Sacituzumab Tirumotecan (MK-2870) Versus Pemetrexed and Carboplatin Combination Therapy in Participants With Epidermal Growth Factor (EGFR)-Mutated, Advanced Nonsquamous Non-small Cell Lung Cancer (NSCLC) Who Have Progressed on Prior EGFR Tyrosine Kinase Inhibitors (MK-2870-009)

June 5, 2026 updated by: Merck Sharp & Dohme LLC

A Randomized, Open-label, Phase 3 Study of MK-2870 vs. Platinum Doublets in Participants With EGFR-mutated, Advanced Nonsquamous Non-small Cell Lung Cancer (NSCLC) Who Have Progressed on Prior EGFR Tyrosine Kinase Inhibitors

The purpose of this study is to evaluate sacituzumab tirumotecan versus pemetrexed in combination with carboplatin for the treatment of epidermal growth factor receptor (EGFR)-mutated advanced non-squamous non-small cell lung cancer (NSCLC). Participants in this study have NSCLC that has continued to progress on prior treatment with EGFR tyrosine kinase inhibitors (TKIs).

The primary hypotheses of this study is that sacituzumab tirumotecan is better than platinum-based doublet chemotherapy (pemetrexed and carboplatin) in regard to overall survival (OS).

Study Overview

Status

Active, not recruiting

Conditions

Non-small Cell Lung Cancer (NSCLC)

Intervention / Treatment

Detailed Description

Participants will be randomized 1:1 into two arms:

Sacituzumab tirumotecan
Pemetrexed plus Carboplatin

Participants will receive treatment until any of the criteria for discontinuation of study intervention are met.

Study Type

Interventional

Enrollment (Estimated)

520

Phase

Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Argentina
- - La Rioja, Argentina, F5300COE
    - Fundación CORI para la Investigación y Prevención del Cáncer ( Site 0303)
- Buenos Aires
  - Caba., Buenos Aires, Argentina, C1430EGF
    - Clinica Adventista Belgrano-Oncology ( Site 0315)
  - Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina, C1426ANZ
    - Instituto Alexander Fleming ( Site 0307)
- Buenos Aires F.D.
  - Buenos Aires, Buenos Aires F.D., Argentina, C1280AEB
    - Hospital Británico de Buenos Aires-Oncology ( Site 0304)
- Córdoba Province
  - Río Cuarto, Córdoba Province, Argentina, X5800ALB
    - Centro Privado de RMI Río Cuarto S.A. II ( Site 0310)
- Santa Fe Province
  - Rosario, Santa Fe Province, Argentina, S2000KZE
    - Instituto de Oncología de Rosario ( Site 0301)
Canada
- Alberta
  - Edmonton, Alberta, Canada, T6G 1Z2
    - Cross Cancer Institute ( Site 0201)
- Ontario
  - Kitchener, Ontario, Canada, N2G 1G3
    - Waterloo Regional Health Network (WRHN) ( Site 0207)
  - Toronto, Ontario, Canada, M5G 2M9
    - Princess Margaret Cancer Centre ( Site 0203)
- Quebec
  - Montreal, Quebec, Canada, H4A 3J1
    - McGill University Health Centre ( Site 0204)
China
- Anhui
  - Hefei, Anhui, China, 230031
    - Anhui Provincial Cancer Hospital ( Site 3132)
- Beijing Municipality
  - Beijing, Beijing Municipality, China, 100142
    - Beijing Cancer hospital ( Site 3100)
  - Beijing, Beijing Municipality, China, 100730
    - Beijing Peking Union Medical College Hospital-pneumology department ( Site 3107)
- Chongqing Municipality
  - Chongqing, Chongqing Municipality, China, 400030
    - Chongqing University Cancer Hospital-Medical Oncology ( Site 3128)
- Fujian
  - Fuzhou, Fujian, China, 350014
    - Fujian Cancer Hospital ( Site 3124)
  - Xiamen, Fujian, China, 361003
    - The First Affiliated hospital of Xiamen University ( Site 3125)
- Guangdong
  - Guangzhou, Guangdong, China, 510515
    - Southern Medical University Nanfang Hospital-Depatrment of Respiratory and Critical Care Medicine ( Site 3102)
- Guangxi
  - Nanning, Guangxi, China, 530021
    - Guangxi Medical University Affiliated Tumor Hospital-Respiratory Oncology ( Site 3103)
- Heilongjiang
  - Harbin, Heilongjiang, China, 150081
    - Harbin Medical University Cancer Hospital ( Site 3109)
- Henan
  - Zhengzhou, Henan, China, 450008
    - Henan Cancer Hospital ( Site 3105)
- Hubei
  - Wuhan, Hubei, China, 430000
    - Tongji Hospital Tongji Medical,Science & Technology ( Site 3121)
  - Wuhan, Hubei, China, 430079
    - Hubei Cancer Hospital ( Site 3122)
- Hunan
  - Changsha, Hunan, China, 410011
    - The Second Xiangya Hospital of Central South University-Oncology ( Site 3104)
- Jiangsu
  - Nanjing, Jiangsu, China, 210031
    - Nanjing Drum Tower Hospital JiangBei International Branch Hospital ( Site 3117)
  - Suzhou, Jiangsu, China, 215006
    - The First Affiliated Hospital of Soochow University-Respiratory Department ( Site 3118)
- Jiangxi
  - Nanchang, Jiangxi, China, 330006
    - The Second Affiliated Hospital of Nanchang University ( Site 3119)
- Shaanxi
  - Xi'an, Shaanxi, China, 710004
    - The Second Affiliated Hospital of Xi'an Jiaotong University ( Site 3130)
- Shandong
  - Jinan, Shandong, China, 250013
    - Jinan Central Hospital ( Site 3113)
  - Jinan, Shandong, China, 250117
    - Shandong Cancer Hospital ( Site 3112)
- Shanghai Municipality
  - Shanghai, Shanghai Municipality, China, 200032
    - Zhongshan Hospital of Fudan University ( Site 3133)
- Shanxi
  - Taiyuan, Shanxi, China, 410013
    - Shanxi Cancer Hospital ( Site 3114)
- Sichuan
  - Chengdu, Sichuan, China, 610041
    - West China Hospital, Sichuan University ( Site 3126)
  - Chengdu, Sichuan, China, 610042
    - Sichuan Cancer hospital. ( Site 3127)
- Zhejiang
  - Hangzhou, Zhejiang, China, 310006
    - The first Affiliated Hospital, Zhejiang University School of Medicine ( Site 3101)
  - Hangzhou, Zhejiang, China, 310016
    - Sir Run Run Shaw Hospital of Zhejiang University School of Medicine-Medical Oncology ( Site 3106)
  - Wenzhou, Zhejiang, China, 325015
    - The First Affiliated Hospital of Wenzhou Medical University-Respiratory department ( Site 3120)
Colombia
- Bogota D.C.
  - Bogotá, Bogota D.C., Colombia, 110131
    - FUNDACION CTIC CENTRO DE TRATAMIENTO E INVESTIGACION SOBRE CANCER LUIS CARLOS SARMIENTO ANGULO ( Site 0600)
  - Bogotá, Bogota D.C., Colombia, 111321
    - Clinica Colsanitas S.A, Sede Clínica Universitaria Colombia-Center Investigator ( Site 0606)
- Cesar Department
  - Valledupar, Cesar Department, Colombia, 200002
    - Sociedad de Oncología Y Hematología del Cesar S.A.S. ( Site 0601)
- Departamento de Córdoba
  - Montería, Departamento de Córdoba, Colombia, 230002
    - IMAT S.A.S ( Site 0602)
- Risaralda Department
  - Pereira, Risaralda Department, Colombia, 660001
    - Oncologos del Occidente ( Site 0604)
- Valle del Cauca Department
  - Cali, Valle del Cauca Department, Colombia, 760032
    - Fundacion Valle del Lili- CIC-Oncology CIC ( Site 0605)
France
- - Paris, France, 75014
    - Hopitaux Universitaires Paris Centre-Hopital Cochin-Unité d'Oncologie Thoracique ( Site 1304)
- Alsace
  - Strasbourg, Alsace, France, 67091
    - Nouvel Hôpital Civil (NHC) ( Site 1302)
- Bouches-du-Rhone
  - Marseille, Bouches-du-Rhone, France, 13009
    - Clinique Clairval ( Site 1306)
- Île-de-France Region
  - Villejuif, Île-de-France Region, France, 94805
    - Gustave Roussy ( Site 1303)
India
- Haryana
  - Gurugram, Haryana, India, 122001
    - Artemis hospital ( Site 3307)
- Maharashtra
  - Mumbai, Maharashtra, India, 400012
    - Tata Memorial Hospital-Medical Oncology ( Site 3304)
  - Mumbai, Maharashtra, India, 400053
    - Kokilaben Dhirubhai Ambani Hospital & Medical Research Institute-Centre for cancer ( Site 3302)
- National Capital Territory of Delhi
  - New Delhi, National Capital Territory of Delhi, India, 110029
    - All India Institute of Medical Sciences-Department of medical oncology ( Site 3303)
  - New Delhi, National Capital Territory of Delhi, India, 110076
    - Indraprastha Apollo Hospitals-APOLLO RESEARCH INNOVATION ( Site 3301)
  - New Delhi, National Capital Territory of Delhi, India, 110085
    - Rajiv Gandhi Cancer Institute And Research Centre ( Site 3300)
Italy
- - Roma, Italy, 00168
    - Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore ( Site 1801)
- Apulia
  - Bari, Apulia, Italy, 70124
    - Instituto Tumori Giovanni Paolo II-SSD Oncologia Medica per la Patologia Toracica ( Site 1802)
- Lombardy
  - Milan, Lombardy, Italy, 20133
    - Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 1800)
  - Milan, Lombardy, Italy, 20141
    - Istituto Europeo di Oncologia IRCCS-Divisione di Oncologia Toracica ( Site 1803)
- Tuscany
  - Florence, Tuscany, Italy, 50134
    - Azienda Ospedaliera Universitaria Careggi-SOD ONCOLOGIA MEDICA ( Site 1804)
Japan
- - Fukuoka, Japan, 812-8582
    - Kyushu University Hospital ( Site 3400)
  - Hiroshima, Japan, 730-8518
    - Hiroshima City Hiroshima Citizens Hospital ( Site 3419)
  - Niigata, Japan, 951-8566
    - Niigata Cancer Center Hospital ( Site 3403)
  - Okayama, Japan, 700-8558
    - Okayama University Hospital ( Site 3404)
  - Osaka, Japan, 541-8567
    - Osaka Prefectural Hospital Organization Osaka International Cancer Institute ( Site 3410)
  - Osaka, Japan, 545-0051
    - Osaka Metropolitan University Hospital ( Site 3412)
- Aichi-ken
  - Toyoake, Aichi-ken, Japan, 470-1192
    - Fujita Health University Hospital ( Site 3409)
- Ehime
  - Tōon, Ehime, Japan, 791-0295
    - Ehime University Hospital ( Site 3411)
- Fukuoka
  - Fukuoka, Fukuoka, Japan, 811-1395
    - National Hospital Organization Kyushu Cancer Center ( Site 3401)
- Gunma
  - Ōta, Gunma, Japan, 373-8550
    - Gunma Prefectural Cancer Center ( Site 3413)
- Ishikawa-ken
  - Kanazawa, Ishikawa-ken, Japan, 920-8641
    - Kanazawa University Hospital ( Site 3402)
- Kanagawa
  - Kawasaki, Kanagawa, Japan, 216-8511
    - St. Marianna University Hospital ( Site 3415)
  - Yokohama, Kanagawa, Japan, 241-8515
    - Kanagawa Cancer Center ( Site 3416)
- Miyagi
  - Natori-shi, Miyagi, Japan, 981-1293
    - Miyagi Cancer Center ( Site 3406)
- Osaka
  - Hirakata, Osaka, Japan, 573-1191
    - Kansai Medical University Hospital ( Site 3414)
- Saitama
  - Kitaadachi-gun, Saitama, Japan, 362-0806
    - Saitama Prefectural Cancer Center ( Site 3417)
- Shizuoka
  - Sunto-gun, Shizuoka, Japan, 411-8777
    - Shizuoka Cancer Center ( Site 3405)
- Tokyo
  - Chūō, Tokyo, Japan, 104-0045
    - National Cancer Center Hospital ( Site 3408)
  - Ōta-ku, Tokyo, Japan, 143-8541
    - Toho University Omori Medical Center ( Site 3407)
Malaysia
- Kuala Lumpur
  - Lembah Pantai, Kuala Lumpur, Malaysia, 59100
    - University Malaya Medical Centre ( Site 3507)
  - Putrajaya, Kuala Lumpur, Malaysia, 62250
    - National Cancer Institute-Radiotherapy and Oncology ( Site 3504)
- Pahang
  - Kuantan, Pahang, Malaysia, 25100
    - Hospital Tengku Ampuan Afzan ( Site 3506)
- Pulau Pinang
  - George Town, Pulau Pinang, Malaysia, 10450
    - Hospital Pulau Pinang-Oncology, radiotherapy and palliat ( Site 3501)
- Sarawak
  - Kuching, Sarawak, Malaysia, 93586
    - Sarawak General Hospital-Radiotherapy Unit ( Site 3508)
Mexico
- - Oaxaca City, Mexico, 68000
    - Oaxaca Site Management Organization S.C. ( Site 0701)
  - Oaxaca City, Mexico, 68020
    - Centro de Investigacion Clinica de Oaxaca ( Site 0704)
- Jalisco
  - Guadalajara, Jalisco, Mexico, 44630
    - CIO - Centro de Inmuno-Oncología de Occidente ( Site 0700)
- Mexico City
  - Mexico City, Mexico City, Mexico, 06700
    - Arké SMO S.A. de C.V. ( Site 0706)
- Nuevo León
  - Monterrey, Nuevo León, Mexico, 64460
    - Hospital Universitario "Dr. Jose Eleuterio Gonzalez"-Servicio de Oncología ( Site 0705)
Poland
- Kuyavian-Pomeranian Voivodeship
  - Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland, 85-796
    - Centrum Onkologii im. Prof. Franciszka Lukaszczyka-Ambulatorium Chemioterapii ( Site 2003)
- Masovian Voivodeship
  - Warsaw, Masovian Voivodeship, Poland, 02-781
    - Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworow Pluca i Klatki Pier ( Site 2000)
- Podlaskie Voivodeship
  - Bialystok, Podlaskie Voivodeship, Poland, 15-027
    - Bialostockie Centrum Onkologii ( Site 2010)
- Silesian Voivodeship
  - Gliwice, Silesian Voivodeship, Poland, 44-102
    - Narodowy Instytut Onkologii - Oddzial w Gliwicach-II Klinika Radioterapi i Chemioterapii ( Site 2002)
South Korea
- - Seoul, South Korea, 03312
    - The Catholic University of Korea, Eunpyeong St. Mary's Hospital ( Site 3812)
  - Seoul, South Korea, 05505
    - Asan Medical Center ( Site 3810)
  - Seoul, South Korea, 06351
    - Samsung Medical Center ( Site 3811)
  - Seoul, South Korea, 08308
    - Korea University Guro Hospital ( Site 3808)
- Kyonggi-do
  - Goyang-si, Kyonggi-do, South Korea, 10408
    - National Cancer Center ( Site 3803)
  - Seongnam, Kyonggi-do, South Korea, 13620
    - Seoul National University Bundang Hospital ( Site 3807)
  - Suwon, Kyonggi-do, South Korea, 16247
    - The Catholic University Of Korea St. Vincent's Hospital ( Site 3800)
  - Suwon, Kyonggi-do, South Korea, 16499
    - Ajou University Hospital ( Site 3813)
- Kyongsangnam-do
  - Pusan, Kyongsangnam-do, South Korea, 50612
    - Pusan National University Yangsan Hospital ( Site 3802)
- North Chungcheong
  - Cheongju-si, North Chungcheong, South Korea, 28644
    - Chungbuk National University Hospital ( Site 3804)
- Pusan-Kwangyokshi
  - Busan, Pusan-Kwangyokshi, South Korea, 49241
    - Pusan National University Hospital ( Site 3805)
- Taegu-Kwangyokshi
  - Daegu, Taegu-Kwangyokshi, South Korea, 42601
    - Keimyung University Dongsan Hospital CRC room 1 ( Site 3814)
- Taejon-Kwangyokshi
  - Junggu, Taejon-Kwangyokshi, South Korea, 35015
    - Chungnam national university hospital ( Site 3806)
Spain
- - Huelva, Spain, 21005
    - Hospital Universitario Juan Ramon Jimenez-Oncología Medica ( Site 2323)
  - Seville, Spain, 41009
    - Hospital Universitario Virgen Macarena-Unidad de Investigación Oncológica ( Site 2324)
- Barcelona
  - LHospitalet de Llobregat, Barcelona, Spain, 08908
    - Institut Català d'Oncologia - L'Hospitalet-Medical Oncology ( Site 2321)
- La Coruna
  - Santiago de Compostela, La Coruna, Spain, 15706
    - CHUS - Hospital Clinico Universitario-Servicio de Oncologia ( Site 2322)
Sweden
- Stockholm County
  - Stockholm, Stockholm County, Sweden, 171 64
    - Karolinska Universitetssjukhuset Solna ( Site 2401)
Taiwan
- - Changhua, Taiwan, 50006
    - Changhua Christian Hospital ( Site 3904)
  - Hsinchu, Taiwan, 300
    - National Taiwan University Hospital - Hsinchu branch ( Site 3900)
  - Kaohsiung City, Taiwan, 83301
    - Chang Gung Memorial Hospital at Kaohsiung ( Site 3905)
  - New Taipei City, Taiwan, 220
    - Far Eastern Memorial Hospital ( Site 3912)
  - Taichung, Taiwan, 40705
    - Taichung Veterans General Hospital-Chest ( Site 3910)
  - Taipei, Taiwan, 10449
    - Mackay Memorial Hospital-Chest Medicine ( Site 3902)
  - Taipei, Taiwan, 10002
    - National Taiwan University Hospital-Oncology ( Site 3908)
  - Taipei, Taiwan, 110301
    - Taipei Medical University Hospital ( Site 3903)
  - Taoyuan, Taiwan, 333
    - Chang Gung Medical Foundation-Linkou Branch-Clinic of Chest Medicine ( Site 3911)
- Tainan
  - Tainan, Tainan, Taiwan, 704
    - National Cheng Kung University Hospital ( Site 3901)
  - Tainan, Tainan, Taiwan, 73657
    - Chi Mei Hospital - Liouying Branch ( Site 3909)
- Taipei
  - Taipei City, Taipei, Taiwan, 106
    - National Taiwan University Cancer Center (NTUCC) ( Site 3907)
Thailand
- Bangkok
  - Bangkoknoi, Bangkok, Thailand, 10700
    - Faculty of Medicine Siriraj Hospital ( Site 4004)
  - Dusit, Bangkok, Thailand, 10300
    - Bangkok Metropolitan Administration Medical College and Vajira Hospital ( Site 4006)
- Changwat Khon Kaen
  - Muang, Changwat Khon Kaen, Thailand, 40002
    - Faculty of Medicine - Khon Kaen University ( Site 4002)
- Changwat Lampang
  - Lampang, Changwat Lampang, Thailand, 52000
    - Lampang Cancer Hospital ( Site 4000)
- Changwat Ratchaburi
  - Ratchathewi, Changwat Ratchaburi, Thailand, 10400
    - Ramathibodi Hospital ( Site 4001)
- Changwat Songkhla
  - Hat Yai, Changwat Songkhla, Thailand, 90110
    - Songklanagarind hospital ( Site 4003)
- Chiang Mai
  - Muang, Chiang Mai, Thailand, 50200
    - Maharaj Nakorn Chiang Mai Hospital ( Site 4005)
Turkey (Türkiye)
- - Adana, Turkey (Türkiye), 01140
    - Adana Medical Park Seyhan Hastanesi-Medikal Onkoloji ( Site 2504)
  - Ankara, Turkey (Türkiye), 06230
    - Hacettepe Universite Hastaneleri-oncology hospital ( Site 2501)
  - Ankara, Turkey (Türkiye), 06520
    - Memorial Ankara Hastanesi-Medical Oncology ( Site 2505)
  - Ankara, Turkey (Türkiye), 06800
    - Ankara Bilkent Şehir Hastanesi ( Site 2500)
  - Izmir, Turkey (Türkiye), 35575
    - I.E.U. Medical Point Hastanesi-Oncology ( Site 2503)
United States
- California
  - Oakland, California, United States, 94611
    - Kaiser Permanente - Oakland ( Site 0054)
  - Roseville, California, United States, 95661
    - Kaiser Permanente - Roseville ( Site 0055)
  - San Francisco, California, United States, 94115
    - Kaiser Permanente - San Francisco ( Site 0056)
  - Santa Clara, California, United States, 95051
    - Kaiser Permanente - Santa Clara ( Site 0057)
  - Vallejo, California, United States, 94589
    - Kaiser Permanente-Kaiser Permanente ( Site 0036)
  - Walnut Creek, California, United States, 94596
    - Kaiser Permanente - Walnut Creek ( Site 0058)
- Florida
  - Orange City, Florida, United States, 32763
    - Mid Florida Hematology and Oncology Center ( Site 0005)
- Georgia
  - Marietta, Georgia, United States, 30060
    - Northwest Georgia Oncology Centers, a Service of Wellstar Cobb Hospital-Research ( Site 0003)
- Michigan
  - Ann Arbor, Michigan, United States, 48109
    - University of Michigan ( Site 0009)
- Missouri
  - Springfield, Missouri, United States, 65807
    - Cox Medical Center North - Cox Medical Center/ Hematology/Medical Oncology ( Site 0051)
- New Jersey
  - East Brunswick, New Jersey, United States, 08816
    - Astera Cancer Care ( Site 0032)
- New York
  - Stony Brook, New York, United States, 11794
    - Stony Brook University-Cancer Center ( Site 0038)
- North Dakota
  - Fargo, North Dakota, United States, 58122
    - Sanford Fargo Medical Center ( Site 0028)
- South Dakota
  - Sioux Falls, South Dakota, United States, 57104
    - Sanford Cancer Center ( Site 0024)
- Texas
  - Fort Worth, Texas, United States, 76104
    - John Peter Smith Hospital ( Site 0065)
  - Houston, Texas, United States, 77030
    - University of Texas MD Anderson ( Site 0063)
  - Houston, Texas, United States, 77090
    - Millennium Research & Clinical Development ( Site 0035)
Vietnam
- - Ho Chi Minh City, Vietnam, 700000
    - Cho Ray Hospital ( Site 4190)
  - Ho Chi Minh City, Vietnam, 700000
    - Tam Anh TP.HCM General Hospital ( Site 4196)
- Hanoi
  - Hanoi, Hanoi, Vietnam, 100000
    - Hanoi Oncology Hospital ( Site 4198)
  - Hanoi, Hanoi, Vietnam, 100000
    - K Hospital - National Cancer Hospital ( Site 4193)
  - Hanoi, Hanoi, Vietnam, 100000
    - National Lung Hospital-Oncology Department ( Site 4194)
- Ho Chi Minh
  - Ho Chi Minh City, Ho Chi Minh, Vietnam, 700000
    - Oncology Hospital ( Site 4191)
  - Tan Binh District, Ho Chi Minh, Vietnam, 700000
    - Thong Nhat Hospital ( Site 4192)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

Adult
Older Adult

Accepts Healthy Volunteers

Description

Inclusion Criteria:

Histologically or cytologically confirmed diagnosis of advanced-stage nonsquamous non-small cell lung cancer (NSCLC).
Participants who have adverse events (AEs) due to previous anticancer therapies must have recovered to Grade ≤1 or baseline.
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.
Participants with history of Hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable.
Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy.
Life expectancy of at least 3 months.

Exclusion Criteria:

Predominantly squamous cell histology NSCLC.
History of second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 3 years.
Grade ≥2 peripheral neuropathy.
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.
Uncontrolled, or significant cardiovascular disease or cerebrovascular disease.
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. Administration of killed vaccines are allowed.
Received radiation therapy to the lung that is >30 Gray within 6 months of the first dose of study intervention.
Known active central nervous system metastases and/or carcinomatous meningitis.
Active infection requiring systemic therapy.
History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
Concurrent active HBV and HCV infection.
History of allogeneic tissue/solid organ transplant.
Participants who have not adequately recovered from major surgery or have ongoing surgical complications.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Interventional Model: Parallel Assignment
Masking: Single

Number of Arms

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Pemetrexed Plus Carboplatin Participants receive, via IV infusion, 500 mg/m2 pemetrexed every 3 weeks (Days 1 and 22 of every 6-week cycle) plus area under the curve (AUC) 5 mg/mL*min carboplatin every 3 weeks (Days 1 and 22 of every 6-week cycle for 4 doses), then 500 mg/m2 pemetrexed every 3 weeks until discontinuation criteria is met.	Drug: Pemetrexed 500 mg/m^2 via IV infusion Drug: Carboplatin AUC 5 mg/mL*min via IV infusion
Experimental: Sacituzumab tirumotecan Participants receive 4 mg/kg sacituzumab tirumotecan via intravenous (IV) infusion every 2 weeks (Days 1, 15, and 29 of every 6-week cycle) until discontinuation criteria is met.	Drug: H2 Receptor Antagonist Administered as rescue medication per approved product label Drug: Acetaminophen (or equivalent) Administered as rescue medication per approved product label Drug: Dexamethasone (or equivalent) Administered as rescue medication per approved product label Biological: Sacituzumab tirumotecan 4 mg/kg via IV infusion Other Names: SKB264 MK-2870 Drug: Steroid Mouthwash (dexamethasone or equivalent) Administered as rescue medication per approved product label Drug: H1 Receptor Antagonist Administered as rescue medication per approved product label

Participant Group / Arm

Intervention / Treatment

Active Comparator: Pemetrexed Plus Carboplatin

Participants receive, via IV infusion, 500 mg/m2 pemetrexed every 3 weeks (Days 1 and 22 of every 6-week cycle) plus area under the curve (AUC) 5 mg/mL*min carboplatin every 3 weeks (Days 1 and 22 of every 6-week cycle for 4 doses), then 500 mg/m2 pemetrexed every 3 weeks until discontinuation criteria is met.

Drug: Pemetrexed

500 mg/m^2 via IV infusion

Drug: Carboplatin

AUC 5 mg/mL*min via IV infusion

Experimental: Sacituzumab tirumotecan

Participants receive 4 mg/kg sacituzumab tirumotecan via intravenous (IV) infusion every 2 weeks (Days 1, 15, and 29 of every 6-week cycle) until discontinuation criteria is met.

Drug: H2 Receptor Antagonist