Recruiting

Phase 3

Pembrolizumab & Sac-TMTPembrolizumab With or Without Maintenance Sacituzumab Tirumotecan (Sac-TMT; MK-2870) in Metastatic Squamous Non-small Cell Lung Cancer (NSCLC) [MK-2870-023]

Sponsor:

Merck Sharp & Dohme LLC

Code:

NCT06422143

Conditions

Non-small Cell Lung Cancer

NSCLC

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Pembrolizumab

sac-TMT

Carboplatin

Paclitaxel

Nab-paclitaxel

Study Details

Brief summary:

This is a phase 3 study of pembrolizumab in combination with carboplatin/taxane (paclitaxel or nab-paclitaxel) followed by pembrolizumab with or without maintenance sacituzumab tirumotecan (sac-TMT; MK-2870) in first-line treatment of metastatic squamous non-small cell lung cancer. It is hypothesized that pembrolizumab with maintenance sacituzumab tirumotecan is superior to pembrolizumab without sacituzumab tirumotecan maintenance with respect to overall survival (OS).

Conditions

Non-small Cell Lung Cancer

NSCLC

Study ID

NCT06422143

Start date

Jun 10, 2024

Status verified date

Sep, 2026

Completion date

Aug 15, 2031

Anticipated

Primary completion date

Jan 12, 2029

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

Histologically or cytologically confirmed diagnosis of squamous non-small cell lung cancer (NSCLC) \[Stage IV: M1a, M1b, M1c, American Joint Committee on Cancer Staging Manual, version 8\]
Measurable disease per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 as assessed by the local site investigator/radiology
Has life expectancy ≥3 months
Has Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1 assessed within 7 days prior to allocation
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 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 before allocation
Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening
Participants who have adverse events (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)
Has adequate organ function
For Maintenance only (prior to randomization): is without disease progression of their NSCLC, as determined by BICR using RECIST 1.1 after completion of study-specified Induction with an evaluable scan at Week 12 or most recent scan before randomization
For Maintenance only (prior to randomization): has ECOG PS of 0 or 1 as assessed at the Prerandomization Visit
For Maintenance only (prior to randomization): all AEs (with the exception of alopecia, Grade ≤2 fatigue, Grade ≤2 peripheral neuropathy, and Grade ≤2 endocrine-related AEs requiring treatment or hormone replacement) have recovered
For Maintenance only (prior to randomization): has not experienced a pneumonitis/interstitial lung disease (ILD) event during the study-specified induction

Exclusion Criteria:

Diagnosis of small cell lung cancer or, for mixed tumors, presence of small cell elements
History of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing
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 including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, uncontrolled symptomatic arrhythmia, prolongation of QTcF interval to >480 ms, and other serious cardiovascular and cerebrovascular diseases within 6 months before study intervention
HIV-infected participants who have been newly diagnosed or with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
Received prior systemic chemotherapy or other targeted or biological antineoplastic therapy for their metastatic NSCLC. Note: Prior treatment with chemotherapy and/or radiation as a part of neoadjuvant or adjuvant therapy or chemoradiation therapy for nonmetastatic NSCLC is allowed as long as therapy was completed at least 12 months before diagnosis of metastatic NSCLC
Received prior therapy with an anti-programmed cell death 1 protein (PD-1), anti-programmed cell death ligand 1 (PD-L1), or anti programmed cell death ligand 2 (PD-L2) agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, cytotoxic T lymphocyte-associated protein 4, OX-40, CD137). Note: Prior treatment with an anti-PD-1 or anti-PD-L1 agent for nonmetastatic NSCLC is allowed as long as therapy was completed at least 12 months before diagnosis of metastatic NSCLC
Received prior treatment with a trophoblast cell-surface antigen 2 (TROP2)-targeted antidrug conjugate (ADC)
Received radiation therapy to the lung that is >30 Gray within 6 months of start of study intervention
Received prior radiotherapy within 2 weeks of start of study intervention, or radiation-related toxicities, requiring corticosteroids
Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
Participants who have not adequately recovered from major surgery or have ongoing surgical complications
Received prior treatment with a topoisomerase I inhibitor-containing ADC
Is currently receiving a strong inducer/inhibitor of CYP3A4 that cannot be discontinued for the duration of the study (the required washout period before starting sac-TMT is 2 weeks)
Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
Has known central nervous system (CNS) metastases/carcinomatous meningitis
Severe hypersensitivity (≥Grade 3) to study intervention and/or any of its excipients or to another biologic therapy
Active autoimmune disease that has required systemic treatment in the past 2 years (replacement therapy \[eg, thyroxine, insulin, or physiologic corticosteroid\] is allowed)
Has a history of (noninfectious)pneumonitis/ILD that required steroids, has current pneumonitis/ILD, or has suspected ILD or pneumonitis that cannot be ruled out by standard diagnostic assessments at Screening
Active infection requiring systemic therapy
History of allogeneic tissue/solid organ transplant

Study Design

Enrollment

851 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Maintenance Arm A: Pembrolizumab + sac-TMT

During the Induction phase, participants receive pembrolizumab 200 mg q3w for 4 cycles, carboplatin area under the curve (AUC) 6 (mg/mL/min) q3w for 4 cycles, and paclitaxel 200 mg/m2 q3w for 4 cycles or nab-paclitaxel 100 mg/m2 weekly for 4 cycles. Note: per investigator discretion, carboplatin AUC 5 mg/mL/min q3w or paclitaxel 175mg/m2 q3w may be administered.

During the Maintenance phase, participants receive sac-TMT 4 mg/kg infusion every 2 weeks (q2w) until discontinuation criteria is met for sac-TMT; and pembrolizumab 400 mg every 6 weeks (q6w) for 96 weeks.

active comparator: Maintenance Arm B: Pembrolizumab Monotherapy

During the Induction phase, participants receive pembrolizumab 200 mg q3w for 4 cycles, carboplatin AUC 6 (mg/mL/min) q3w for 4 cycles, and paclitaxel 200 mg/m2 q3w for 4 cycles or nab-paclitaxel 100 mg/m2 weekly for 4 cycles.

During the Maintenance phase, participants receive pembrolizumab 400 mg q6w for 96 weeks.

Interventions

Pembrolizumab

Intravenous (IV) infusion

sac-TMT

IV infusion

Carboplatin

Participants receive AUC 6 or AUC 5 mg/mL/min IV infusion on Day 1 of each 21-day cycle for 4 cycles as background therapy during the study.

Paclitaxel

Participants receive 200 mg/m\^2 or 175 mg/m\^2 IV infusion on Day 1 of each 21-day cycle for 4 cycles as background therapy during the study.

Nab-paclitaxel

Participants receive 100 mg/m\^2 IV infusion on Days 1, 8 and 15 of each 21-day cycle for 4 cycles as background therapy during the study.

Primary outcome measure

Overall survival (OS) [ Time Frame: Up to ~50 months ]

Central Contacts and Locations

Central contacts

Toll Free Number

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

Locations

CARTI Cancer Center ( Site 0006)

Recruiting

Little Rock, Arkansas, United States, 72205

Contacts

Study Coordinator

501-906-3000

Roy and Patricia Disney Family Cancer Center - Providence Saint Joseph Medical Center ( Site 0122)

Recruiting

Burbank, California, United States, 91505

Contacts

Study Coordinator

818-748-4723

Sharp Memorial Hospital ( Site 9544)

Recruiting

San Diego, California, United States, 92123

Contacts

Study Coordinator

858-939-7201

Intermountain Health Cancer Center Lutheran Hospital ( Site 0119)

Recruiting

Golden, Colorado, United States, 80401

Contacts

Study Coordinator

303-403-6381

Intermountain Health St. Mary's Regional Hospital ( Site 0116)

Recruiting

Grand Junction, Colorado, United States, 81501

Contacts

Study Coordinator

970-298-6576

Washington Hospital Center ( Site 0037)

Recruiting

Washington D.C., District of Columbia, United States, 20010

Contacts

Study Coordinator

202-877-8839

University of Chicago Medical Center ( Site 0145)

Recruiting

Chicago, Illinois, United States, 60637

Contacts

Study Coordinator

773-352-1745

Trinity Health Saint Joseph Mercy Hospital Ann Arbor ( Site 9552)

Recruiting

Ypsilanti, Michigan, United States, 48197

Contacts

Study Coordinator

734-712-4950

Allina Health Cancer Institute - Abbott Northwestern Hospital ( Site 0146)

Recruiting

Minneapolis, Minnesota, United States, 55407

Contacts

Study Coordinator

888-425-5462

John Theurer Cancer Center at Hackensack University Medical Center ( Site 0035)

Recruiting

Hackensack, New Jersey, United States, 07601

Contacts

Study Coordinator

551-996-5900

Capital Health Medical Center - Hopewell ( Site 0034)

Recruiting

Pennington, New Jersey, United States, 08534

Contacts

Study Coordinator

609-303-4733

University of New Mexico Comprehensive Cancer Center ( Site 0135)

Recruiting

Albuquerque, New Mexico, United States, 87131

Contacts

Study Coordinator

505-272-4946

St Luke's University Health Network ( Site 0017)

Recruiting

Bethlehem, Pennsylvania, United States, 18015

Contacts

Study Coordinator

484-658-1792

Thomas Jefferson University - Clinical Research Institute ( Site 0147)

Recruiting

Philadelphia, Pennsylvania, United States, 19107

Contacts

Study Coordinator

215-955-8874

Memorial Hermann Cancer Center ( Site 0015)

Recruiting

Houston, Texas, United States, 77030

Contacts

Study Coordinator

281-540-7905

Oncology Consultants P.A. ( Site 0124)

Recruiting

Houston, Texas, United States, 77030

Contacts

Study Coordinator

713-600-0913

Kingston Health Sciences Centre-Kingston General Hospital Site ( Site 0100)

Recruiting

Kingston, Ontario, Canada, K7L 2V7

Contacts

Study Coordinator

613-549-6666

Waterloo Regional Health Network (WRHN) ( Site 0153)

Recruiting

Kitchener, Ontario, Canada, N2G 1G3

Contacts

Study Coordinator

519749430

St. Marys Hospital Center ( Site 0105)

Recruiting

Montreal, Quebec, Canada, H3T 1M5

Contacts

Study Coordinator

514-345-3511

McGill University Health Centre ( Site 0103)

Recruiting

Montreal, Quebec, Canada, H4A 3J1

Contacts

Study Coordinator

514 934-1934

Centre integre universitaire de sante et de services sociaux de la Mauricie-et-du-centre-du-quebec ( Site 0106)

Recruiting

Trois-Rivières, Quebec, Canada, G8Z 3R9

Contacts

Study Coordinator

819-697-3333

More Information

Sponsor

Merck Sharp & Dohme LLC

Last update posted

Sep 3, 2026

Last verified

Sep, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Merck Sharp & Dohme LLC on 2026-09-03.