Non-small Cell Lung Cancer (NSCLC)
Conditions
Brief summary
The purpose of this study is to evaluate sacituzumab tirumotecan versus pemetrexed in combination with carboplatin for the treatment of epidermal growth factor receptor (EGFR)-mutated advanced non-squamous non-small cell lung cancer (NSCLC). Participants in this study have NSCLC that has continued to progress on prior treatment with EGFR tyrosine kinase inhibitors (TKIs). The primary hypotheses of this study are that sacituzumab tirumotecan is better than platinum-based doublet chemotherapy (pemetrexed and carboplatin) in regard to progression-free survival (PFS) and overall survival (OS).
Detailed description
Participants will be randomized 1:1 into two arms: * Sacituzumab tirumotecan * Pemetrexed plus Carboplatin Participants will receive treatment until any of the criteria for discontinuation of study intervention are met.
Interventions
BIOLOGICALSacituzumab tirumotecan
4 mg/kg via IV infusion
DRUGPemetrexed
500 mg/m\^2 via IV infusion
DRUGCarboplatin
AUC 5 mg/mL\*min via IV infusion
Administered as rescue medication per approved product label
Administered as rescue medication per approved product label
Administered as rescue medication per approved product label
Administered as rescue medication per approved product label
Administered as rescue medication per approved product label
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Unblinded Open-label
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed diagnosis of advanced-stage nonsquamous non-small cell lung cancer (NSCLC). * Participants who have adverse events (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 Hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load. * Participants with history of Hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable. * Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy. * Life expectancy of at least 3 months.
Exclusion criteria
* Predominantly squamous cell histology NSCLC. * History of second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 3 years. * Grade ≥2 peripheral neuropathy. * History of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing. * Active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease. * Uncontrolled, or significant cardiovascular disease or cerebrovascular disease. * 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 is allowed. * Received radiation therapy to the lung that is \>30 Gray within 6 months of the first dose of study intervention. * Known active central nervous system metastases and/or carcinomatous meningitis. * Active infection requiring systemic therapy. * History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease. * HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease. * Concurrent active HBV and HCV infection. * History of allogeneic tissue/solid organ transplant. * Participants who have not adequately recovered from major surgery or have ongoing surgical complications.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | Up to approximately 51 months | Progression-Free Survival is defined as the time from randomization to the first documented disease progression per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) based on blinded independent central review (BICR) or death due to any cause, whichever occurs first. PFS for all randomized participants will be reported. |
| Overall Survival (OS) | Up to approximately 51 months | Overall survival is defined as the time from randomization to death due to any cause. Overall survival for all randomized participants will be reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Up to approximately 51 months | The objective response rate (ORR) is defined as a confirmed complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by BICR. The overall response rate for all randomized participants will be reported. |
| Duration of Response (DOR) | Up to approximately 51 months | 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. CR is defined as the disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of diameters of target lesions. |
| Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score | Baseline and up to approximately 6 years | The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to the Global Health Status (GHS) question "How would you rate your overall health during the past week?" (Item 29) and the Quality of Life (QoL) question "How would you rate your overall quality of life during the past week?" (Item 30) 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 value indicates a better level of function. The change from baseline in EORTC QLQ-C30 Items 29 and 30 combined score will be reported. |
| Change From Baseline in the Dyspnea (Item 8) Score, on the EORTC QLQ-C30 | Baseline and up to approximately 6 years | The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to the question "Were you short of breath?" 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. A higher value indicates increased severity of symptoms. Change from baseline in dyspnea (EORTC QLQ-C30 Item 8) will be reported. |
| Change from Baseline in the Cough (Item 31) Score, on the EORTC Lung-Cancer specific Quality of Life Questionnaire (QLQ-LC13) | Baseline and up to approximately 6 years | 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. A higher value indicates increased severity of symptoms. Change from baseline in cough (EORTC QLQ-LC13 Item 31) will be reported. |
| Change from Baseline in the Chest Pain (Item 40) Score, on the EORTC QLQ-LC13 | Baseline and up to approximately 6 years | 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. A higher value indicates increased severity of symptoms. Change from baseline in chest pain (EORTC QLQ-LC13 Item 40) score will be presented. |
| Time to Deterioration (TTD) in Global Health Status/Quality of Life (Items 29 and 30) Combined Score, on the EORTC QLQ-C30 | Baseline and up to approximately 6 years | EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the QoL 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). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. TTD in Global Health Status (GHS)/Quality of Life (QoL) is defined as the time from baseline to the first onset of a ≥10-point decrease from baseline in combined GHS/QoL score. The TTD in GHS/QoL (Items 29 and 30) combined score will be reported. |
| TTD in the Dyspnea (Item 8) Score, on the EORTC QLQ-C30 | Baseline and up to approximately 6 years | EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the QoL of cancer patients. Participant responses to the question for Item 8 "Were you short of breath?" are scored on a 4-point scale (1=Not at All to 4=Very Much). TTD is defined as the time from baseline to the first onset of a ≥10-point decrease from baseline in score. The TTD in dyspnea score (EORTC QLQ-C30 Item 8) will be reported. |
| TTD in the Cough (Item 31) Score, on the EORTC QLQ-LC13 | Baseline and up to approximately 6 years | The EORTC QLQ-LC13 is a lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQ-C30. Participant responses to the question for Item 31 "How much did you cough?" are scored on a 4-point scale (1=Not at All to 4=Very Much). TTD is defined as the time from baseline to the first onset of a ≥10-point decrease from baseline in score. The TTD in cough score (EORTC QLQ-C30 Item 31) will be reported. |
| TTD in the Chest Pain (Item 40) Score, on the EORTC QLQ-LC13 | Baseline and up to approximately 6 years | The EORTC QLQ-LC13 is a lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQ-C30. Participant responses to the question for Item 40 "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. TTD is defined as the time from baseline to the first onset of a ≥10-point decrease from baseline in score. The TTD in chest pain score (EORTC QLQ-C30 Item 40) will be reported. |
| Number of Participants Who Experience One or More Adverse Events (AEs) | Up to approximately 6 years | 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. The number of participants who experience one or more AEs will be reported. |
| Number of Participants Who Discontinue Study Treatment Due to an AE | Up to approximately 6 years | 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. The number of participants who discontinue study treatment due to an AE will be reported. |
Countries
Argentina, Canada, China, Colombia, France, India, Italy, Japan, Malaysia, Mexico, Poland, South Korea, Spain, Sweden, Taiwan, Thailand, Turkey (Türkiye), United States, Vietnam
Contacts
CONTACTToll Free Number
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed