Sacituzumab Tirumotecan (MK-2870) Versus Pemetrexed and Carboplatin Combination Therapy in Participants With Epidermal Growth Factor (EGFR)-Mutated, Advanced Nonsquamous Non-small Cell Lung Cancer (NSCLC) and Have Progressed on Prior EGFR Tyrosine Kinase Inhibitors (MK-2870-009)

A Randomized, Open-label, Phase 3 Study of MK-2870 vs. Platinum Doublets in Participants With EGFR-mutated, Advanced Nonsquamous Non-small Cell Lung Cancer (NSCLC) Who Have Progressed on Prior EGFR Tyrosine Kinase Inhibitors

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Non-small Cell Lung Cancer (NSCLC)
• Intervention / Treatment: Drug: Antihistamine; Drug: H2 Receptor Antagonist; Drug: Acetaminophen (or equivalent); Drug: Dexamethasone (or equivalent); Drug: Pemetrexed; Drug: Carboplatin; Biological: Sacituzumab tirumotecan

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.

• Study Type: Interventional
• Enrollment (Estimated): 520
• 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 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 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Pemetrexed Plus Carboplatin; Participants receive, via IV infusion, 500 mg/m2 pemetrexed every 3 weeks (Days 1 and 22 of every 6-week cycle) plus area under the curve (AUC) 5 mg/mL*min carboplatin every 3 weeks (Days 1 and 22 of every 6-week cycle for 4 doses), then 500 mg/m2 pemetrexed every 3 weeks until discontinuation criteria is met.	Drug: Pemetrexed; 500 mg/m^2 via IV infusion; Drug: Carboplatin; AUC 5 mg/mL*min via IV infusion
Experimental: Sacituzumab tirumotecan; Participants receive 4 mg/kg sacituzumab tirumotecan via intravenous (IV) infusion every 2 weeks (Days 1, 15, and 29 of every 6-week cycle) until discontinuation criteria is met.	Drug: Antihistamine; Administered as rescue medication per approved product label; Drug: H2 Receptor Antagonist; Administered as rescue medication per approved product label; Drug: Acetaminophen (or equivalent); Administered as rescue medication per approved product label; Drug: Dexamethasone (or equivalent); Administered as rescue medication per approved product label; Biological: Sacituzumab tirumotecan; 4 mg/kg via IV infusion; Other Names: SKB264; MK-2870

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	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.	Up to approximately 51 months
Overall Survival (OS)	Overall survival is defined as the time from randomization to death due to any cause. Overall survival for all randomized participants will be reported.	Up to approximately 51 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	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.	Up to approximately 51 months
Duration of Response (DOR)	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.	Up to approximately 51 months
Change From Baseline in the Dyspnea (Item 8) Score, on the EORTC QLQ-C30	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.	Baseline and up to approximately 6 years
Change from Baseline in the Cough (Item 31) Score, on the EORTC Lung-Cancer specific Quality of Life Questionnaire (QLQ-LC13)	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.	Baseline and up to approximately 6 years
Change from Baseline in the Chest Pain (Item 40) Score, on the EORTC QLQ-LC13	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.	Baseline and up to approximately 6 years
TTD in the Dyspnea (Item 8) Score, on the EORTC QLQ-C30	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.	Baseline and up to approximately 6 years
TTD in the Cough (Item 31) Score, on the EORTC QLQ-LC13	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.	Baseline and up to approximately 6 years
TTD in the Chest Pain (Item 40) Score, on the EORTC QLQ-LC13	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.	Baseline and up to approximately 6 years
Number of Participants Who Experience One or More Adverse Events (AEs)	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.	Up to approximately 6 years
Number of Participants Who Discontinue Study Treatment Due to an 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. The number of participants who discontinue study treatment due to an AE will be reported.	Up to approximately 6 years
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	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.	Baseline and up to approximately 6 years
Time to Deterioration (TTD) in Global Health Status/Quality of Life (Items 29 and 30) Combined Score, on the EORTC QLQ-C30	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.	Baseline and up to approximately 6 years

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information.

Study record dates

Study Major Dates

• Study Start (Estimated): June 3, 2024
• Primary Completion (Estimated): September 12, 2028
• Study Completion (Estimated): June 14, 2030

Study Registration Dates

• First Submitted: March 5, 2024
• First Submitted That Met QC Criteria: March 5, 2024
• First Posted (Actual): March 12, 2024

Study Record Updates

• Last Update Posted (Actual): April 23, 2024
• Last Update Submitted That Met QC Criteria: April 22, 2024
• Last Verified: April 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; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antipyretics; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Histamine Agents; Folic Acid Antagonists; Dexamethasone; Carboplatin; Acetaminophen; Pemetrexed; Histamine H1 Antagonists; Histamine Antagonists; Histamine H2 Antagonists
• Other Study ID Numbers: 2870-009; 2023-504910-31 (Registry Identifier: EU CT); U1111-1288-3804 (Other Identifier: UTN); MK-2870-009 (Other Identifier: Merck)

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