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RecruitingInterventionalPhase 2

KEYMAKER-U01 Substudy 01E: A Phase 2 Umbrella Study With Rolling Arms of Investigational Agents With or Without Chemotherapy in Combination With Pembrolizumab in Treatment of Participants With Newly Diagnosed Resectable Stages II-IIIB (N2) Non-small Cell Lung Cancer (NSCLC)

NCT ID: NCT06788912Sponsor: Merck Sharp & Dohme LLCLast updated: 2026-06-01

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.

Arms & interventions

  • BiologicalPembrolizumab (neoadjuvant)

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

  • DrugCisplatin

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

  • DrugGemcitabine

    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.

  • DrugPemetrexed

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

  • DrugSacituzumab tirumotecan

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

  • DrugH1 receptor antagonist

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

  • DrugH2 receptor antagonist

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

  • DrugAcetaminophen (or equivalent)

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

  • DrugDexamethasone (or equivalent)

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

  • DrugCarboplatin

    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

  • BiologicalPembrolizumab (adjuvant)

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

  • DrugPaclitaxel

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

  • DrugSteroid mouthwash (dexamethasone or equivalent)

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

Outcome measures

Primary

  • 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.

    Time frame: 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.)

    Time frame: Up to approximately 20 weeks

Secondary

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

    Time frame: Up to approximately 5 years

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

    Time frame: Up to approximately 1 year

  • Event-free Survival (EFS)

    Time frame: Up to approximately 5 years

  • Overall Survival (OS)

    Time frame: Up to approximately 5 years

  • Distant Metastasis-Free Survival (DMFS)

    Time frame: Up to approximately 5 years

  • Objective Response Rate (ORR)

    Time frame: Up to approximately 12 weeks

  • Percentage of Participants Who Experience a Perioperative Complication

    Time frame: Up to approximately 20 weeks

  • Mean Length of Hospital Stay

    Time frame: Up to approximately 20 weeks

  • Percentage of Participants Who Require Hospital Readmission after Discharge

    Time frame: Up to approximately 20 weeks

  • Mean Length of Surgery

    Time frame: Up to approximately 20 weeks

  • Percentage of Participants Who Require a Blood Transfusion

    Time frame: Up to approximately 20 weeks

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
The main inclusion and exclusion criteria include but are not limited to the following: Inclusion Criteria: * 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. Exclusion Criteria: * 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. * Active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid) is allowed. * History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease. * Active infection requiring systemic therapy. * Hepatitis B (defined as hepatitis B surface antigen \[HBsAg\] reactive) or Hepatitis C virus (defined as detectable hepatitis C virus (HCV) ribonucleic acid (RNA) \[qualitative\]) infection. * Known history of human immunodeficiency virus (HIV) infection. * History of allogeneic tissue/solid organ transplant.

Study locations (8)

Southern Cancer Center (SCC) ( Site 8004)

Daphne, Alabama, 36526

Recruiting
Study Coordinator · Contact

Sansum Clinic (Ridley Tree) ( Site 8012)

Santa Barbara, California, 93105

Recruiting
Study Coordinator · Contact

Rocky Mountain Cancer Centers (RMCC) ( Site 8011)

Lone Tree, Colorado, 80124

Recruiting
Study Coordinator · Contact

MedStar Franklin Square Medical Center ( Site 0033)

Baltimore, Maryland, 21237

Recruiting
Study Coordinator · Contact

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

Eugene, Oregon, 97401

Recruiting
Study Coordinator · Contact

Texas Oncology - Central/South Texas ( Site 8009)

Austin, Texas, 78705

Recruiting
Study Coordinator · Contact

Texas Oncology - Northeast Texas ( Site 8005)

Tyler, Texas, 75702

Recruiting
Study Coordinator · Contact

Virginia Cancer Specialists (VCS) ( Site 8002)

Fairfax, Virginia, 22031

Recruiting
Study Coordinator · Contact