Non Small Cell Lung Cancer
Conditions
Keywords
Carcinoma, Lung cancer, Non-small cell lung cancer
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).
Interventions
BIOLOGICALSacituzumab tirumotecan
Sacituzumab tirumotecan to be administered as 4mg/kg IV infusion q2w for up to 24 weeks
BIOLOGICALPembrolizumab
Pembrolizumab to be administered 400mg by IV infusion q6w for up to 42 weeks
DRUGCisplatin
Cisplatin is administered as 75 mg/m\^2 IV infusion q3w for up to 12 weeks as background treatment in neoadjuvant phase
DRUGPemetrexed
Pemetrexed will be administered in the neoadjuvant phase as 500 mg/m\^2 IV infusion q3w for up to 12 weeks as background treatment in participants with nonsquamous NSCLC.
DRUGGemcitabine
Gemcitabine will be administered in the neoadjuvant phase as 1000 mg/m\^2 or 1250 mg/m\^2 IV infusion on day 1 and day 8 q3w for up to 24 weeks as background treatment in participants with squamous NSCLC.
DRUGCarboplatin
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.
DRUGPaclitaxel
Paclitaxel will be administered in the neoadjuvant phase as 175 mg/m\^2 or 200 mg/m\^2 IV infusion q3w for up to 12 weeks as background treatment.
DRUGRescue medication
Participants are permitted to take rescue medications to prevent hypersensitivity and/or infusion reactions as a premedication to study treatment. Rescue medications include antihistamine, H2 receptor antagonist, acetaminophen or equivalent, dexamethasone or equivalent, and granulocyte colony-stimulating factor. A steroid mouthwash (dexamethasone or equivalent) may be given as prophylaxis for stomatitis/oral mucositis.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Intervention model description
This is a multi site study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
The key inclusion and
Exclusion criteria
include but are not limited to the following: 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Up to ~ 118 months | OS is defined as the time from randomization to death due to any cause. |
| 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. |
| 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. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Czechia, France, Germany, Greece, Hong Kong, Israel, Italy, Japan, Mexico, Netherlands, New Zealand, Norway, Peru, Poland, Portugal, Romania, South Korea, Spain, Switzerland, Taiwan, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTToll Free Number
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed