A Study to Assess Efficacy and Safety of Pembrolizumab With or Without Sacituzumab Tirumotecan (MK- 2870) in Adult Participants With Resectable Non Small Cell Lung Cancer (NSCLC) Not Achieving Pathological Complete Response (pCR) (MK-2870-019)

Phase 3

Recruiting

• Conditions: Non Small Cell Lung Cancer
• Interventions: Biological: Sacituzumab tirumotecan; Biological: Pembrolizumab; Drug: Cisplatin; Drug: Rescue medication; Drug: Pemetrexed; Drug: Gemcitabine; Drug: Carboplatin; Drug: Paclitaxel

• Registration Number: NCT06312137
• Lead Sponsor: Merck Sharp & Dohme LLC

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-03-08
• Study First Submitted QC: 2024-03-08
• Study First Posted: 2024-03-15
• Study Start: 2024-04-03
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-11
• Last Update Posted: 2025-07-14
• Primary Completion: 2034-02-21
• Study Completion: 2034-10-23

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 780

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 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) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease

• 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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pembrolizumab + Sacituzumab tirumotecan	Pembrolizumab	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).
Pembrolizumab + Sacituzumab tirumotecan	Rescue medication	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).
Pembrolizumab	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).
Pembrolizumab	Pemetrexed	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).
Pembrolizumab	Gemcitabine	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).
Pembrolizumab	Cisplatin	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).
Pembrolizumab	Carboplatin	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).
Pembrolizumab	Paclitaxel	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).
Pembrolizumab + Sacituzumab tirumotecan	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).

Primary Outcome Measures

Name	Time	Method
Disease-free survival (DFS) as assessed by Blinded Independent Central Review (BICR)	Up to ~ 93 months	DFS is defined as the time from randomization to any recurrence (local, locoregional, regional or distant), occurrence of new primary NSCLC, or death due to any cause, whichever occurs first.

Secondary Outcome Measures

Name	Time	Method
Distant metastasis-free survival (DMFS) as assessed by investigator	Up to ~ 118 months	DMFS is defined as the time from randomization to the first documented distant metastasis or death due to any cause, whichever occurs first. Distant metastasis refers to cancer that has spread from the original (primary) tumor to distant organs or distant lymph nodes.
Disease-Free Survival (DFS) as assessed by investigator	Up to ~ 118 months	DFS is defined as the time from randomization to any recurrence (local, locoregional, regional or distant), occurrence of new primary NSCLC, or death due to any cause, whichever occurs first.
Overall Survival (OS)	Up to ~ 118 months	OS is defined as the time from randomization to death due to any cause.
Lung Cancer Specific Survival (LCSS)	Up to ~ 118 months	LCSS is defined as the time from randomization to the date of death due to lung cancer.
Number of Participants Who Experience an Adverse Event (AE)	Up to ~ 118 months	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
Number of Participants Who Discontinue Study Intervention Due to AEs	Up to ~ 118 months	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who discontinue study treatment due to an AE will be presented.
Change from Baseline in Global Health Status/Quality of Life (QoL) score (Quality of Life Questionnaire (QLQ)-C30 Items 29 and 30)	Baseline and up to ~118 months	The European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ) is a psychometrically and clinically validated instrument appropriate for assessing the health-related quality of life (HRQoL) of cancer patients in oncology studies. Each scale or item is scored between 0 and 100, for the global health status or QoL a higher value indicates a better level of function.
Change from Baseline in Physical Functioning Score (QLQ-C30 Items 1 to 5)	Baseline and up to ~118 months	The EORTC-QLQ is a psychometrically and clinically validated instrument appropriate for assessing the HRQoL of cancer patients in oncology studies. Each scale or item is scored between 0 and 100, for all physical functional scales, a higher value indicates a better level of function.
Change from Baseline in Role Functioning Score (QLQ-C30 Items 6 and 7)	Baseline and up to ~118 months	The EORTC-QLQ is a psychometrically and clinically validated instrument appropriate for assessing the HRQoL of cancer patients in oncology studies. Each scale or item is scored between 0 and 100, for all role functional scales, a higher value indicates a better level of function.
Change from Baseline in Dyspnea scores (QLQ-C30 Item 8)	Baseline and up to ~118 months	The EORTC-QLQ is a psychometrically and clinically validated instrument appropriate for assessing the HRQoL of cancer patients in oncology studies. Each scale or item is scored between 0 and 100, for symptom scales such as dyspnea, a higher value indicates increased severity of symptoms.
Change from Baseline in Coughing scores (QLQ-LC24 Items 31 and 52)	Baseline and up to ~118 months	The lung cancer module of the EORTC, QLQ-LC24 is a revised and updated version of the Lung Cancer Module QLQ-LC13 and is a supplementary lung cancer specific module to be used along with EORTC QLQ C30. The QLQ-LC24 incorporates 4 multi-item scales to assess coughing, shortness of breath, hair problems, and fear of progression, for symptom scales as for cough, a higher value indicates increased severity of symptoms.
Change from Baseline in Chest pain scores (QLQ-LC24 Item 40)	Baseline and up to ~118 months	The lung cancer module of the EORTC, QLQ-LC24 is a revised and updated version of the Lung Cancer Module QLQ-LC13 and is a supplementary lung cancer specific module to be used along with EORTC QLQ C30. The QLQ-LC24 incorporates 4 multi-item scales to assess coughing, shortness of breath, hair problems, and fear of progression, for symptom scales as for chest pain, a higher value indicates increased severity of symptoms.

Trial Locations

Locations (215)

UAMS Winthrop P. Rockefeller Cancer Institute ( Site 0060); 🇺🇸 Little Rock, Arkansas, United States

Highlands Oncology Group-Research Department ( Site 0062); 🇺🇸 Springdale, Arkansas, United States

Beverly Hills Cancer Center ( Site 0070); 🇺🇸 Beverly Hills, California, United States

The Angeles Clinic and Research Institute ( Site 0040); 🇺🇸 Los Angeles, California, United States

The Angeles Clinic and Research Institute- A Cedars-Sinai Affiliate ( Site 0079); 🇺🇸 Los Angeles, California, United States

San Francisco Oncology Associates ( Site 0066); 🇺🇸 San Francisco, California, United States

Stamford Hospital ( Site 0083); 🇺🇸 Stamford, Connecticut, United States

Mount Sinai Cancer Center ( Site 0038); 🇺🇸 Miami Beach, Florida, United States

Mid Florida Hematology and Oncology Center ( Site 0018); 🇺🇸 Orange City, Florida, United States

Emory University School of Medicine-Phase I ( Site 0056); 🇺🇸 Atlanta, Georgia, United States

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