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)

Non Small Cell Lung Cancer Clinical Trial

Official title:

A Phase 3 Randomized Open-Label Study of Adjuvant Pembrolizumab With or Without MK-2870 in Participants With Resectable Stage II to IIIB (N2) NSCLC Not Achieving pCR After Receiving Neoadjuvant Pembrolizumab With Platinum-based Doublet Chemotherapy Followed by Surgery

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06312137
• Other study ID #: 2870-019
• Secondary ID: 2023-508012-35MK
• Status: Recruiting
• Phase: Phase 3
• Start date: April 3, 2024
• Est. completion date: October 23, 2034

Study information

• Verified date: April 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

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 780
• Est. completion date: October 23, 2034
• Est. primary completion date: February 21, 2034
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

The key inclusion and exclusion criteria include but are not limited to the following:

Inclusion Criteria:

• Has histological 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 epidermal growth factor receptor (EGFR)-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
• Documentation by local test report indicating presence of anaplastic lymphoma kinase (ALK) gene rearrangements
• 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 severe hypersensitivity (Grade =3) to sacituzumab tirumotecan, any of its excipients and/or to another biologic therapy.
• Has a history of allogeneic tissue/solid organ transplant.
• Has not adequately recovered from major surgery or have ongoing surgical complications.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non Small Cell Lung Cancer

Intervention

Biological:
• Sacituzumab tirumotecan
Sacituzumab tirumotecan to be administered as 4mg/kg IV infusion q2w for up to 40 weeks
• Pembrolizumab
Pembrolizumab to be administered 400mg by IV infusion q6w for up to 42 weeks

Drug:
• Cisplatin
Cisplatin is administered as 75 mg/m2 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/m2 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/m2 or 1250 mg/m2 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/m2 or 200 mg/m2 IV infusion q3w for up to 12 weeks as background treatment.

Locations

Country	Name	City	State
Israel	Rambam Health Care Campus-Oncology Division ( Site 2203)	Haifa
Israel	Shaare Zedek Medical Center ( Site 2206)	Jerusalem
Israel	Rabin Medical Center ( Site 2204)	Petah Tikva
Taiwan	National Cheng Kung University Hospital-Clinical Trial Center ( Site 1102)	Tainan
United States	Mid Florida Hematology and Oncology Center ( Site 0018)	Orange City	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Israel,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-free survival (DFS) as assessed by Blinded Independent Central Review (BICR)	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.	Up to ~ 93 months
Secondary	Overall Survival (OS)	OS is defined as the time from randomization to death due to any cause.	Up to ~ 118 months
Secondary	Distant metastasis-free survival (DMFS) as assessed by investigator	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.	Up to ~ 118 months
Secondary	Disease-Free Survival (DFS) as assessed by investigator	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.	Up to ~ 118 months
Secondary	Lung Cancer Specific Survival (LCSS)	LCSS is defined as the time from randomization to the date of death due to lung cancer.	Up to ~ 118 months
Secondary	Number of Participants Who Experience at least One Adverse Event (AE)	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.	Up to ~ 118 months
Secondary	Number of Participants Who Discontinue Study Intervention Due to AEs	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.	Up to ~ 118 months
Secondary	Change from Baseline in Global Health Status/Quality of Life (QoL) score (Quality of Life Questionnaire (QLQ)-C30 Items 29 and 30)	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.	Baseline and up to ~118 months
Secondary	Change from Baseline in Physical Functioning Score (QLQ-C30 Items 1 to 5)	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.	Baseline and up to ~118 months
Secondary	Change from Baseline in Role Functioning Score (QLQ-C30 Items 6 and 7)	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.	Baseline and up to ~118 months
Secondary	Change from Baseline in Dyspnea scores (QLQ-C30 Item 8)	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.	Baseline and up to ~118 months
Secondary	Change from Baseline in Coughing scores (QLQ-LC24 Items 31 and 52)	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.	Baseline and up to ~118 months
Secondary	Change from Baseline in Chest pain scores (QLQ-LC24 Item 40)	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.	Baseline and up to ~118 months

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary