A Study of Ramucirumab (LY3009806) in Combination With Erlotinib in Previously Untreated Participants With EGFR Mutation-Positive Metastatic NSCLC (RELAY)

Lilly

Status and phase: Active, not recruiting; Phase 3

Conditions: Metastatic Non-Small Cell Lung Cancer

Treatments: Drug: Erlotinib; Drug: Placebo; Drug: Ramucirumab; Drug: Osimertinib; Drug: Gefitinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT02411448

15540

2014-004824-22 (EudraCT Number)

I4T-MC-JVCY (Other Identifier)

Details and patient eligibility

About

The main purpose of this study is to evaluate the efficacy and safety of ramucirumab in combination with erlotinib as compared to placebo in combination with erlotinib in previously untreated participants with stage IV non-small cell lung cancer (NSCLC) harboring an activating epidermal growth factor receptor (EGFR) mutation (Exon 19-Del and Exon 21 L858R). Safety and tolerability of ramucirumab in combination with erlotinib will be assessed in Part A before proceeding to Part B.

The purpose of Part C is to determine the efficacy and safety of ramucirumab in combination with gefitinib in previously untreated East Asian participants with EGFR mutation-positive metastatic NSCLC and of ramucirumab in combination with osimertinib in those participants whose disease progressed on ramucirumab and gefitinib and that have T790M - positive metastatic NSCLC.

Enrollment: 545 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Cytologically or histologically confirmed diagnosis of Stage IV NSCLC as defined by the American Joint Committee on Cancer Staging Criteria for Lung Cancer (AJCC 7th edition 2009).
• Eligible for first-line treatment with erlotinib based on documented evidence of tumor harboring an activating EGFR mutation [exon 19 deletion or exon 21 (L858R) substitution mutation].
• Mandatory provision of adequate archived stage IV NSCLC tissue samples or tissue samples other than stage IV NSCLC may be acceptable (optional for part C).
• At least one measurable lesion.
• Life expectancy of at least 3 months.

Exclusion criteria

• Known T790M EGFR mutation (not applicable for Part C Period 2).
• Known leptomeningeal carcinomatosis, uncontrolled/unstable spinal cord compression, or brain metastases.
• Serious illness or medical condition.
• Ongoing treatment with CYP3A4 inducers or strong inhibitors.
• Ongoing therapy with nonsteroidal anti-inflammatory drugs for more than 2 months.
• History of gross hemoptysis.
• Significant bleeding disorders.
• Radiologically documented evidence of major blood vessel invasion or encasement by cancer.
• Radiographic evidence of intratumor cavitation.
• History of gastrointestinal perforation within last 6 months.
• History of bowel obstruction, inflammatory enteropathy or extensive intestinal resection.
• History of any arterial thrombotic event within 6 months prior to enrollment.
• The participant has any known significant ophthalmologic abnormalities of the surface of the eye.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

545 participants in 3 patient groups, including a placebo group

Ramucirumab + Erlotinib

Experimental group

Description:

Part A: 10 milligrams per kilogram (mg/kg) ramucirumab administered every 2 weeks intravenously (IV) in combination with 150 mg erlotinib daily orally. Participants may continue to receive treatment until discontinuation criteria are met. Part B: 10 mg/kg ramucirumab administered every 2 weeks IV in combination with 150 mg erlotinib daily orally. Participants may continue to receive treatment until discontinuation criteria are met.

Treatment:

Drug: Ramucirumab

Drug: Erlotinib

Placebo + Erlotinib

Placebo Comparator group

Description:

Part B: Placebo administered every 2 weeks IV in combination with 150 mg erlotinib daily orally. Participants may continue to receive treatment until discontinuation criteria are met.

Treatment:

Drug: Placebo

Drug: Erlotinib

Ramucirumab + Gefitinib or Osimertinib

Experimental group

Description:

Part C: 10 mg/kg ramucirumab administered every 2 weeks intravenously (IV) + 250 mg Gefitinib or 80 mg Osimertinib daily orally. * Ramucirumab and gefitinib administered during period 1. * Ramucirumab and osimertinib administered during period 2.

Treatment:

Drug: Osimertinib

Drug: Gefitinib

Drug: Ramucirumab