A Randomized, Open-label, Phase 3 Study of MK-2870 in Combination With Pembrolizumab Compared to Pembrolizumab Monotherapy in the First-line Treatment of Participants With Metastatic Non-small Cell Lung Cancer With PD-L1 TPS Greater Than or Equal to 50% (TroFuse-007)
Trial Snapshot
- Phase
- Phase 3
- Status
- Recruiting
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 614
- Locations
- 440
- Primary Endpoint
- Overall Survival (OS)
Study Overview
Brief Summary
The primary objective of the study is to compare sacituzumab tirumotecan combined with pembrolizumab to pembrolizumab alone with respect to overall survival (OS). The primary hypothesis is that the combination of sacituzumab tirumotecan and pembrolizumab is superior to pembrolizumab alone with respect to OS.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Single (Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Histologically or cytologically confirmed diagnosis of squamous or nonsquamous NSCLC
- •Confirmation that epidermal growth factor receptor- (EGFR-), anaplastic lymphoma kinase- (ALK-), or proto-oncogene tyrosine-protein kinase ROS (ROS1-) directed therapy is not indicated as primary therapy
- •Provided tumor tissue that demonstrates programmed cell death ligand 1 (PD-L1) expression in ≥50% of tumor cells as assessed by an immunohistochemistry (IHC) central laboratory
- •An Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 7 days before randomization.
- •A life expectancy of at least 3 months.
- •Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART)
Exclusion Criteria
- •Diagnosis of small cell lung cancer or, for mixed tumors, presence of small cell elements.
- •Has 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.
- •Has active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, or chronic diarrhea).
- •Has uncontrolled, significant cardiovascular disease or cerebrovascular disease within the 6 months preceding study intervention.
- •Received prior systemic anticancer therapy for their metastatic NSCLC.
- •Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor Note: Prior treatment with an anti-PD-1, anti-PD- L1, or anti-PD-L2 agent in the neoadjuvant or adjuvant setting for nonmetastatic resectable NSCLC is allowed as long as therapy was completed at least 12 months before diagnosis of metastatic NSCLC.
- •Received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization.
- •Received radiation therapy to the lung that is >30 Gy within 6 months of start of study intervention.
- •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 are allowed.
- •Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
- •Known additional malignancy that is progressing or has required active treatment within the past 3 years.
- •Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- •Known intolerance to sacituzumab tirumotecan or pembrolizumab and/or any of their excipients; for pembrolizumab, severe hypersensitivity (≥Grade 3) is exclusionary.
- •Known hypersensitivity to sacituzumab tirumotecan or other biologic therapy.
- •Active autoimmune disease that has required systemic treatment in the past 2 years.
- •History of (noninfectious) pneumonitis/interstitial lung disease (ILD) that required steroids or has current pneumonitis/ILD.
- •Active infection requiring systemic therapy
- •Concurrent active Hepatitis B and Hepatitis C virus infection.
- •Human immunodeficiency virus (HIV)-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
- •History of allogeneic tissue/solid organ transplant.
- •Requires treatment with a strong inhibitor or inducer of Cytochrome P450 3A4 (CYP3A4) at least 14 days before the first dose of study intervention and throughout the study.
Arms & Interventions
Pembrolizumab + Sacituzumab tirumotecan
Participants receive sacituzumab tirumotecan via intravenous (IV) infusion on Days 1, 15 and 29 of each 6-week cycle + 400 mg Pembrolizumab every 6 weeks (q6w) via IV infusion on Day 1 of each 6-week cycle for 18 cycles. Additionally, participants receive diphenhydramine (or equivalent), an H2 antagonist of investigator's choice, acetaminophen (or equivalent), and dexamethasone (or equivalent) per each drug's product label prior to the first 4 infusions of sacituzumab tirumotecan. At subsequent infusions, the H2 antagonist and dexamethasone are optional, at the discretion of the investigator.
Intervention: Sacituzumab tirumotecan (Biological)
Pembrolizumab + Sacituzumab tirumotecan
Participants receive sacituzumab tirumotecan via intravenous (IV) infusion on Days 1, 15 and 29 of each 6-week cycle + 400 mg Pembrolizumab every 6 weeks (q6w) via IV infusion on Day 1 of each 6-week cycle for 18 cycles. Additionally, participants receive diphenhydramine (or equivalent), an H2 antagonist of investigator's choice, acetaminophen (or equivalent), and dexamethasone (or equivalent) per each drug's product label prior to the first 4 infusions of sacituzumab tirumotecan. At subsequent infusions, the H2 antagonist and dexamethasone are optional, at the discretion of the investigator.
Intervention: Pembrolizumab (Biological)
Pembrolizumab
Participants receive 400 mg Pembrolizumab via IV infusion q6w on Day 1 of each 6-week cycle for 18 cycles
Intervention: Supportive care measures (Drug)
Pembrolizumab
Participants receive 400 mg Pembrolizumab via IV infusion q6w on Day 1 of each 6-week cycle for 18 cycles
Intervention: Pembrolizumab (Biological)
Pembrolizumab + Sacituzumab tirumotecan
Participants receive sacituzumab tirumotecan via intravenous (IV) infusion on Days 1, 15 and 29 of each 6-week cycle + 400 mg Pembrolizumab every 6 weeks (q6w) via IV infusion on Day 1 of each 6-week cycle for 18 cycles. Additionally, participants receive diphenhydramine (or equivalent), an H2 antagonist of investigator's choice, acetaminophen (or equivalent), and dexamethasone (or equivalent) per each drug's product label prior to the first 4 infusions of sacituzumab tirumotecan. At subsequent infusions, the H2 antagonist and dexamethasone are optional, at the discretion of the investigator.
Intervention: Supportive care measures (Drug)
Outcomes
Primary Outcomes
Overall Survival (OS)
Time Frame: Up to approximately 49 months
OS is defined as the time from randomization to death from any cause.
Secondary Outcomes
- Percentage of Participants Who Discontinue Study Treatment Due to an AE(Up to approximately 77 months)
- Percentage of Participants That Experience at Least 1 Adverse Event(Up to approximately 77 months)
- Change from Baseline in Global Health Status/Quality of Life (QOL) [European Organisation for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30) 29 Items and 30] Score(Baseline and up to approximately 77 months)
- Change From Baseline in Dyspnea (EORTC QLQ-C30 Item 8) Score(Baseline and up to approximately 77 months)
- Change From Baseline in Cough (EORTC QLQ-LC13 Item 31) Score(Baseline and up to approximately 77 months)
- Change From Baseline in Chest Pain (EORTC QLQ-LC13 item 40) Score(Baseline and up to approximately 77 months)
- Time to Deterioration (TTD) Based on Change From Baseline in Global Health Status (GHS)/ QOL Score (EORTC QLQ-C30 Item 29 and 30)(Up to approximately 77 months)
- Time to Deterioration (TTD) Based on Change From Baseline in Dyspnea Score (EORTC QLQ-C30 Item 8)(Up to approximately 77 months)
- Time to Deterioration (TTD) Based on Change From Baseline in Cough Score (EORTC QLQ-LC13 Item 31).(Up to approximately 77 months)
- Time to Deterioration (TTD) Based on Change From Baseline in Chest Pain Score (EORTC QLQ-LC13 Item 40)(Up to approximately 77 months)
- Progression free survival (PFS)(Up to approximately 77 months)
- Duration of Response (DOR)(Up to approximately 77 months)
- Change from Baseline in Global Health Status/Quality of Life (QOL) [European Organisation for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30) 29 Items and 30] Score(Baseline and up to approximately 77 months)
- Change From Baseline in Dyspnea (EORTC QLQ-C30 Item 8) Score(Baseline and up to approximately 77 months)
- Change From Baseline in Cough (EORTC QLQ-LC13 Item 31) Score(Baseline and up to approximately 77 months)
- Change From Baseline in Chest Pain (EORTC QLQ-LC13 item 40) Score(Baseline and up to approximately 77 months)
- Time to Deterioration (TTD) Based on Change From Baseline in Global Health Status (GHS)/ QOL Score (EORTC QLQ-C30 Item 29 and 30)(Up to approximately 77 months)
- Time to Deterioration (TTD) Based on Change From Baseline in Dyspnea Score (EORTC QLQ-C30 Item 8)(Up to approximately 77 months)
- Time to Deterioration (TTD) Based on Change From Baseline in Cough Score (EORTC QLQ-LC13 Item 31).(Up to approximately 77 months)
- Time to Deterioration (TTD) Based on Change From Baseline in Chest Pain Score (EORTC QLQ-LC13 Item 40)(Up to approximately 77 months)
- Percentage of Participants That Experience at Least 1 Adverse Event(Up to approximately 77 months)
- Percentage of Participants Who Discontinue Study Treatment Due to an AE(Up to approximately 77 months)
- Progression free survival (PFS)(Up to approximately 49 months)
- Objective Response (OR)(Up to approximately 49 months)
- Duration of Response (DOR)(Up to approximately 49 months)