Recruiting
Phase 3

Pembrolizumab & Sacituzumab Tirxumotecan

Sponsor:

Merck Sharp & Dohme LLC

Code:

NCT06312137

Conditions

Non Small Cell Lung Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Sacituzumab tirumotecan

Pembrolizumab

Cisplatin

Pemetrexed

Gemcitabine

Study Details

Brief 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).

Conditions

Non Small Cell Lung Cancer

Study ID

NCT06312137

Start date

Apr 3, 2024

Status verified date

Aug, 2026

Completion date

Oct 23, 2034

Anticipated

Primary completion date

Feb 21, 2034

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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) interstitial lung disease (ILD)/pneumonitis, has current ILD/pneumonitis, or has suspected ILD or pneumonitis that cannot be ruled out by standard diagnostic assessments at screening
  • 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 Design

Enrollment

780 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Pembrolizumab + Sacituzumab tirumotecan

Participants will receive pembrolizumab 200 mg intravenous (IV) infusion every 3 weeks (Q3W) for up to 12 weeks + double-platinum chemotherapy per neoplasm histology classification at the investigator's discretion as neoadjuvant therapy prior to surgery; followed by sacituzumab tirumotecan 4 mg/kg IV infusion every 2 weeks (Q2W) for up to 12 doses (\~24 weeks) with pembrolizumab monotherapy 200 mg IV infusion every 6 weeks (Q6W) for up to 7 cycles (\~42 weeks).

active comparator: Pembrolizumab

Participants will receive pembrolizumab 200 mg intravenous (IV) infusion Q3W for up to 12 weeks + double-platinum chemotherapy per neoplasm histology classification at the investigator's discretion as neoadjuvant therapy prior to surgery; followed by pembrolizumab monotherapy 200 mg IV infusion Q6W for up to 7 cycles (\~42 weeks).

Interventions

Sacituzumab tirumotecan

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

Pembrolizumab

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

Cisplatin

Cisplatin is administered as 75 mg/m\^2 IV infusion q3w for up to 12 weeks as background treatment in neoadjuvant phase

Pemetrexed

Pemetrexed will be administered in the neoadjuvant phase as 500 mg/m\^2 IV infusion q3w for up to 12 weeks as background treatment in participants with nonsquamous NSCLC.

Gemcitabine

Gemcitabine will be administered in the neoadjuvant phase as 1000 mg/m\^2 or 1250 mg/m\^2 IV infusion on day 1 and day 8 q3w for up to 24 weeks as background treatment in participants with squamous NSCLC.

Carboplatin

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.

Paclitaxel

Paclitaxel will be administered in the neoadjuvant phase as 175 mg/m\^2 or 200 mg/m\^2 IV infusion q3w for up to 12 weeks as background treatment.

Rescue medication

Participants are permitted to take rescue medications to prevent hypersensitivity and/or infusion reactions as a premedication to study treatment. Rescue medications include antihistamine, H2 receptor antagonist, acetaminophen or equivalent, dexamethasone or equivalent, and granulocyte colony-stimulating factor. A steroid mouthwash (dexamethasone or equivalent) may be given as prophylaxis for stomatitis/oral mucositis.

Primary outcome measure

  • Disease-free survival (DFS) as assessed by Blinded Independent Central Review (BICR) [ Time Frame: Up to ~ 93 months ]

Central Contacts and Locations

Central contacts

Toll Free Number

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

Locations

UAMS Winthrop P. Rockefeller Cancer Institute ( Site 0060)

Recruiting

Little Rock, Arkansas, United States, 72205

Contacts

Study Coordinator

601-278-6499

Highlands Oncology Group-Research Department ( Site 0062)

Recruiting

Springdale, Arkansas, United States, 72762

Contacts

Study Coordinator

479-334-2562

Beverly Hills Cancer Center ( Site 0070)

Recruiting

Beverly Hills, California, United States, 90211

Contacts

Study Coordinator

310-432-8933

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

Recruiting

Los Angeles, California, United States, 90095

Contacts

Study Coordinator

424-325-9070

Hoag Memorial Hospital Presbyterian ( Site 0096)

Recruiting

Newport Beach, California, United States, 92663

Contacts

Study Coordinator

949-764-4060

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

Recruiting

Orange, California, United States, 92868

Contacts

Study Coordinator

714-734-6220

San Francisco Oncology Associates ( Site 0066)

Recruiting

San Francisco, California, United States, 94115

Contacts

Study Coordinator

415-600-1102

Stamford Hospital ( Site 0083)

Recruiting

Stamford, Connecticut, United States, 06902

Contacts

Study Coordinator

203-358-8879

Mayo Clinic in Florida ( Site 0014)

Recruiting

Jacksonville, Florida, United States, 32224

Contacts

Study Coordinator

904-953-3570

Mount Sinai Cancer Center ( Site 0038)

Recruiting

Miami Beach, Florida, United States, 33140

Contacts

Study Coordinator

305-674-2625

Mid Florida Hematology and Oncology Center ( Site 0018)

Recruiting

Orange City, Florida, United States, 32763

Contacts

Study Coordinator

386-960-7070

Piedmont Atlanta Hospital ( Site 4000)

Recruiting

Atlanta, Georgia, United States, 30309

Contacts

Study Coordinator

404-425-1777

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

Recruiting

Atlanta, Georgia, United States, 30322

Contacts

Study Coordinator

404-778-1900

Northside Hospital ( Site 0055)

Recruiting

Atlanta, Georgia, United States, 30342

Contacts

Study Coordinator

404-851-8000

Southeastern Regional Medical Center ( Site 0065)

Recruiting

Newnan, Georgia, United States, 30265

Contacts

Study Coordinator

770-400-6000

Lewis Cancer and Research Pavilion ( Site 0063)

Recruiting

Savannah, Georgia, United States, 31405

Contacts

Study Coordinator

912-819-5704

Archbold Cancer Center ( Site 0071)

Recruiting

Thomasville, Georgia, United States, 31792

Contacts

Study Coordinator

229-584-5417

Accellacare of Duly ( Site 4005)

Recruiting

Lisle, Illinois, United States, 60532

Contacts

Study Coordinator

630-545-7760

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

Recruiting

Fort Wayne, Indiana, United States, 46845

Contacts

Study Coordinator

260-266-6626

Indiana University Health Arnett Cancer Center ( Site 0076)

Recruiting

Lafayette, Indiana, United States, 47904

Contacts

Study Coordinator

765-838-6885

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

Recruiting

Edgewood, Kentucky, United States, 41017

Contacts

Study Coordinator

859-301-4736

LSU Health Baton Rouge North Clinic ( Site 4003)

Recruiting

Baton Rouge, Louisiana, United States, 70805

Contacts

Study Coordinator

225-765-7956

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

Recruiting

Baton Rouge, Louisiana, United States, 70808

Contacts

Study Coordinator

225-765-7956

New England Cancer Specialists ( Site 0095)

Recruiting

Westbrook, Maine, United States, 04092

Contacts

Study Coordinator

207-303-3300

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

Recruiting

Minneapolis, Minnesota, United States, 55407

Contacts

Study Coordinator

888-425-5462

Mayo Clinic - Rochester ( Site 0073)

Recruiting

Rochester, Minnesota, United States, 55905

Contacts

Study Coordinator

904-953-1050

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

Recruiting

St Louis, Missouri, United States, 63128

Contacts

Study Coordinator

314-525-4928

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

Recruiting

St Louis, Missouri, United States, 63141

Contacts

Study Coordinator

314-251-4400

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

Recruiting

Reno, Nevada, United States, 89502

Contacts

Study Coordinator

775-982-5050

Atlantic Health Morristown Medical Center ( Site 0077)

Recruiting

Morristown, New Jersey, United States, 07960

Contacts

Study Coordinator

973-971-7000

Cayuga Medical Center ( Site 0086)

Recruiting

Ithaca, New York, United States, 14850

Contacts

Study Coordinator

607-277-4341

University Hospital at Stony Brook ( Site 0054)

Recruiting

Stony Brook, New York, United States, 11794

Contacts

Study Coordinator

631-372-7212

White Plains Hospital ( Site 0091)

Recruiting

White Plains, New York, United States, 10601

Contacts

Study Coordinator

914-681-0600

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

Recruiting

Fargo, North Dakota, United States, 58102

Contacts

Study Coordinator

701-234-6161

Hightower Clinical, LLC ( Site 0084)

Recruiting

Oklahoma City, Oklahoma, United States, 73102

Contacts

Study Coordinator

405-479-8331

Oregon Health and Science University ( Site 0052)

Recruiting

Portland, Oregon, United States, 97239

Contacts

Study Coordinator

503-494-0283

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

Recruiting

Hershey, Pennsylvania, United States, 17033

Contacts

Study Coordinator

717-531-0003

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

Recruiting

Lancaster, Pennsylvania, United States, 17601

Contacts

Study Coordinator

717-544-0511

Saint Joseph's Candler Health System ( Site 4010)

Recruiting

Bluffton, South Carolina, United States, 29910

Contacts

Study Coordinator

912-819-5704

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

Recruiting

Charleston, South Carolina, United States, 29425

Contacts

Study Coordinator

843-792-4271

Sanford Cancer Center ( Site 0053)

Recruiting

Sioux Falls, South Dakota, United States, 57104

Contacts

Study Coordinator

605-328-8800

Avera Cancer Institute- Research ( Site 0090)

Recruiting

Sioux Falls, South Dakota, United States, 57105

Contacts

Study Coordinator

605-322-3295

University of Tennessee Medical Center Knoxville ( Site 0082)

Recruiting

Knoxville, Tennessee, United States, 37920

Contacts

Study Coordinator

865-305-9000

Huntsman Cancer Institute ( Site 0042)

Recruiting

Salt Lake City, Utah, United States, 84112-5500

Contacts

Study Coordinator

801-587-7000

Centre Intégré de Santé et de Services Sociaux de la Montérégie-Centre ( Site 0100)

Recruiting

Greenfield Park, Quebec, Canada, J4V 2H1

Contacts

Study Coordinator

450-466-5000#3226

Centre Hospitalier de l'Université de Montréal ( Site 0104)

Recruiting

Montreal, Quebec, Canada, H2X 3E4

Contacts

Study Coordinator

5148908000x26214

St. Marys Hospital Center ( Site 0107)

Recruiting

Montreal, Quebec, Canada, H3T 1M5

Contacts

Study Coordinator

514-345-3511

McGill University Health Centre ( Site 0105)

Recruiting

Montreal, Quebec, Canada, H4A 3J1

Contacts

Study Coordinator

5149341934X36675

More Information

Sponsor

Merck Sharp & Dohme LLC

Last update posted

Aug 21, 2026

Last verified

Aug, 2026

Keywords

  • Carcinoma
  • Lung cancer
  • Non-small cell lung cancer

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-11. This information was provided to ClinicalTrials.gov by Merck Sharp & Dohme LLC on 2026-08-21.