Regulatory submission based on the positive Phase 3 RELAY study of CYRAMZA in combination with erlotinib for the first-line treatment of adult patients with metastatic non-small cell lung cancer with activating EGFR mutations

INDIANAPOLIS, Feb. 26, 2020 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) today announced that a U.S. Food and Drug Administration (FDA) Oncologic Drugs Advisory Committee (ODAC) voted 6-5 that CYRAMZA® (ramucirumab) plus erlotinib demonstrated a favorable benefit/risk profile for patients with untreated metastatic EGFR-positive non-small cell lung cancer (NSCLC), based on the results of the positive Phase 3 RELAY study. "Given the unmet need that remains in treating metastatic EGFR-mutated non-small cell lung cancer, we are encouraged that the majority of these experts agree CYRAMZA plus erlotinib has a favorable benefit/risk profile for the first-line treatment of these patients," said Maura Dickler, M.D., vice president of late phase development, Lilly Oncology. "We believe in the clinical meaningfulness of the data from the RELAY trial, which targeted the VEGFR and EGFR pathways together. We look forward to continuing to work with the FDA on this application to offer a new front-line treatment option for people with metastatic EGFR-mutated non-small cell lung cancer." The ODAC considered the safety and efficacy data from the Phase 3 RELAY trial, which is the basis for the CYRAMZA supplemental Biologics License Application (sBLA) currently under review by the FDA. In the RELAY study, CYRAMZA, a VEGF receptor 2 antagonist, in combination with erlotinib, a globally approved EGFR-targeting tyrosine kinase inhibitor (TKI), demonstrated a statistically significant and clinically meaningful improvement in progression-free survival – the time patients live without their disease getting worse – compared to erlotinib alone. Median PFS on the CYRAMZA-plus-erlotinib arm was 19.4 months compared to 12.4 months on the placebo-plus-erlotinib arm, an improvement of seven months (HR 0.59; 95% CI, 0.46-0.79; P5% incidence) Grade ≥3 adverse events occurring at a higher rate (≥5% difference) on the CYRAMZA-plus-erlotinib arm compared to the placebo-plus-erlotinib arm were hypertension, dermatitis acneiform (an acne-like rash), and diarrhea. There is no cure for people with metastatic EGFR-mutated lung cancer and disease progression following acquired resistance remains a challenge. Most patients receive several lines of treatment and the therapeutic regimen prescribed for first-line treatment can impact a person's options for later lines of therapy. Globally, tyrosine kinase inhibitors (TKIs) – including erlotinib, which was used in the trial – are the current standard treatment option for EGFR-mutated NSCLC. There remains an ongoing need for additional first-line therapeutic options that provide clinically meaningful benefits – including delaying disease progression and use of chemotherapy as long as possible. Moreover, new treatment options could allow oncologists greater choice on how to use the available agents, in shared decision-making with their patients. Advisory committees provide the FDA with independent opinions and recommendations from outside medical experts during the drug review process. The FDA is not obligated to follow their recommendation, but it often does. Lilly has also made regulatory submissions outside the U.S. based on the RELAY data. In January 2020, the European Commission granted European Union approval for CYRAMZA in combination with erlotinib for the first-line treatment of adult patients with metastatic NSCLC with activating EGFR mutations. Lilly has submitted in Japan and expects regulatory action in the second half of 2020.

About the RELAY TrialRELAY is a global randomized, double-blind, placebo-controlled Phase 3 study of CYRAMZA in combination with erlotinib, compared to placebo in combination with erlotinib, as a first-line treatment in previously untreated patients with metastatic NSCLC whose tumors have EGFR (epidermal growth factor receptor) exon 19 deletions or exon 21 (L858R) substitution mutations. EGFR-targeting tyrosine kinase inhibitors (TKIs) are the current standard treatment options for EGFR-mutated NSCLC. Erlotinib, the TKI included in the RELAY trial regimen, is a globally approved treatment option for this type of lung cancer.

Initiated in 2015, the study randomized 449 patients across North America, Europe and Asia. The primary endpoint of the RELAY trial is progression-free survival (PFS); key secondary endpoints include safety, response rate, overall survival (OS), and patient-reported outcomes. On the primary endpoint of investigator-assessed PFS, CYRAMZA plus erlotinib (N=224) demonstrated statistically significant and clinically meaningful improvement in median PFS – the time patients live without their cancer growing or spreading after starting treatment – by seven months compared to placebo plus erlotinib (N=225) [19.4 months with the CYRAMZA-containing arm compared to 12.4 months with the placebo-containing arm (HR 0.59; 95% CI, 0.46-0.79; P