FDA ODAC Votes on Safety and Efficacy of Ramucirumab Plus Erlotinib for EGFR+ NSCLC

The FDA Oncologic Drugs Advisory Committee voted 6 to 5 that ramucirumab plus erlotinib demonstrated a favorable benefit and risk profile for patients with untreated metastatic EGFR-positive non-small cell lung cancer.

The FDA Oncologic Drugs Advisory Committee (ODAC) voted 6 to 5 that ramucirumab (Cyramza) plus erlotinib (Tarceva) demonstrated a favorable benefit and risk profile for patients with untreated metastatic EGFR-positive non-small cell lung cancer (NSCLC), according to Eli Lilly and Company, ramucirumab’s developer.

The committee was considering safety and efficacy data from the positive phase III RELAY study, which will be the basis for the ramucirumab supplemental Biologics License Application (sBLA) currently under review by the FDA.

“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,” Maura Dickler, MD, vice president of late phase development at Lilly Oncology, said in a press release. “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.”

In the global randomized RELAY study, researchers are evaluating ramucirumab 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 exon 19 deletions or exon 21 substitution mutations. Overall, 449 patients across North America, Europe, and Asia were randomized to the 2 arms. The primary endpoint of the trial is progression-free survival, with key secondary endpoints of safety, response rate, overall survival (OS), and patient-reported outcomes.

Ramucirumab in combination with erlotinib (n = 224) demonstrated a statistically significant and clinically meaningful improvement in PFS compared to placebo plus erlotinib (n = 225). Median PFS on the ramucirumab combination arm was 19.4 months compared to 12.4 months on the placebo plus erlotinib arm (HR 0.59; 95% CI, 0.46-0.79; P < 0.0001).

Moreover, improvements with ramucirumab plus erlotinib were consistently observed across secondary and exploratory endpoints including duration of response, PFS2, and time on targeted therapy. Improvements were also consistently seen across all specified subgroups, including the participants with tumors that exon 19 and 21 mutations. However, OS was immature at the time of analysis and the trial will continue until it reaches its final number of OS events.

Notably, the safety profile observed in the study was consistent with previous observations for ramucirumab in phase III clinical trials and the established safety profile of erlotinib. The most common (>5% incidence) grade ≥3 adverse events that occurred at a higher rate (≥5% difference) on the ramucirumab plus erlotinib arm compared to the placebo plus erlotinib arm were hypertension (n = 52 [24%, grade 3 only]), dermatitis acneiform (n = 33 [15%, grade 3 only]), and diarrhea (n = 16 [7%, grade 3 only]).

Currently, ramucirumab has 5 FDA approvals to treat 4 different cancer types. The antiangiogenic therapy is being investigated in a broad global development program that has already enrolled more than 15,000 patients across more than 100 trials worldwide, including several studies evaluating the therapy in combination with other anti-cancer therapies for the treatment of multiple tumor types.

In January 2020, the European Commission granted European Union approval for ramucirumab in combination with erlotinib for the first-line treatment of adult patients with metastatic NSCLC with activating EGFR mutations. Lilly has also submitted in Japan and anticipates regulatory action in the second half of 2020.


FDA Advisory Committee Votes in Favor of Lilly’s CYRAMZA® (ramucirumab) as First-Line Treatment for Metastatic EGFR-Mutated Non-Small Cell Lung Cancer [news release]. Indianapolis. Published February 26, 2020. investor.lilly.com/news-releases/news-release-details/fda-advisory-committee-votes-favor-lillys-cyramzar-ramucirumab. Accessed February 27, 2020.