Non-small Cell Lung Cancer (NSCLC)
Conditions
Keywords
Anaplastic lymphoma kinase (ALK), Antibody-drug conjugate (ADC), Epidermal growth factor receptor (EGFR), Trophoblast cell-surface antigen 2 (TROP2)
Brief summary
The purpose of this study is to evaluate sacituzumab tirumotecan versus chemotherapy (docetaxel or pemetrexed) for the treatment of previously-treated non-small cell lung cancer (NSCLC) with exon 19del or exon 21 L858R EGFR mutations (hereafter referred to as EGFR mutations or EGFR-mutated) or any of the follow genomic alterations: ALK gene rearrangements, ROS1 rearrangements, BRAF V600E mutations, NTRK gene fusions, MET exon 14 skipping mutations, RET rearrangements, or less common EGFR point mutations of exon 20 S768I, exon 21 L861Q, or exon 18 G719X mutations. The primary hypothesis is that sacituzumab tirumotecan is superior to chemotherapy with respect to overall survival (OS) in NSCLC with EGFR mutations.
Interventions
BIOLOGICALSacituzumab tirumotecan
4 mg/kg of MK-sacituzumab tirumotecan by IV infusion
DRUGDocetaxel
75 mg/m\^2 of docetaxel by IV Infusion
DRUGPemetrexed
500 mg/m\^2 of pemetrexed by IV infusion
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
The main inclusion and
Exclusion criteria
include but are not limited to the following: Inclusion Criteria: * Histologically- or cytologically-documented advanced (Stage III not eligible for resection or curative radiation) or metastatic non-squamous NSCLC with specific mutations. * Documentation of locally assessed radiological disease progression while on or after last treatment based on Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1. * Participants with genome mutations must have received 1 or 2 prior lines of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI), including a third generation TKI for participants with a T790M mutation; and 1 platinum-based therapy after progression on or after EGFR TKI. * Measurable disease per RECIST 1.1 as assessed by the local site investigator. * Archival tumor tissue sample or newly obtained core, incisional, or excisional biopsy of a tumor lesion not previously irradiated has been provided * Participants who have 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 HBV antiviral therapy for at least 4 weeks, and have undetectable HBV viral load prior to randomization. * Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy. * Have an ECOG performance status of 0 or 1 within 3 days before randomization.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) of Participants with NSCLC with Epidermal Growth Factor Receptor (EGFR) Mutations | Up to approximately 41 months | OS is defined as the time from randomization to death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| OS of All Participants with NSCLC | Up to approximately 41 months | OS is defined as the time from randomization to death due to any cause. |
| Progression-free Survival (PFS) of Participants with NSCLC with EGFR Mutations | Up to approximately 41 months | 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. |
| PFS of All Participants with NSCLC | Up to approximately 41 months | 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. |
| Objective Response Rate (ORR) of Participants with NSCLC with EGFR Mutations | Up to approximately 35 months | ORR was defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) as assessed using RECIST 1.1. based on BICR in NSCLC with EGFR mutations. |
| ORR of All Participants with NSCLC | Up to approximately 35 months | ORR was defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) as assessed using RECIST 1.1. based on BICR in all participants with NSCLC. |
| Duration of Response (DOR) of All Participants with NSCLC | Up to approximately 6 years | For participants who demonstrate confirmed CR or PR per RECIST 1.1 as assessed by BICR in all participants with NSCLC, DOR 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. |
| Change in Score from Baseline in Global Health Status/QoL Score (European Organisation for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire-Core 30 [QLQ-C30] Items 29 and 30) | Baseline and up to approximately 48 weeks | The EORTC QLQ-C30 is a questionnaire to assess the overall health status and quality of life of cancer patients. Participant responses to the questions "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). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status and quality of life. The change from baseline in EORTC QLQ-C30 Items 29 and 30 combined score will be presented. |
| Change in Score from Baseline in Dyspnea Score (EORTC QLQ-C30 Item 8) | Baseline and up to approximately 48 weeks | 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. The change from baseline in the dyspnea (EORTC QLQ-C30 Item 8) score will be presented. |
| Change in Score from Baseline in Cough (EORTC Quality of Life Questionnaire-Lung Cancer 13 [QLQ-LC13] Item 31) | Baseline and up to approximately 48 weeks | The EORTC QLQ-LC13 is a lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQ-C30. Participant responses to the question "How much did you cough?" 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 cough (EORTC QLQ-LC13 Item 31) score will be presented. A lower score indicates a better outcome. |
| Change in Score from Baseline in Chest Pain (EORTC QLQ-LC13 Item 40) | Baseline and up to approximately 48 weeks | 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. |
| Time to Deterioration (TTD) from Baseline in Global Health Status/QoL Score (EORTC QLQ-C30 Items 29 and 30) | Up to approximately 48 weeks | The EORTC QLQ-C30 is a questionnaire to assess the overall health status and quality of life of cancer patients. Participant responses to the questions "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). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status and quality of life. TTD is defined as the time to first onset of 10 or more (out of 100) deterioration from baseline and confirmed by a second adjacent 10 or more deterioration from baseline. TTD in the score of EORTC QLQ-C30 Items 29 and 30 will be presented. |
| TTD from Baseline in Dyspnea Score (EORTC QLQ-C30 Item 8) | Up to approximately 48 weeks | The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life of cancer patients. Participant responses to the question "Were you short of breath?" will be scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores will be standardized, so that scores range from 0 to 100. Higher scores indicates a worse level of dyspnea. TTD is defined as the time to first onset of 10 or more (out of 100) deterioration from baseline and confirmed by a second adjacent 10 or more deterioration from baseline. TTD in the score of EORTC QLQ-C30 Item 8 will be presented. |
| TTD from Baseline in Cough (EORTC Quality of Life Questionnaire-Lung Cancer 13 [QLQ-LC13] Item 31) | Up to approximately 48 weeks | The EORTC QLQ-LC13 is a lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQ-C30. Participant responses to the question "How much did you cough?" will be 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. Higher scores indicate more frequent coughing and a worse outcome. TTD is defined as the time to first onset of 10 or more (out of 100) deterioration from baseline and confirmed by a second adjacent 10 or more deterioration from baseline. TTD in the score of EORTC QLQ-LC13 Item 31 will be presented. |
| Time to Deterioration from Baseline in Chest Pain (EORTC QLQ-LC13 Item 40) | Up to approximately 48 weeks | 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. Higher scores indicate worse level of chest pain. TTD is defined as the time to first onset of 10 or more (out of 100) deterioration from baseline and confirmed by a second adjacent 10 or more deterioration from baseline. TTD in the score of EORTC QLQ-LC13 Item 40 will be presented. |
| Number of Participants Who Experience One or More Adverse Events (AEs) | Up to approximately 6 years | An AE is defined as 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. |
| Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) | Up to approximately 4 years | An AE is defined as 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. |
Countries
Australia, Brazil, Canada, Chile, China, Czechia, France, Germany, Greece, Hong Kong, Israel, Italy, Japan, Malaysia, Mexico, Philippines, Poland, South Korea, Spain, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States, Vietnam
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed