Pembrolizumab With or Without Maintenance Sacituzumab Tirumotecan (Sac-TMT; MK-2870) in Metastatic Squamous Non-small Cell Lung Cancer (NSCLC) [MK-2870-023]

Phase 3 Study of Pembrolizumab in Combination With Carboplatin/Taxane (Paclitaxel or Nab-paclitaxel) Followed by Pembrolizumab With or Without Maintenance MK-2870 in the First-line Treatment of Metastatic Squamous Non-small Cell Lung Cancer

This is a phase 3 study of pembrolizumab in combination with carboplatin/taxane (paclitaxel or nab-paclitaxel) followed by pembrolizumab with or without maintenance sacituzumab tirumotecan (sac-TMT; MK-2870) in first-line treatment of metastatic squamous non-small cell lung cancer. It is hypothesized that pembrolizumab with maintenance sacituzumab tirumotecan is superior to pembrolizumab without sacituzumab tirumotecan maintenance with respect to overall survival (OS).

Study Overview

• Status: Not yet recruiting
• Conditions: NSCLC; Non-small Cell Lung Cancer
• Intervention / Treatment: Biological: Pembrolizumab; Biological: sac-TMT

Detailed Description

All participants undergo an initial induction phase of four cycles, each cycle consisting of a 3-week cycle of pembrolizumab q3w + carboplatin q3w + paclitaxel q3w or nabpaclitaxel weekly. Participants are then randomly assigned to pembrolizumab maintenance vs. pembrolizumab + sac-TMT maintenance.

• Study Type: Interventional
• Enrollment (Estimated): 851
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of squamous squamous non-small cell lung cancer (NSCLC) [Stage IV: M1a, M1b, M1c, American Joint Committee on Cancer Staging Manual, version 8]
• Measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology
• Has life expectancy ≥3 months
• Has Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1 assessed within 7 days prior to allocation
• Archival tumor tissue sample or newly obtained core, incisional, or excisional biopsy of a tumor lesion not previously irradiated has been provided
• 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 before allocation
• Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening
• Participants who have adverse events (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)
• Has adequate organ function
• For Maintenance only (prior to randomization): is without disease progression of their NSCLC, as determined by BICR using RECIST 1.1 after completion of study-specified Induction with an evaluable scan at Week 12
• For Maintenance only (prior to randomization): has ECOG PS of 0 or 1 as assessed at the Prerandomization Visit
• For Maintenance only (prior to randomization): all AEs (with the exception of alopecia, Grade 2 fatigue, and Grade ≤2 endocrine-related AEs requiring treatment or hormone replacement) have recovered
• For Maintenance only (prior to randomization): has adequate organ function

Exclusion Criteria:

• Diagnosis of small cell lung cancer or, for mixed tumors, presence of small cell elements
• 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
• Active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease
• Has uncontrolled, significant cardiovascular disease or cerebrovascular disease including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, uncontrolled symptomatic arrhythmia, prolongation of QTcF interval to >480 ms, and other serious cardiovascular and cerebrovascular diseases within 6 months before study intervention
• HIV-infected participants who have been newly diagnosed or with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
• 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 (eg, cytotoxic Tlymphocyte-associated protein 4, OX-40, CD137) [Note: Prior treatment with chemotherapy and/or radiation as a part of neoadjuvant or adjuvant therapy or chemoradiation therapy for nonmetastatic NSCLC is allowed as long as therapy was completed at least 12 months before diagnosis of metastatic NSCLC.]
• Received prior treatment with a TROP2-targeted antidrug conjugate (ADC)
• Received prior systemic anticancer therapy including investigational agents within 4 weeks before allocation
• Received radiation therapy to the lung that is >30 Gray 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
• Active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease
• Participants who have not adequately recovered from major surgery or have ongoing surgical complications
• Received prior treatment with a topoisomerase I inhibitor-containing ADC
• Is currently receiving a strong inducer/inhibitor of CYP3A4 that cannot be discontinued for the duration of the study (the required washout period before starting sac-TMT is 2 weeks)
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
• Has known CNS metastases/carcinomatous meningitis (participants with previously treated brain metastases may participate provided they are clinically stable for t least 2 weeks and, have no evidence of new or enlarging brain metastases and also are off steroids 3 days prior to dosing with study medication. Subjects with known untreated, asymptomatic brain metastases [ie, no neurological symptoms, no requirements for corticosteroids, no or minimal surrounding edema, and no lesion >1.5 cm] may participate but will require regular imaging of the brain as a site of disease)
• Severe hypersensitivity (≥Grade 3) to study intervention and/or any of its excipients or to another biologic therapy
• Active autoimmune disease that has required systemic treatment in the past 2 years (replacement therapy [eg, thyroxine, insulin, or physiologic corticosteroid] is allowed)
• History of (noninfectious)pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
• Active infection requiring systemic therapy
• History of allogeneic tissue/solid organ transplant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Maintenance Arm 1: Pembrolizumab + sac-TMT; During the Induction phase, participants receive pembrolizumab 200 mg q3w for 4 cycles, carboplatin AUC 6 (mg/mL/min) q3w for 4 cycles, and paclitaxel 200 mg/m2 q3w for 4 cycles or nab-paclitaxel 100 mg/m2 weekly for 4 cycles. During the Maintenance phase, participants receive sac-TMT 4 mg/kg infusion every 2 weeks (q2w) after receipt of an antihistamine, H2 receptor antagonist, acetaminophen (or equivalent), and dexamethasone (or equivalent) until discontinuation criteria is met for sac-TMT; and pembrolizumab 400 mg every 6 weeks (q6w) for 96 weeks.	Biological: Pembrolizumab; Intravenous (IV) infusion; Other Names: MK-3475; SCH 900475; KEYTRUDA®; Biological: sac-TMT; IV infusion; Other Names: MK-2870; Sacituzumab tirumotecan
Active Comparator: Maintenance Arm 2: Pembrolizumab Monotherapy; During the induction phase, participants receive pembrolizumab 200 mg q3w for 4 cycles, carboplatin AUC 6 (mg/mL/min) q3w for 4 cycles, and paclitaxel 200 mg/m2 q3w for 4 cycles or nab-paclitaxel 100 mg/m2 weekly for 4 cycles. During the Maintenance phase, participants receive pembrolizumab 400 mg q6w for 96 weeks.	Biological: Pembrolizumab; Intravenous (IV) infusion; Other Names: MK-3475; SCH 900475; KEYTRUDA®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	OS is the time from randomization to death due to any cause.	Up to ~79 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first as assessed by Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1).	Up to ~79 months
Number of participants with ≥1 adverse event (AE)	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.	Up to ~79 months
Number of participants discontinuing from study therapy due to AE(s)	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.	Up to ~79 months
Change in Score from Baseline to a Predefined Timepoint in Participant-Reported Global health status/Quality of Life (QoL) Score (EORTC QLQ-C30 Items 29 and 30)	European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) is a 30-item scale to assess the overall quality of life in cancer patients. The global health status and QoL scores are based on participant responses to items 29 ("How would you rate your overall health during past week?") and 30 ("How would you rate your overall quality of life during the week?") that are scored on a 7-point scale (1 = "Very poor" to 7 = "Excellent"). Higher scores indicate better overall health status.	Baseline and up to ~79 months
Change in Score from Baseline to a Predefined Timepoint in Participant-Reported Dyspnea (EORTC QLQ-C30 Item 8)	EORTC QLQ-C30 is a 30-item scale to assess the overall quality of life of cancer patients. The dyspnea score is based on participant responses to item 8 ("Were you short of breath?") that is scored on a 4-point scale (1 = 'Not at All' to 4 = 'Very Much'). Higher scores indicate worse dyspnea symptoms.	Baseline and up to ~79 months
Change in Score from Baseline to a Predefined Timepoint in Participant-Reported Cough (EORTC QLQ-LC13 Item 31)	EORTC QLQ-C13 is a 13-item addendum to EORTC QLQ-C30 to assess the overall quality of life of lung cancer patients. The cough score is based on participant responses to item 31 ("How much did you cough?") that is scored on a 4-point scale (1 = 'Not at All' to 4 = 'Very Much'). Higher scores indicate worse cough.	Baseline and up to ~79 months
Change in Score from Baseline to a Predefined Timepoint in Participant-Reported Chest Pain (EORTC QLQ-LC13 Item 40)	EORTC QLQ-C13 is a 13-item addendum to EORTC QLQ-C30 to assess the overall quality of life of lung cancer patients. The chest pain score is based on participant responses to item 40 e (1 = "Not at All" to 4 = "Very Much").	Baseline and up to ~79 months
Time to First Deterioration (TTD) in Global Health Status/QoL Scores (EORTC QLQ-C30 Items 29 and 30)	EORTC QLQ-C30 is a 30-item scale to assess the overall quality of life in cancer patients. TTD in global health status and QoL scores are based on participant responses to items 29 ("How would you rate your overall health during past week?") and 30 ("How would you rate your overall quality of life during the week?") that are scored on a 7-point scale (1 = "Very poor" to 7 = "Excellent"). Higher scores indicate better overall health status.	Up to ~79 months
TTD in Dyspnea Score (EORTC QLQ-C30 Item 8)	EORTC QLQ-C30 is a 30-item scale to assess the overall quality of life of cancer patients. TTD in dyspnea score is based on participant responses to item 8 ("Were you short of breath?") that is scored on a 4-point scale (1 = 'Not at All' to 4 = 'Very Much'). Higher scores indicate worse dyspnea symptoms.	Up to ~79 months
TTD in Cough (EORTC QLQ-LC13 Item 31)	EORTC QLQ-C13 is a 13-item addendum to EORTC QLQ-C30 to assess the overall quality of life of lung cancer patients. TTD in cough score is based on participant responses to item 31 ("How much did you cough?") that is scored on a 4-point scale (1 = 'Not at All' to 4 = 'Very Much'). Higher scores indicate worse cough.	Up to ~79 months
TTD in Chest Pain (EORTC QLQ-LC13 Item 40)	EORTC QLQ-C13 is a 13-item addendum to EORTC QLQ-C30 to assess the overall quality of life of lung cancer patients. TTD in chest pain score is based on participant responses to item 40 ("Have you had pain in your chest?") that is scored on a 4-point scale (1 = 'Not at All' to 4 = 'Very Much'). Higher scores indicate worse chest pain.	Up to ~79 months

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Estimated): July 2, 2024
• Primary Completion (Estimated): January 12, 2029
• Study Completion (Estimated): February 12, 2031

Study Registration Dates

• First Submitted: May 15, 2024
• First Submitted That Met QC Criteria: May 15, 2024
• First Posted (Actual): May 20, 2024

Study Record Updates

• Last Update Posted (Actual): May 20, 2024
• Last Update Submitted That Met QC Criteria: May 15, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: 2870-023; 2023-510128-66 (Other Identifier: EU CT); U1111-1301-2790 (Other Identifier: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No