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RecruitingInterventionalPhase 3

A Phase 3 Randomized Open-Label Study of Adjuvant Pembrolizumab With or Without MK-2870 in Participants With Resectable Stage II to IIIB (N2) NSCLC Not Achieving pCR After Receiving Neoadjuvant Pembrolizumab With Platinum-based Doublet Chemotherapy Followed by Surgery

NCT ID: NCT06312137Sponsor: Merck Sharp & Dohme LLCLast updated: 2026-05-22

Summary

This study will assess if adding sacituzumab tirumotecan with pembrolizumab after surgery is effective in treating NSCLC for participants not achieving pathological complete response. The primary hypothesis of this study is sacituzumab tirumotecan plus pembrolizumab is superior to pembrolizumab monotherapy with respect to disease free survival (DFS) as assessed by blinded independent central review (BICR).

Arms & interventions

  • BiologicalSacituzumab tirumotecan

    Sacituzumab tirumotecan to be administered as 4mg/kg IV infusion q2w for up to 24 weeks

  • BiologicalPembrolizumab

    Pembrolizumab to be administered 400mg by IV infusion q6w for up to 42 weeks

  • DrugCisplatin

    Cisplatin is administered as 75 mg/m2 IV infusion q3w for up to 12 weeks as background treatment in neoadjuvant phase

  • DrugPemetrexed

    Pemetrexed will be administered in the neoadjuvant phase as 500 mg/m2 IV infusion q3w for up to 12 weeks as background treatment in participants with nonsquamous NSCLC.

  • DrugGemcitabine

    Gemcitabine will be administered in the neoadjuvant phase as 1000 mg/m2 or 1250 mg/m2 IV infusion on day 1 and day 8 q3w for up to 24 weeks as background treatment in participants with squamous NSCLC.

  • DrugCarboplatin

    Carboplatin will be administered in the neoadjuvant phase as AUC 5 mg/mL/min or AUC 6 mg/mL/min IV infusion q3w for up to 12 weeks as background treatment.

  • DrugPaclitaxel

    Paclitaxel will be administered in the neoadjuvant phase as 175 mg/m2 or 200 mg/m2 IV infusion q3w for up to 12 weeks as background treatment.

  • DrugRescue medication

    Participants are allowed to take rescue medication to prevent hypersensitivity and/or infusion reactions as a premedication to study treatment. At the discretion of the investigator, participants are provided with a prescription for rescue medications. Recommended rescue medications are antihistamine, H2 receptor antagonist, acetaminophen or equivalent, dexamethasone or equivalent. A steroid mouthwash (dexamethasone or equivalent) may be given as prophylaxis for stomatitis/oral mucositis.

Outcome measures

Primary

  • Disease-free survival (DFS) as assessed by Blinded Independent Central Review (BICR)

    DFS is defined as the time from randomization to any recurrence (local, locoregional, regional or distant), occurrence of new primary NSCLC, or death due to any cause, whichever occurs first.

    Time frame: Up to ~ 93 months

Secondary

  • Overall Survival (OS)

    Time frame: Up to ~ 118 months

  • Distant metastasis-free survival (DMFS) as assessed by investigator

    Time frame: Up to ~ 118 months

  • Disease-Free Survival (DFS) as assessed by investigator

    Time frame: Up to ~ 118 months

  • Lung Cancer Specific Survival (LCSS)

    Time frame: Up to ~ 118 months

  • Number of Participants Who Experience an Adverse Event (AE)

    Time frame: Up to ~ 118 months

  • Number of Participants Who Discontinue Study Intervention Due to AEs

    Time frame: Up to ~ 118 months

  • Change from Baseline in Global Health Status/Quality of Life (QoL) score (Quality of Life Questionnaire (QLQ)-C30 Items 29 and 30)

    Time frame: Baseline and up to ~118 months

  • Change from Baseline in Physical Functioning Score (QLQ-C30 Items 1 to 5)

    Time frame: Baseline and up to ~118 months

  • Change from Baseline in Role Functioning Score (QLQ-C30 Items 6 and 7)

    Time frame: Baseline and up to ~118 months

  • Change from Baseline in Dyspnea scores (QLQ-C30 Item 8)

    Time frame: Baseline and up to ~118 months

  • Change from Baseline in Coughing scores (QLQ-LC24 Items 31 and 52)

    Time frame: Baseline and up to ~118 months

  • Change from Baseline in Chest pain scores (QLQ-LC24 Item 40)

    Time frame: Baseline and up to ~118 months

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
The key inclusion and exclusion criteria include but are not limited to the following: Inclusion Criteria: * Has histological or cytological confirmation of squamous or nonsquamous non-small cell lung cancer (NSCLC), resectable clinical Stage II, IIIA or IIIB (with nodal involvement \[N2\]) per AJCC eighth edition guidelines * Has confirmation that either epidermal growth factor receptor (EGFR)-directed or anaplastic lymphoma kinase (ALK)-directed therapy is not indicated as primary therapy * Is able to undergo surgery based on opinion of investigator after consultation with surgeon * Is able to receive neoadjuvant pembrolizumab and platinum-based doublet chemotherapy * Applies to screening for the adjuvant period only, before randomization: Has not achieved pathological complete response (pCR) at surgery by local review of pathology. * Applies to screening for the adjuvant period only, before randomization: Tumor tissue sample from surgical resection has been provided for determination of programmed cell death ligand 1 (PD-L1) and trophoblast cell surface antigen 2 (TROP2) status by central vendor before randomization into the adjuvant period * Applies to screening for the adjuvant period only, before randomization: Confirmed to be disease-free based on re-baseline radiological assessment as documented by contrast enhanced chest/abdomen/pelvis computed tomography (CT) (or magnetic resonance imaging (MRI)) within 28 days before randomization * Participants who have AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline. Participants with endocrine-related AEs who are adequately treated with hormone replacement are eligible * Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (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 at screening * Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at least 4 weeks before the start of study intervention Exclusion Criteria: * Has one of the following tumor locations/types: * NSCLC involving the superior sulcus * Large cell neuro-endocrine cancer (LCNEC) * Sarcomatoid tumor * Diagnosis of SCLC or, for mixed tumors, presence of small cell elements * 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 * Has uncontrolled, significant cardiovascular disease or cerebrovascular disease, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, uncontrolled symptomatic arrhythmia, prolongation of QT corrected for heart rate by Fridericia's cube root formula (QTcF) interval to \>480 ms, and/or other serious cardiovascular and cerebrovascular diseases within the 6 months preceding study intervention * Has received prior neoadjuvant therapy for their current NSCLC diagnosis * Has received prior systemic anticancer therapy including investigational agents within 4 weeks before the first dose of study intervention * Has received prior radiotherapy within 2 weeks of start of study intervention, or radiation-related toxicities, requiring corticosteroids * 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 an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration * Has a 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 the first dose of study medication * Has a known additional malignancy that is progressing or has required active treatment within the past 5 years * Has an active autoimmune disease that has required systemic treatment in the 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 * Is an HIV-infected participant with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease * Has a concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV deoxyribonucleic acid (DNA)) and Hepatitis C virus (defined as anti-HCV antibody (Ab) positive and detectable HCV ribonucleic acid (RNA)) infection * Has a history of allogeneic tissue/solid organ transplant * Has not adequately recovered from major surgery or have ongoing surgical complications * Severe hypersensitivity (≥Grade 3) to study intervention, any of its excipients, and/or to another biologic therapy

Study locations (49)

UAMS Winthrop P. Rockefeller Cancer Institute ( Site 0060)

Little Rock, Arkansas, 72205

Recruiting
Study Coordinator · Contact

Highlands Oncology Group-Research Department ( Site 0062)

Springdale, Arkansas, 72762

Recruiting
Study Coordinator · Contact

Beverly Hills Cancer Center ( Site 0070)

Beverly Hills, California, 90211

Recruiting
Study Coordinator · Contact

The Angeles Clinic and Research Institute ( Site 0040)

Los Angeles, California, 90025

Recruiting
Study Coordinator · Contact

The Angeles Clinic and Research Institute- A Cedars-Sinai Affiliate ( Site 0079)

Los Angeles, California, 90025

Recruiting
Study Coordinator · Contact

UCLA Clinical & Translational Research Center (CTRC) ( Site 0033)

Los Angeles, California, 90095

Recruiting
Study Coordinator · Contact

Hoag Memorial Hospital Presbyterian ( Site 0096)

Newport Beach, California, 92663

Recruiting
Study Coordinator · Contact

St. Joseph Hospital-The Center for Cancer Prevention and Treatment ( Site 4002)

Orange, California, 92868

Recruiting
Study Coordinator · Contact

San Francisco Oncology Associates ( Site 0066)

San Francisco, California, 94115

Recruiting
Study Coordinator · Contact

Stamford Hospital ( Site 0083)

Stamford, Connecticut, 06902

Recruiting
Study Coordinator · Contact

Mayo Clinic in Florida ( Site 0014)

Jacksonville, Florida, 32224

Recruiting
Study Coordinator · Contact

Mount Sinai Cancer Center ( Site 0038)

Miami Beach, Florida, 33140

Recruiting
Study Coordinator · Contact

Mid Florida Hematology and Oncology Center ( Site 0018)

Orange City, Florida, 32763

Recruiting
Study Coordinator · Contact

Emory University School of Medicine-Phase I ( Site 0056)

Atlanta, Georgia, 30322

Recruiting
Study Coordinator · Contact

Northside Hospital ( Site 0055)

Atlanta, Georgia, 30342

Recruiting
Study Coordinator · Contact

Centricity Research Columbus Cancer Center ( Site 0005)

Columbus, Georgia, 31904

Completed

Southeastern Regional Medical Center ( Site 0065)

Newnan, Georgia, 30265

Recruiting
Study Coordinator · Contact

Lewis Cancer and Research Pavilion ( Site 0063)

Savannah, Georgia, 31405

Recruiting
Study Coordinator · Contact

Archbold Cancer Center ( Site 0071)

Thomasville, Georgia, 31792

Recruiting
Study Coordinator · Contact

Edward-Elmhurst Healthcare, Elmhurst Hospital-Nancy W. Knowles Cancer Center ( Site 0017)

Elmhurst, Illinois, 60126

Completed

Accellacare of Duly ( Site 4005)

Lisle, Illinois, 60532

Recruiting
Study Coordinator · Contact

Edward-Elmhurst Healthcare, Edward Hospital-Edward Cancer Center ( Site 0078)

Naperville, Illinois, 60540

Completed

Parkview Research Center at Parkview Regional Medical Center ( Site 0089)

Fort Wayne, Indiana, 46845

Recruiting
Study Coordinator · Contact

Indiana University Health Arnett Cancer Center ( Site 0076)

Lafayette, Indiana, 47904

Recruiting
Study Coordinator · Contact

Saint Elizabeth Medical Center Edgewood-Cancer Care Center ( Site 0061)

Edgewood, Kentucky, 41017

Recruiting
Study Coordinator · Contact

LSU Health Baton Rouge North Clinic ( Site 4003)

Baton Rouge, Louisiana, 70805

Recruiting
Study Coordinator · Contact

Our Lady of the Lake Physician Group-Medical Oncology ( Site 0080)

Baton Rouge, Louisiana, 70808

Recruiting
Study Coordinator · Contact

New England Cancer Specialists ( Site 0095)

Westbrook, Maine, 04092

Recruiting
Study Coordinator · Contact

Allina Health Cancer Institute - Abbott Northwestern Hospital ( Site 0027)

Minneapolis, Minnesota, 55407

Recruiting
Study Coordinator · Contact

Mayo Clinic - Rochester ( Site 0073)

Rochester, Minnesota, 55905

Recruiting
Study Coordinator · Contact

Mercy South - David M Sindelar Cancer Center ( Site 0098)

St Louis, Missouri, 63128

Recruiting
Study Coordinator · Contact

Mercy Research - David C. Pratt Cancer Center ( Site 0006)

St Louis, Missouri, 63141

Recruiting
Study Coordinator · Contact

Renown Regional Medical Center-Renown Health Medical Oncology ( Site 0037)

Reno, Nevada, 89502

Recruiting
Study Coordinator · Contact

Atlantic Health Morristown Medical Center ( Site 0077)

Morristown, New Jersey, 07960

Recruiting
Study Coordinator · Contact

Cayuga Medical Center ( Site 0086)

Ithaca, New York, 14850

Recruiting
Study Coordinator · Contact

Stony Brook University-Cancer Center ( Site 0054)

Stony Brook, New York, 11794

Recruiting
Study Coordinator · Contact

White Plains Hospital ( Site 0091)

White Plains, New York, 10601

Recruiting
Study Coordinator · Contact

Sanford Fargo Medical Center-Roger Maris Cancer Center ( Site 0057)

Fargo, North Dakota, 58102

Recruiting
Study Coordinator · Contact

Hightower Clinical, LLC ( Site 0084)

Oklahoma City, Oklahoma, 73102

Recruiting
Study Coordinator · Contact

Oregon Health and Science University ( Site 0052)

Portland, Oregon, 97239

Recruiting
Study Coordinator · Contact

Penn State Milton S. Hershey Medical Center-Penn State Cancer Institute ( Site 0059)

Hershey, Pennsylvania, 17033

Recruiting
Study Coordinator · Contact

Lancaster General Hospital - Ann B Barshinger Cancer Institute ( Site 0068)

Lancaster, Pennsylvania, 17601

Recruiting
Study Coordinator · Contact

Saint Joseph's Candler Health System ( Site 4010)

Bluffton, South Carolina, 29910

Recruiting
Study Coordinator · Contact

Medical University of South Carolina-Hollings Cancer Center ( Site 0045)

Charleston, South Carolina, 29425

Recruiting
Study Coordinator · Contact

Sanford Cancer Center ( Site 0053)

Sioux Falls, South Dakota, 57104

Recruiting
Study Coordinator · Contact

Avera Cancer Institute- Research ( Site 0090)

Sioux Falls, South Dakota, 57105

Recruiting
Study Coordinator · Contact

University of Tennessee Medical Center Knoxville ( Site 0082)

Knoxville, Tennessee, 37920

Recruiting
Study Coordinator · Contact

Millennium Research & Clinical Development ( Site 0039)

Houston, Texas, 77090

Completed

Huntsman Cancer Institute ( Site 0042)

Salt Lake City, Utah, 84112-5500

Recruiting
Study Coordinator · Contact