Sacituzumab Tirumotecan (MK-2870) in Combination With Pembrolizumab Versus Pembrolizumab Alone in Metastatic Non-small Cell Lung Cancer (NSCLC) With Programmed Cell Death Ligand 1 (PD-L1) Tumor Proportion Score (TPS) ≥ 50% (MK-2870-007)

• ClinicalTrials.gov Identifier: NCT06170788
• Recruitment Status: Recruiting
• First Posted: December 14, 2023
• Last Update Posted: May 10, 2024
• Sponsor: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

Tracking Information

• First Submitted Date: December 3, 2023
• First Posted Date: December 14, 2023
• Last Update Posted Date: May 10, 2024
• Actual Study Start Date: December 15, 2023
• Estimated Primary Completion Date: January 25, 2028 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 6, 2023)

Overall Survival (OS) [ Time Frame: Up to approximately 48 months ]

OS is defined as the time from randomization to death from any cause.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 6, 2023)

• Progression free survival (PFS) [ Time Frame: Up to approximately 48 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 (OR) [ Time Frame: Up to approximately 48 months ]
  The OR is defined as a confirmed complete response (CR) or partial response (PR) per RECIST 1.1 as assessed by BICR.
• Duration of Response (DOR) [ Time Frame: Up to approximately 48 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.
• 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 [ Time Frame: Baseline and up to approximately 24 months ]
  Change from baseline in the score of EORTC QLQ-C30 Items 29 and 30 will be presented. The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life 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). A higher score indicates a better overall outcome.
• Change From Baseline in Dyspnea (EORTC QLQ-C30 Item 8) Score [ Time Frame: Baseline and up to approximately 24 months ]
  Change from baseline in the score of EORTC QLQ-C30 Item 8 will be presented. 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.
• Change From Baseline in Cough (EORTC QLQ-LC13 Item 31) Score [ Time Frame: Baseline and up to approximately 24 months ]
  Change from baseline in the score of EORTC QLQ-C13 Item 31 will be presented. The EORTC QLQ-C13 is a lung cancer specific health-related quality-of life (QoL) questionnaire. Participant response to the question "Have you coughed?" is scored on a 4-point scale (1=Not at All to 4=Very Much). A higher score indicates more frequent coughing.
• Change From Baseline in Chest Pain (EORTC QLQ-LC13 item 40) Score [ Time Frame: Baseline and up to approximately 24 months ]
  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) Based on Change From Baseline in Global Health Status (GHS)/ QOL Score (EORTC QLQ-C30 Item 29 and 30) [ Time Frame: Up to approximately 24 months ]
  The TTD in GHS/QOL score (EORTC QLQ-C30 Items 29 and 30) will be presented. 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). A higher score indicates a better overall outcome. TTD as assessed based on a negative change (decrease in score) from Baseline in GHS/QOL score. A longer TTD indicates a better outcome.
• Time to Deterioration (TTD) Based on Change From Baseline in Dyspnea Score (EORTC QLQ-C30 Item 8) [ Time Frame: Up to approximately 24 months ]
  The TTD in Dyspnea score (EORTC QLQ-C30 Item 8) will be presented. 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. TTD is assessed based on the time to a negative change (increase in score) from baseline. A longer TTD indicates a better outcome.
• Time to Deterioration (TTD) Based on Change From Baseline in Cough Score (EORTC QLQ-LC13 Item 31). [ Time Frame: Up to approximately 24 months ]
  The TTD in Cough score (EORTC QLQ-LC13 Item 31) will be presented. Participant response to the question "Have you coughed?" is scored on a 4-point scale (1=Not at All to 4=Very Much). A higher score indicates more frequent coughing. TTD is assessed based on the time to a negative change (increase in score) from baseline. A longer TTD indicates a better outcome.
• Time to Deterioration (TTD) Based on Change From Baseline in Chest Pain Score (EORTC QLQ-LC13 Item 40) [ Time Frame: Up to approximately 24 months ]
  The TTD in Chest Pain score (EORTC QLQ-LC13 Item 40) will be presented. Participant response to the question "Have you had pain in your chest?" is scored on a 4-point scale (1=Not at All to 4=Very Much). A higher score indicates a worse level of chest pain. TTD is assessed based on the time to a negative change (increase in score) from baseline. A longer TTD indicates a better outcome.
• Percentage of Participants That Experience at Least 1 Adverse Event [ Time Frame: Up to approximately 27 months ]
  An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The percentage of participants who experience an AE will be presented.
• Percentage of Participants Who Discontinue Study Treatment Due to an AE [ Time Frame: Up to approximately 24 months ]
  The percentage of participants who discontinue study treatment due to an AE will be presented.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Sacituzumab Tirumotecan (MK-2870) in Combination With Pembrolizumab Versus Pembrolizumab Alone in Metastatic Non-small Cell Lung Cancer (NSCLC) With Programmed Cell Death Ligand 1 (PD-L1) Tumor Proportion Score (TPS) ≥ 50% (MK-2870-007)
• Official Title: 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%

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.

All participants who have completed the first course of pembrolizumab may be eligible for up to an additional 9 cycles of pembrolizumab monotherapy if there is blinded independent central review (BICR)-verified progressive disease by Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) after initial treatment.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Treatment
• Condition: Non-small Cell Lung Cancer (NSCLC)

Intervention

• Biological: Sacituzumab tirumotecan
  IV infusion
  Other Names:

  • SKB264
  • MK-2870
• Biological: Pembrolizumab
  IV infusion
  Other Names:

  • MK-3475
  • KEYTRUDA®
  • SCH 900475

Study Arms

• Experimental: 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.
  Interventions:

  • Biological: Sacituzumab tirumotecan
  • Biological: Pembrolizumab
• Active Comparator: Pembrolizumab
  Participants receive 400 mg Pembrolizumab via IV infusion q6w on Day 1 of each 6-week cycle for 18 cycles
  Intervention: Biological: Pembrolizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: December 6, 2023): 614
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 27, 2030
• Estimated Primary Completion Date: January 25, 2028 (Final data collection date for primary outcome measure)

Eligibility Criteria

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 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Toll Free Number; 1-888-577-8839; Trialsites@merck.com

• Listed Location Countries: Australia, Chile, Denmark, France, Spain, Taiwan, Turkey, United States

Administrative Information

• NCT Number: NCT06170788
• Other Study ID Numbers: 2870-007; MK-2870-007 ( Other Identifier: Merck ); 2023-503376-24-00 ( Other Identifier: European Union )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

• Current Responsible Party: Merck Sharp & Dohme LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Merck Sharp & Dohme LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme LLC

• PRS Account: Merck Sharp & Dohme LLC
• Verification Date: May 2024