The FINANCIAL -- Eli Lilly and Company on April 4 announced top-line results from its Phase 3 REACH-2 study of CYRAMZA (ramucirumab) as a single agent in the second-line treatment of people with hepatocellular carcinoma (HCC), also known as liver cancer.
The trial met its primary endpoint of overall survival (OS) as well as the secondary endpoint of progression-free survival (PFS). CYRAMZA has now demonstrated a survival benefit in four aggressive, difficult-to-treat tumor types in Phase 3 studies, including as a single agent in both gastric cancer and HCC.
The safety profile observed in the REACH-2 study was consistent with what has been previously observed for single-agent CYRAMZA. The only Grade ≥3 adverse events occurring at a rate of five percent or greater in the CYRAMZA arm were hypertension and hyponatremia (low sodium). The efficacy and safety results will be submitted for presentation at a future medical meeting, according to Eli Lilly.
REACH-2 is the first positive Phase 3 HCC trial in a biomarker-selected patient population. The REACH-2 study evaluated the benefit of CYRAMZA treatment in HCC patients who were intolerant to, or had disease progression while on or following treatment with, sorafenib and had a high alpha-fetoprotein (AFP-High), defined as an AFP of ≥400 ng/mL. Approximately half of all advanced HCC patients are AFP-High and these patients are among those with the poorest prognosis relative to the general HCC patient population. While there have been some recent advances in treating HCC, there remains a very high unmet need for patients in this treatment setting.
"Advanced liver cancer is an aggressive disease that has a poor prognosis – and for those that have elevated AFP levels, the prognosis is even more dismal. The expected survival of these patients is only a few months following first-line treatment if they don't go onto second-line therapy. For this reason, Lilly is encouraged by the results of REACH-2 and the potential for CYRAMZA to benefit patients in this setting," said Levi Garraway, M.D., Ph.D., senior vice president, global development and medical affairs, Lilly Oncology.
With this positive outcome, the REACH-2 study has confirmed the hypothesis generated by the REACH trial results,1 which showed that a pre-specified subgroup of advanced HCC patients who were AFP-High derived a survival benefit from treatment with CYRAMZA following first-line treatment with sorafenib. This REACH-2 outcome also builds upon Lilly's efforts and commitment to providing treatment options for people living with HCC and gastrointestinal cancers. In addition to the Phase 3 REACH and REACH-2 trials, Lilly is evaluating CYRAMZA with an immuno-oncology agent in HCC in a Phase 1b study cohort, and is conducting various studies of CYRAMZA in other gastrointestinal cancers, including gastric, colorectal and biliary tract.
Dr. Garraway added, "We thank the patients, their caregivers and investigators for their support of and participation in the REACH-2 study. Without their contributions, we could not have achieved today's milestone – which represents important progress in our efforts to help people living with liver cancer and, more broadly, gastrointestinal cancers."
Lilly intends to initiate regulatory submissions in mid-2018.
Previously completed Phase 3 studies of CYRAMZA have demonstrated benefit in advanced forms of gastric, non-small cell lung and colorectal cancer – three of the world's leading causes of cancer-related death. An ongoing Phase 3 trial in advanced urothelial carcinoma has met its primary endpoint of PFS, and OS data are expected in the first half of 2018. Another ongoing Phase 3 study of CYRAMZA – in EGFR-positive non-small cell lung cancer – is ongoing, with an expected PFS data readout in late 2018.