Sacituzumab Tirumotecan (MK-2870) in Combination With Pembrolizumab Versus Pembrolizumab Alone in Metastatic Non-small Cell Lung Cancer (NSCLC) With Programmed Cell Death Ligand 1 (PD-L1) Tumor Proportion Score (TPS) ≥ 50% (MK-2870-007)

Non-small Cell Lung Cancer (NSCLC) Clinical Trial

Official title:

A Randomized, Open-label, Phase 3 Study of MK-2870 in Combination With Pembrolizumab Compared to Pembrolizumab Monotherapy in the First-line Treatment of Participants With Metastatic Non-small Cell Lung Cancer With PD-L1 TPS Greater Than or Equal to 50%

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06170788
• Other study ID #: 2870-007
• Secondary ID: MK-2870-0072023-
• Status: Recruiting
• Phase: Phase 3
• Start date: December 15, 2023
• Est. completion date: May 27, 2030

Study information

• Verified date: June 2024
• Source: Merck Sharp & Dohme LLC
• Contact: Toll Free Number
• Phone: 1-888-577-8839
• Email: Trialsites[@]merck.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of the study is to compare sacituzumab tirumotecan combined with pembrolizumab to pembrolizumab alone with respect to overall survival (OS). The primary hypothesis is that the combination of sacituzumab tirumotecan and pembrolizumab is superior to pembrolizumab alone with respect to OS.

All participants who have completed the first course of pembrolizumab may be eligible for up to an additional 9 cycles of pembrolizumab monotherapy if there is blinded independent central review (BICR)-verified progressive disease by Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) after initial treatment.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 614
• Est. completion date: May 27, 2030
• Est. primary completion date: January 25, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of squamous or nonsquamous NSCLC

• Confirmation that epidermal growth factor receptor- (EGFR-), anaplastic lymphoma kinase- (ALK-), or proto-oncogene tyrosine-protein kinase ROS (ROS1-) directed therapy is not indicated as primary therapy

• Provided tumor tissue that demonstrates programmed cell death ligand 1 (PD-L1) expression in =50% of tumor cells as assessed by an immunohistochemistry (IHC) central laboratory

• An Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 7 days before randomization.

• A life expectancy of at least 3 months.

• Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART)

Exclusion Criteria:

• Diagnosis of small cell lung cancer or, for mixed tumors, presence of small cell elements.

• Has Grade =2 peripheral neuropathy.

• History of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or corneal disease that prevents/delays corneal healing.

• Has active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, or chronic diarrhea).

• Has uncontrolled, significant cardiovascular disease or cerebrovascular disease within the 6 months preceding study intervention.

• Received prior systemic anticancer therapy for their metastatic NSCLC.

• Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor Note: Prior treatment with an anti-PD-1, anti-PD- L1, or anti-PD-L2 agent in the neoadjuvant or adjuvant setting for nonmetastatic resectable NSCLC is allowed as long as therapy was completed at least 12 months before diagnosis of metastatic NSCLC.

• Received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization.

• Received radiation therapy to the lung that is >30 Gy 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. Administration of killed vaccines are allowed.

• Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy

• Known additional malignancy that is progressing or has required active treatment within the past 3 years.

• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.

• Known intolerance to sacituzumab tirumotecan or pembrolizumab and/or any of their excipients; for pembrolizumab, severe hypersensitivity (=Grade 3) is exclusionary.

• Known hypersensitivity to sacituzumab tirumotecan or other biologic therapy.

• Active autoimmune disease that has required systemic treatment in the past 2 years.

• History of (noninfectious) pneumonitis/interstitial lung disease (ILD) that required steroids or has current pneumonitis/ILD.

• Active infection requiring systemic therapy

• Concurrent active Hepatitis B and Hepatitis C virus infection.

• Human immunodeficiency virus (HIV)-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.

• History of allogeneic tissue/solid organ transplant.

• Requires treatment with a strong inhibitor or inducer of Cytochrome P450 3A4 (CYP3A4) at least 14 days before the first dose of study intervention and throughout the study.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer (NSCLC)

Intervention

Biological:
• Sacituzumab tirumotecan
IV infusion
• Pembrolizumab
IV infusion

Locations

Country	Name	City	State
Argentina	Hospital Aleman-Oncology ( Site 0300)	Buenos Aires	Caba
Argentina	Hospital Británico de Buenos Aires-Oncology ( Site 0304)	Ciudad autónoma de Buenos Aires	Caba
Argentina	Instituto Alexander Fleming ( Site 0306)	Ciudad Autónoma de Buenos Aires	Buenos Aires
Argentina	Centro Privado de RMI Río Cuarto S.A. II ( Site 0310)	Río Cuarto	Cordoba
Argentina	Instituto de Oncología de Rosario ( Site 0301)	Rosario	Santa Fe
Australia	Grampians Health-Medical Oncology ( Site 3001)	Ballarat Central	Victoria
Australia	Northern Hospital ( Site 3003)	Epping	Victoria
Australia	Port Macquarie - Mid North Coast Cancer Institute-Medical Oncology ( Site 3002)	Port Macquarie	New South Wales
Australia	Westmead Hospital-Department of Medical Oncology ( Site 3000)	Westmead	New South Wales
Chile	Bradfordhill-Clinical Area ( Site 0507)	Santiago	Region M. De Santiago
Chile	FALP-UIDO ( Site 0509)	Santiago	Region M. De Santiago
Chile	Orlandi Oncologia-Oncology ( Site 0504)	Santiago	Region M. De Santiago
Chile	Clinica Universidad Catolica del Maule-Oncology ( Site 0501)	Talca	Maule
China	Beijing Peking Union Medical College Hospital-pneumology department ( Site 3100)	Beijing	Beijing
China	Southern Medical University Nanfang Hospital-Depatrment of Respiratory and Critical Care Medicine (	Guangzhou	Guangdong
China	The Second People's Hospital of Neijiang ( Site 3140)	Neijiang	Sichuan
China	Taizhou Hospital of Zhejiang Province-Respiratory ( Site 3114)	Taizhou	Zhejiang
China	Affiliated Hospital of Jiangnan University(Wuxi Fourth People's Hospital ) ( Site 3113)	Wuxi	Jiangsu
Denmark	Aalborg Universitetshospital, Syd-Department of Oncology ( Site 1201)	Aalborg	Nordjylland
Denmark	Regionshospitalet Gødstrup-Kræftklinikken ( Site 1204)	Herning	Midtjylland
Denmark	Odense Universitetshospital ( Site 1200)	Odense	Syddanmark
France	Clinique de l'Europe-Service de pneumologie ( Site 1304)	Amiens	Somme
France	Centre Hospitalier de la Côte Basque ( Site 1300)	Bayonne	Pyrenees-Atlantiques
France	L HOPITAL NORD OUEST ( Site 1310)	Gleize	Rhone
France	Centre Hospitalier Universitaire de Limoges - Hôpital Dupuyt-Unité d'oncologie thoracique et cutané	Limoges	Limousin
France	Hôpital Saint Joseph-ONCOLOGY ( Site 1308)	Marseille	Bouches-du-Rhone
France	Institut Régional du Cancer Montpellier-Medical Oncology ( Site 1309)	Montpellier	Herault
France	Centre d'Oncologie de Gentilly ( Site 1301)	Nancy	Meurthe-et-Moselle
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS -Medical Oncology ( Site 1806)	Roma
Korea, Republic of	Chungbuk National University Hospital-Internal medicine ( Site 3804)	Cheongju-si	Chungbuk
Korea, Republic of	Keimyung University Dongsan Hospital CRC room 1 ( Site 3807)	Daegu	Taegu-Kwangyokshi
Korea, Republic of	National Cancer Center ( Site 3801)	Goyang-si	Kyonggi-do
Korea, Republic of	Samsung Medical Center-Division of Hematology/Oncology ( Site 3802)	Seoul
Korea, Republic of	Ajou University Hospital-Hematology-Oncology ( Site 3806)	Suwon-si	Kyonggi-do
Korea, Republic of	The Catholic University Of Korea St. Vincent's Hospital-Medical Oncology ( Site 3800)	Suwon-si	Kyonggi-do
Netherlands	ETZ Elisabeth-Department of Pulmonary Diseases ( Site 1902)	Tilburg	Noord-Brabant
Spain	Hospital Universitari Vall d'Hebron-Oncology ( Site 2330)	Barcelona
Spain	Hospital Jerez de la Frontera-UGC Oncología ( Site 2333)	Jerez de la Frontera	Cadiz
Spain	HOSPITAL UNIVERSITARIO QUIRONSALUD MADRID-ONCOLOGIA MEDICA ( Site 2331)	Pozuelo de Alarcon	Madrid
Taiwan	National Taiwan University Hospital - Hsinchu branch ( Site 3901)	Hsinchu
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital ( Site 3904)	Kaohsiung
Taiwan	Chang Gung Memorial Hospital at Kaohsiung ( Site 3902)	Kaohsiung Niao Sung Dist	Kaohsiung
Taiwan	Taichung Veterans General Hospital-Chest ( Site 3905)	Taichung
Taiwan	National Cheng Kung University Hospital-Clinical Trial Center ( Site 3903)	Tainan
Taiwan	Chi Mei Hospital - Liouying Branch ( Site 3908)	Tainan City	Tainan
Taiwan	National Taiwan University Hospital-Oncology ( Site 3906)	Taipei
Taiwan	National Taiwan University Cancer Center (NTUCC) ( Site 3907)	Taipei City	Taipei
Thailand	Maharaj Nakorn Chiang Mai Hospital-Chiang Mai Clinical Trial Unit (CM-CTU) ( Site 4001)	Chiang Mai
Turkey	Adana Medical Park Seyhan Hastanesi-Medikal Onkoloji ( Site 2507)	Adana
Turkey	Ankara Bilkent Sehir Hastanesi ( Site 2500)	Ankara
Turkey	Hacettepe Universite Hastaneleri-oncology hospital ( Site 2501)	Ankara
Turkey	Memorial Ankara Hastanesi-Medical Oncology ( Site 2505)	Ankara
Turkey	Pamukkale University Medical Faculty, Fahri Goksin Oncology Centre-Oncolgyy-Hematology ( Site 2510)	Denizli
Turkey	Ondokuz Mayis Universitesi ( Site 2509)	Samsun
Turkey	Medipol Mega Universite Hastanesi-oncology ( Site 2508)	Stanbul	Istanbul
Turkey	Erciyes University ( Site 2511)	Talas	Kayseri
United States	Roy and Patricia Disney Family Cancer Center - Providence Saint Joseph Medical Center ( Site 0130)	Burbank	California
United States	Good Samaritan Regional Medical Center-Samaritan Pastega Regional Cancer Center ( Site 0117)	Corvallis	Oregon
United States	Hattiesburg Clinic Hematology/Oncology ( Site 0104)	Hattiesburg	Mississippi
United States	Oncology Consultants P.A. ( Site 0129)	Houston	Texas
United States	The University of Louisville, James Graham Brown Cancer Center ( Site 0121)	Louisville	Kentucky
United States	Northwest Georgia Oncology Centers, a Service of Wellstar Cobb Hospital-Research ( Site 0106)	Marietta	Georgia
United States	Allina Health Cancer Institute - Abbott Northwestern Hospital ( Site 0115)	Minneapolis	Minnesota
United States	Renown Regional Medical Center-Renown Health Medical Oncology ( Site 0134)	Reno	Nevada

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Chile,  China,  Denmark,  France,  Italy,  Korea, Republic of,  Netherlands,  Spain,  Taiwan,  Thailand,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)	OS is defined as the time from randomization to death from any cause.	Up to approximately 48 months
Secondary	Progression free survival (PFS)	PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on BICR or death due to any cause, whichever occurs first	Up to approximately 48 months
Secondary	Objective Response (OR)	The OR is defined as a confirmed complete response (CR) or partial response (PR) per RECIST 1.1 as assessed by BICR.	Up to approximately 48 months
Secondary	Duration of Response (DOR)	For participants who demonstrate confirmed CR or PR per RECIST 1.1 as assessed by BICR, duration of response is defined as the time from the first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first.	Up to approximately 48 months
Secondary	Change from Baseline in Global Health Status/Quality of Life (QOL) [European Organisation for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30) 29 Items and 30] Score	Change from baseline in the score of EORTC QLQ-C30 Items 29 and 30 will be presented. The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to Items 29 and 30 ("How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1=Very Poor to 7=Excellent). A higher score indicates a better overall outcome.	Baseline and up to approximately 24 months
Secondary	Change From Baseline in Dyspnea (EORTC QLQ-C30 Item 8) Score	Change from baseline in the score of EORTC QLQ-C30 Item 8 will be presented. The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant response to the question "Were you short of breath?" is scored on a 4-point scale (1=Not at All to 4=Very Much). A higher score indicates a worse level of dyspnea.	Baseline and up to approximately 24 months
Secondary	Change From Baseline in Cough (EORTC QLQ-LC13 Item 31) Score	Change from baseline in the score of EORTC QLQ-C13 Item 31 will be presented. The EORTC QLQ-C13 is a lung cancer specific health-related quality-of life (QoL) questionnaire. Participant response to the question "Have you coughed?" is scored on a 4-point scale (1=Not at All to 4=Very Much). A higher score indicates more frequent coughing.	Baseline and up to approximately 24 months
Secondary	Change From Baseline in Chest Pain (EORTC QLQ-LC13 item 40) Score	The EORTC QLQ-LC13 is a lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQ-C30. Participant responses to the question "Have you had pain in your chest?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in chest pain (EORTC QLQ-LC13 Item 40) score will be presented. A lower score indicates a better outcome.	Baseline and up to approximately 24 months
Secondary	Time to Deterioration (TTD) Based on Change From Baseline in Global Health Status (GHS)/ QOL Score (EORTC QLQ-C30 Item 29 and 30)	The TTD in GHS/QOL score (EORTC QLQ-C30 Items 29 and 30) will be presented. Participant responses to Items 29 and 30 ("How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1=Very Poor to 7=Excellent). A higher score indicates a better overall outcome. TTD as assessed based on a negative change (decrease in score) from Baseline in GHS/QOL score. A longer TTD indicates a better outcome.	Up to approximately 24 months
Secondary	Time to Deterioration (TTD) Based on Change From Baseline in Dyspnea Score (EORTC QLQ-C30 Item 8)	The TTD in Dyspnea score (EORTC QLQ-C30 Item 8) will be presented. Participant response to the question "Were you short of breath?" is scored on a 4-point scale (1=Not at All to 4=Very Much). A higher score indicates a worse level of dyspnea. TTD is assessed based on the time to a negative change (increase in score) from baseline. A longer TTD indicates a better outcome.	Up to approximately 24 months
Secondary	Time to Deterioration (TTD) Based on Change From Baseline in Cough Score (EORTC QLQ-LC13 Item 31).	The TTD in Cough score (EORTC QLQ-LC13 Item 31) will be presented. Participant response to the question "Have you coughed?" is scored on a 4-point scale (1=Not at All to 4=Very Much). A higher score indicates more frequent coughing. TTD is assessed based on the time to a negative change (increase in score) from baseline. A longer TTD indicates a better outcome.	Up to approximately 24 months
Secondary	Time to Deterioration (TTD) Based on Change From Baseline in Chest Pain Score (EORTC QLQ-LC13 Item 40)	The TTD in Chest Pain score (EORTC QLQ-LC13 Item 40) will be presented. Participant response to the question "Have you had pain in your chest?" is scored on a 4-point scale (1=Not at All to 4=Very Much). A higher score indicates a worse level of chest pain. TTD is assessed based on the time to a negative change (increase in score) from baseline. A longer TTD indicates a better outcome.	Up to approximately 24 months
Secondary	Percentage of Participants That Experience at Least 1 Adverse Event	An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The percentage of participants who experience an AE will be presented.	Up to approximately 27 months
Secondary	Percentage of Participants Who Discontinue Study Treatment Due to an AE	The percentage of participants who discontinue study treatment due to an AE will be presented.	Up to approximately 24 months

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary