Study Comparing Rovalpituzumab Tesirine Versus Topotecan in Subjects With Advanced or Metastatic Small Cell Lung Cancer With High Levels of Delta-like Protein 3 (DLL3) and Who Have First Disease Progression During or Following Front-line Platinum-based Chemotherapy (TAHOE)

AbbVie

Status and phase: Completed; Phase 3

Conditions: Small Cell Lung Cancer

Treatments: Drug: Rovalpituzumab tesirine; Drug: Dexamethasone; Drug: Topotecan

Study type: Interventional

Funder types: Industry

Identifiers

NCT03061812

2016-003726-17 (EudraCT Number)

M16-289

Details and patient eligibility

About

The purpose of this randomized, open-label, 2-arm, phase 3 study is to assess the efficacy, safety and tolerability of rovalpituzumab tesirine versus topotecan in participants with advanced or metastatic SCLC with high levels of DLL3, who have first disease progression during or following front-line platinum-based chemotherapy.

Enrollment: 444 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participant must have histologically or cytologically confirmed advanced or metastatic Small Cell Lung Cancer (SCLC) with documented first disease progression during or following front-line platinum-based systemic regimen
• Tumor must have high Delta-like protein 3 (DLL3) expression defined as having ≥ 75% tumor cells staining positive according to the VENTANA DLL3 (SP347) IHC Assay.
• Participant must have measurable disease, as defined per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
• Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Participant must have recovery to Grade 0 or 1 of any clinically significant toxicity (excluding alopecia) prior to initiation of study drug administration.

Exclusion criteria

• Participant has a documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms consistent with New York Heart Association Class (NYHA) III - IV within 6 months prior to their first dose of study drug.
• Participant has known leptomeningeal metastases.
• Participant has received more than one prior systemic therapy regimen for SCLC.
• Participant had a serious infection within 2 weeks prior to randomization, including any Grade 3 or higher viral, bacterial, or fungal infection.
• Participant has a history of active malignancies other than SCLC within the past 2 years prior to study entry, with the exception of in situ cancer which was curatively treated.
• Participant had prior exposure to topotecan, irinotecan or any other topoisomerase I inhibitors.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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444 participants in 2 patient groups

Rovalpituzumab tesirine

Experimental group

Description:

Rovalpituzumab tesirine IV administration (dosing based on actual body weight) on Day 1 of a 42-day cycle for 2 cycles, with up to 2 additional cycles permitted. Dexamethasone coadministered orally (PO) twice daily at a dose of 8 mg on Day -1, Day 1, and Day 2 of each 42-day cycle in which rovalpituzumab tesirine is administered.

Treatment:

Drug: Dexamethasone

Drug: Rovalpituzumab tesirine

Topotecan

Active Comparator group

Description:

Topotecan given as an intravenous (IV) infusion over 30 minutes at a dose of 1.5 mg/m\^2 on Days 1 to 5 of each 21-day cycle.

Treatment:

Drug: Topotecan