A Study of Rovalpituzumab Tesirine as Maintenance Therapy Following First- Line Platinum-Based Chemotherapy in Participants With Extensive Stage Small Cell Lung Cancer (MERU)

Study Overview
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Brief Summary
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This is a Phase 3, randomized, double-blind, placebo-controlled, multinational, and multicenter study to evaluate the efficacy of rovalpituzumab tesirine as maintenance therapy following first-line platinum-based chemotherapy.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of Rovalpituzumab Tesirine as Maintenance Therapy Following First-Line Platinum-Based Chemotherapy in Subjects With Extensive Stage Small Cell Lung Cancer (MERU)

Conditions
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Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Placebo for dexamethasone
* Drug: Placebo for rovalpituzumab tesirine
* Drug: Rovalpituzumab tesirine
* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed extensive-stage disease small cell lung cancer (ED SCLC) at initial diagnosis with ongoing clinical benefit (stable disease [SD], partial response [PR], or complete response [CR]) following completion of 4 cycles of first-line platinum-based therapy Participant is eligible to be randomized at least 3 but no more than 9 weeks from Day 1 of the fourth cycle of first-line platinum-based chemotherapy. Participants with a history of central nervous system (CNS) metastases prior to the initiation of first-line platinum-based chemotherapy must have received definitive local treatment and have documentation of stable or improved CNS disease status Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1 Participants must have adequate bone marrow, renal and hepatic function Availability of archived or representative tumor material for assessment of DLL3 expression Exclusion Criteria: Any prior systemic chemotherapy, small molecule inhibitors, immune checkpoint inhibitors, other monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, T-cell or other cell-based or biologic therapies, or any other anti-cancer therapy than that described in inclusion criteria for SCLC. Any disease-directed radiotherapy (except prophylactic cranial irradiation, palliative radiotherapy to a radiographically documented non-progressing lesion for symptom control, or pre-planned radiotherapy for CNS metastases present prior to start of first-line therapy and non-progressing) after last dose of first-line chemotherapy. Prior exposure to a pyrrolobenzodiazepine (PBD-based) or indolinobenzodiazepine-based drug, prior participation in a rovalpituzumab tesirine clinical trial, or known hypersensitivity or other contraindications to rovalpituzumab tesirine or excipient contained in the drug formulation.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rovalpituzumab tesirine/dexamethasone<br>Rovalpituzumab tesirine/dexamethasone every 6 weeks (q6 wk); omitting every third cycle | Drug: Rovalpituzumab tesirine<br>* Rovalpituzumab tesirine 0.3 mg/kg administered intravenously Day 1 of each 6-week cycle, omitting every third cycle<br>Drug: Dexamethasone<br>* Dexamethasone 8 mg administered orally (PO) twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6 week cycle, omitting every third cycle.<br>|
| Experimental: Placebo<br>Placebo q6 wk; omitting every third cycle | Drug: Placebo for dexamethasone<br>* Placebo for dexamethasone PO twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6 week cycle, omitting every third cycle.<br>Drug: Placebo for rovalpituzumab tesirine<br>* Placebo for rovalpituzumab tesirine administered intravenously Day 1 of each 6-week cycle, omitting every third cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) in Participants With Extensive-Stage Small Cell Lung Cancer With Delta-Like Protein 3 High Expression in Tumor (DLL3high) | OS is defined as the number of months from randomization to death of any cause. Calculated using the Kaplan-Meier methodology. | Survival follow-up continued until the endpoint of death, participant was lost to follow-up or withdrew consent, or termination of the study by AbbVie, whichever occurred first. Median time on study overall was 11.9 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OS in All Randomized Participants | OS is defined as the number of months from randomization to death of any cause. Calculated using the Kaplan-Meier methodology. | Survival follow-up continued until the endpoint of death, the subject was lost to follow-up or withdrew consent, or termination of the study by AbbVie, whichever occurred first. Median time on study overall was 11.9 months. | 
| Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30) Physical Functioning Domain Over Time | The EORTC QLQ-C30 is composed of global health status/QoL scale; five functional domains (physical, role, emotional, cognitive, and social); three symptom domains (fatigue, nausea and vomiting, and pain); and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The Physical Functioning domain includes 5 questions in which participants were asked to rate their overall health and overall quality of life as it relates to physical functioning during the past week on a scale from 1 (very poor) to 7 (excellent). The 5 scores were averaged and transformed to a scale from 0 to 100, where a high score represents a high QoL. A positive change from baseline indicates better quality of life. | Baseline, Weeks 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, Final Visit (up to Week 78) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Extensive-Stage Small Cell Lung Cancer (ED SCLC), Cancer, Platinum-Based Chemotherapy, Rovalpituzumab tesirine, first-line chemotherapy, Small Cell Lung Cancer (SCLC), Delta-like protein 3 (DLL3)