Eli Lilly Announced Positive Results from Phase 3 RELAY trial of CYRAMZA®

| By | Cancer Drugs, Clinical Trials, Eli Lilly

Eli Lilly and Company announced that results from the global Phase 3 RELAY trial of CYRAMZA® (ramucirumab) in previously untreated patients with metastatic EGFR-mutated non-small cell lung cancer (NSCLC) were published in The Lancet Oncology.

In the RELAY study, treatment with CYRAMZA in combination with erlotinib demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) – the time patients lived without their cancer growing or spreading after starting treatment – compared to erlotinib alone. The CYRAMZA-erlotinib combination achieved a median PFS of 19.4 months, corresponding to a seven-month improvement over erlotinib alone. There were no new safety signals and the safety profile observed in the trial was consistent with what has been previously observed for CYRAMZA in other Phase 3 clinical trials and the established safety profile of erlotinib.

“The findings from RELAY show the utility of targeting the VEGFR and EGFR pathways together in this setting, and validate previous non-clinical and clinical studies which demonstrated interactions between EGFR and VEGFR2 signaling in the setting of EGFR mutations,”

said Kazuhiko Nakagawa, M.D., Department of Medical Oncology, Kindai University Faculty of Medicine, and global lead principal investigator of the RELAY trial.

Dr. Nakagawa added,

“Although EGFR TKIs have proven effective for the first-line treatment of EGFR-mutated non-small cell lung cancer, most patients will experience disease progression and prognosis remains poor. These results suggest the combination of CYRAMZA plus erlotinib has the potential to be an important first-line treatment option for people with metastatic EGFR-mutated non-small cell lung cancer.”

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. Tyrosine kinase inhibitors (TKIs) – including erlotinib, which was used in the trial – are the current standard treatment option for EGFR-mutated NSCLC.

“Despite recent treatment advances in metastatic EGFR-mutated NSCLC, there is an ongoing unmet need for additional first-line treatment options and new treatment strategies,”

said Edward Garon, M.D., David Geffen School of Medicine, University of California, and North America lead investigator of the RELAY trial.

“Therapeutic combinations are one such strategy to provide more options for patients that can potentially delay disease progression and the emergence of acquired resistance.”

On the primary endpoint of investigator-assessed PFS, CYRAMZA plus erlotinib (N=224) demonstrated a statistically significant and clinically meaningful improvement in median PFS 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=<0.0001)]. Improvements with CYRAMZA plus erlotinib were also 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 patients with tumors that had exon 19 and 21 mutations. Historically, patients receiving single-agent EGFR-TKIs with exon 21 (L858R) point mutations typically have had lower PFS benefit than those with exon 19 mutations. Overall survival (OS) was immature at the time of analysis. No detriment to OS was observed at this interim assessment, and the trial will continue until it reaches its final number of OS events.

Targetable mutations play a key role in identifying treatment options in NSCLC. The most common mechanism of acquired resistance to first-line treatment with first- and second-generation EGFR-TKIs is the T790M mutation, with approximately 30 to 60 percent of patients whose disease progresses acquiring the mutation. In RELAY, the rate of T790M mutations following disease progression was similar between treatment groups.

The most common Grade ≥3 adverse events occurring at a rate of five percent or greater in the CYRAMZA-containing arm were hypertension (N=52 [24%, Grade 3 only]), dermatitis acneiform (an acne-like rash) (N=33 [15%, Grade 3 only)], and diarrhea (N=16 [7%, Grade 3 only]).

“The RELAY data are the strongest clinical evidence to date for targeting both the EGFR and VEGFR pathways to treat this type of cancer. We’re excited by these results and the promise they may hold for metastatic non-small cell lung cancer patients with an EGFR mutation,”

said Maura Dickler, M.D., vice president of late phase development, Lilly Oncology.

“The RELAY trial is another example of Lilly’s deep commitment to providing new treatment options to people with lung cancer, and the value that CYRAMZA can provide in advanced or metastatic cancers.”

Results from this study are the basis for global regulatory submissions. Lilly has made submissions in the U.S. and the EU, and a submission in Japan is planned by year-end.

RELAY is the second positive Phase 3 study of CYRAMZA in metastatic non-small cell lung cancer. In the positive Phase 3 REVEL study, CYRAMZA plus docetaxel was compared to placebo plus docetaxel in people with metastatic NSCLC whose cancer had progressed on or after prior platinum-based chemotherapy for locally advanced or metastatic disease. The primary endpoint of OS was met, as well as key secondary endpoints of PFS and response rate. The REVEL results supported CYRAMZA’s current indication in second-line metastatic NSCLC.