross-sectional areas of remainder of tumor bed. The tumor bed is defined as the area of tissue occupied by viable tumor or tumoral regression (includes areas of necrosis, foamy macrophages, giant cell reaction, cholesterol cleft granuloma, and inflammation.)

  Up to approximately 20 weeks

Secondary Outcomes (11)

• Percentage of Participants Who Report at Least 1 Adverse Event (AE)

  Up to approximately 5 years

• Percentage of Participants Who Discontinue Study Treatment Due to an AE

  Up to approximately 1 year

• Event-free Survival (EFS)

  Up to approximately 5 years

• Overall Survival (OS)

  Up to approximately 5 years

• Distant Metastasis-Free Survival (DMFS)

  Up to approximately 5 years

Study Arms (2)

Pembrolizumab + Platinum

ACTIVE COMPARATOR

Neoadjuvant: Prior to surgery pembrolizumab 200 mg every three weeks (Q3W) for 4 cycles (each cycle is 21 days); Cisplatin 75 mg/m\^2 Q3W with gemcitabine 1000 mg/m\^2 on Day 1 and Day 8 Q3W (squamous tumors), pemetrexed 500 mg/m\^2 Q3W (nonsquamous tumors), or paclitaxel 175 mg/m\^2 or 200 mg/m\^2 q3w (any histology) OR Carboplatin AUC 5 mg/mL• min or AUC 6 mg/mL• min with paclitaxel 175 mg/m\^2 or 200 mg/m\^2 Q3W (any histology), pemetrexed 500 mg/m\^2 Q3W (nonsquamous tumors), or gemcitabine 1000 mg/m\^2 on Day 1 and Day 8 Q3W (squamous tumors); followed by surgery. Adjuvant: After surgery pembrolizumab 200 mg Q3W for 13 cycles (each cycle is 21 days).

Biological: Pembrolizumab (neoadjuvant); Drug: Cisplatin; Drug: Gemcitabine; Drug: Pemetrexed; Drug: Carboplatin; Biological: Pembrolizumab (adjuvant); Drug: Paclitaxel

Pembrolizumab + Sacituzumab tirumotecan

EXPERIMENTAL

Neoadjuvant: Prior to surgery pembrolizumab 200 mg Q3W for 4 cycles (each cycle is 21 days); sacituzumab tirumotecan 4 mg/kg Q2W for 6 cycles (each cycle is 14 days), followed by surgery. Adjuvant: After surgery pembrolizumab 200 mg Q3W for 13 cycles (each cycle is 21 days). Optional adjuvant platinum-based doublet chemotherapy up to 4 cycles may be given at the investigator's discretion.

Biological: Pembrolizumab (neoadjuvant); Drug: Cisplatin; Drug: Gemcitabine; Drug: Pemetrexed; Drug: Sacituzumab tirumotecan; Drug: H1 receptor antagonist; Drug: H2 receptor antagonist; Drug: Acetaminophen (or equivalent); Drug: Dexamethasone (or equivalent); Drug: Carboplatin; Biological: Pembrolizumab (adjuvant); Drug: Paclitaxel; Drug: Steroid mouthwash (dexamethasone or equivalent)

Interventions

Pembrolizumab (neoadjuvant) BIOLOGICAL

Before surgery neoadjuvant Pembrolizumab 200 mg by intravenous (IV) infusion on day 1 of each 21-day cycle for 4 cycles

Also known as: KEYTRUDA®, MK-3475

Pembrolizumab + Platinum; Pembrolizumab + Sacituzumab tirumotecan

Cisplatin DRUG

Cisplatin 75 mg/m\^2 by IV infusion on day 1 of each 21-day cycle for 4 cycles

Also known as: PLATINOL®

Pembrolizumab + Platinum; Pembrolizumab + Sacituzumab tirumotecan

Gemcitabine DRUG

In squamous tumors Gemcitabine 1000 mg/m\^2 by IV infusion on day 1 and day 8 of each 21-day cycle for 4 cycles.

Also known as: GEMZAR®

Pembrolizumab + Platinum; Pembrolizumab + Sacituzumab tirumotecan

Pemetrexed DRUG

In nonsquamous tumors Pemetrexed 500 mg/m\^2 by IV infusion on day 1 of each 21-day cycle for 4 cycles

Also known as: Alimta®

Pembrolizumab + Platinum; Pembrolizumab + Sacituzumab tirumotecan

Sacituzumab tirumotecan DRUG

Sacituzumab tirumotecan 4 mg/kg by IV infusion on day 1 of each 14-day cycle for up to 6 cycles

Also known as: MK-2870, SKB264

Pembrolizumab + Sacituzumab tirumotecan

H1 receptor antagonist DRUG

Administered as rescue medication before Sacituzumab tirumotecan infusion per approved product label

Pembrolizumab + Sacituzumab tirumotecan

H2 receptor antagonist DRUG

Administered as rescue medication before Sacituzumab tirumotecan infusion per approved product label

Pembrolizumab + Sacituzumab tirumotecan

Acetaminophen (or equivalent) DRUG

Administered as rescue medication before Sacituzumab tirumotecan infusion per approved product label

Pembrolizumab + Sacituzumab tirumotecan

Dexamethasone (or equivalent) DRUG

Administered as rescue medication 8 -10 mg before Sacituzumab tirumotecan infusion per approved product label

Pembrolizumab + Sacituzumab tirumotecan

Carboplatin DRUG

AUC 5 mg/mL min or AUC 6 mg/mL min by IV infusion on day 1 of each 21-day cycle for 4 cycles

Also known as: PARAPLATIN®

Pembrolizumab + Platinum; Pembrolizumab + Sacituzumab tirumotecan

Pembrolizumab (adjuvant) BIOLOGICAL

After surgery adjuvant Pembrolizumab 200 mg by IV infusion on day 1 of each 21-day cycle for 13 cycles

Also known as: KEYTRUDA®, MK-3475

Pembrolizumab + Platinum; Pembrolizumab + Sacituzumab tirumotecan

Paclitaxel DRUG

Paclitaxel 175 or 200 mg/m\^2 by IV infusion on day 1 of each 21-day cycle for 4 cycles.

Pembrolizumab + Platinum; Pembrolizumab + Sacituzumab tirumotecan

Steroid mouthwash (dexamethasone or equivalent) DRUG

Administered orally as rescue medication 2-5 mL 4 times daily

Pembrolizumab + Sacituzumab tirumotecan

Eligibility Criteria

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

You may not qualify if:

• Has previously untreated and pathologically confirmed resectable Stage II, IIIA, or IIIB (N2) non-small cell lung cancer (NSCLC)
• Able to undergo protocol therapy, including necessary surgery
• Confirmation that epidermal growth factor receptor (EGFR) -directed therapy is not indicated as primary therapy
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of either 0 or 1 as assessed within 10 days before initiation of study intervention.
• Is able to provide archival or newly obtained core/excisional biopsy of the primary lung tumor or lymph node metastasis.
• Has one of the following tumor locations/types: NSCLC involving the superior sulcus, large-cell neuro-endocrine cancer, mixed tumors containing small cell and non-small cell elements, or sarcomatoid tumor.
• Has Grade ≥2 peripheral neuropathy.
• Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing.
• Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, or chronic diarrhea).
• Has uncontrolled, significant cardiovascular disease or cerebrovascular disease.
• Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
• Received prior radiotherapy within 2 weeks of start of study intervention, or radiation related toxicities, requiring corticosteroids.
• 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 to the first dose of study intervention.
• Known additional malignancy that is progressing or has required active treatment within the past 5 years.
• Severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (34)

Southern Cancer Center (SCC) ( Site 8004)

Daphne, Alabama, 36526, United States

RECRUITING

Sansum Clinic (Ridley Tree) ( Site 8012)

Santa Barbara, California, 93105, United States

RECRUITING

Rocky Mountain Cancer Centers (RMCC) ( Site 8011)

Lone Tree, Colorado, 80124, United States

RECRUITING

MedStar Franklin Square Medical Center ( Site 0033)

Baltimore, Maryland, 21237, United States

RECRUITING

Oncology Associates of Oregon, P.C.(Willamette Valley Cancer Institute) (WVCI) ( Site 8006)

Eugene, Oregon, 97401, United States

RECRUITING

Texas Oncology - Central/South Texas ( Site 8009)

Austin, Texas, 78705, United States

RECRUITING

Texas Oncology - Northeast Texas ( Site 8005)

Tyler, Texas, 75702, United States

RECRUITING

Virginia Cancer Specialists (VCS) ( Site 8002)

Fairfax, Virginia, 22031, 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

Alexandra General Hospital of Athens Oncology-Hematology Unit ( Site 0203)

Athens, Attica, 115 28, Greece

RECRUITING

ATTIKON GENERAL UNIVERSITY HOSPITAL-Oncology ( Site 0202)

Athens, Attica, 12462, Greece

RECRUITING

Metropolitan Hospital-4th Oncology Dept ( Site 0201)

Athens, Attica, 185 47, Greece

RECRUITING

University General Hospital of Heraklion ( Site 0200)

Heraklion, Irakleio, 71110, Greece

RECRUITING

Petz Aladar Egyetemi Oktato Korhaz-Pulmonológia (Dr. Szalai Zsuzsanna) ( Site 0062)

Győr, Győr-Moson-Sopron, 9024, Hungary

RECRUITING

Jász-Nagykun-Szolnok Vármegyei Hetényi Géza Kórház-Onkologiai Kozpont ( Site 0061)

Szolnok, Jász-Nagykun-Szolnok, 5000, Hungary

RECRUITING

Országos Korányi Pulmonológiai Intézet ( Site 0060)

Budapest, 1121, Hungary

RECRUITING

Azienda Ospedaliera Universitaria Careggi ( Site 0173)

Florence, Tuscany, 50134, Italy

RECRUITING

Ospedale San Raffaele. ( Site 0171)

Milan, 20132, Italy

RECRUITING

Fondazione IRCCS Istituto Nazionale dei Tumori ( Site 0175)

Milan, 20133, 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

RECRUITING

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworow Pluca i Klatki Pier ( Site 0151)

Warsaw, Masovian Voivodeship, 02-781, Poland

RECRUITING

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

Gdansk, Pomeranian Voivodeship, 80-952, Poland

RECRUITING

Hospital Clínic de Barcelona ( Site 0092)

Barcelona, 08008, Spain

RECRUITING

Hacettepe Universite Hastaneleri-oncology hospital ( Site 0700)

Ankara, 06230, Turkey (Türkiye)

RECRUITING

CNE CC of Oncology Hematol ( Site 0130)

Cherkasy, Cherkasy Oblast, 18009, Ukraine

RECRUITING

Municipal Enterprise "Bukovinian сlinical oncology сenter" ( Site 0139)

Chernivtsi, Chernivetska Oblast, 58013, Ukraine

RECRUITING

CNCE Precarpathian Clinical Oncologic Center ( Site 0131)

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

RECRUITING

MNPE LTMU Multidisc. Clin. Hosp. of Emerg. and Intens. Care ( Site 0132)

Lviv, Lviv Oblast, 79059, Ukraine

RECRUITING

ME RIVNE REGIONAL ANTITUMOR CENTER ( Site 0460)

Rivne, Rivne Oblast, 33010, Ukraine

RECRUITING

Communal Noncommercial Enterprise "Podillia Regional Oncology Center Of Vinnytsia Regional Council" ( Site 0135)

Vinnytsia, Vinnytsia Oblast, 21029, Ukraine

RECRUITING

Shalimov Institute of Surgery and Transplantation ( Site 0138)

Kyiv, 03126, Ukraine

RECRUITING

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Lung Neoplasms; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab; Neoadjuvant Therapy; Cisplatin; Gemcitabine; Pemetrexed; Histamine Antagonists; Histamine H2 Antagonists; Acetaminophen; Dexamethasone; Carboplatin; Adjuvants, Pharmaceutic; Paclitaxel

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Histamine Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Physiological Effects of Drugs; Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Coordination Complexes; Pharmaceutic Aids; Pharmaceutical Preparations; Specialty Uses of Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

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: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2025
• First Posted: January 23, 2025
• Study Start: March 20, 2025
• Primary Completion (Estimated): February 6, 2032
• Study Completion (Estimated): February 6, 2032
• Last Updated: March 31, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

ES (1); GR (4); TU (1); UA (7); US (8); PL (3); IT (4); CL (3); HU (3)