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) Who Have Progressed on Prior EGFR Tyrosine Kinase Inhibitors (MK-2870-009)

Phase 3RecruitingNCT06305754

Merck Sharp & Dohme LLC520 enrolled

Overview

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).

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

520

Conditions

Non-small Cell Lung Cancer (NSCLC)

Interventions

4 mg/kg via IV infusion

PemetrexedDRUG

500 mg/m\^2 via IV infusion

CarboplatinDRUG

AUC 5 mg/mL\*min via IV infusion

H1 Receptor AntagonistDRUG

Administered as rescue medication per approved product label

H2 Receptor AntagonistDRUG

Administered as rescue medication per approved product label

Acetaminophen (or equivalent)DRUG

Administered as rescue medication per approved product label

Dexamethasone (or equivalent)DRUG

Administered as rescue medication per approved product label

Steroid Mouthwash (dexamethasone or equivalent)DRUG

Administered as rescue medication per approved product label

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (155)

Kaiser Permanente - Oakland ( Site 0054)

Oakland, California, United States

RECRUITING

Kaiser Permanente - Roseville ( Site 0055)

Roseville, California, United States

RECRUITING

Kaiser Permanente - San Francisco ( Site 0056)

San Francisco, California, United States

RECRUITING

Kaiser Permanente - Santa Clara ( Site 0057)

Santa Clara, California, United States

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: Up to approximately 51 months

Secondary Outcomes

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.

Time frame: 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.

Time frame: Up to approximately 51 months

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.