MSD, Eisai abandon combination trial in liver cancer

MSD and Eisai's combination of Keytruda and Lenvima has become a driver of growth for both products, but their efforts to extend the regimen into liver cancer have hit a hurdle.

The two partners said that dual therapy with PD-1 inhibitor Keytruda (pembrolizumab) and tyrosine kinase inhibitor Lenvima (lenvatinib) in patients with hepatocellular carcinoma (HCC) – the most common form of liver cancer – was unable to achieve an increase in overall survival (OS) compared to placebo in the LEAP-012 study.

The study, which compared the regimen to placebo given on top of transarterial chemoembolisation (TACE), a standard therapy for unresectable, non-metastatic HCC, was previously reported to have shown an improvement in progression-free survival (PFS), raising the hope that Keytruda/Lenvima could become an option for HCC.

"Although the progression-free survival results from this study are encouraging, unfortunately, the addition of Keytruda plus Lenvima to TACE did not show the overall survival benefit we hoped," said MSD's global clinical head, Dr Gregory Lubiniecki.

Lenvima monotherapy is already approved by the FDA as a first-line therapy for unresectable HCC, while Keytruda is a second-line option for patients previously treated with sorafenib, another TKI.

While the termination of the trial draws a line under efforts to develop Keytruda/Lenvima for unresectable, non-metastatic HCC in Western markets, the regimen has been approved for this indication in China based on the LEAP-012 PFS data.

MSD, known as Merck & Co in the US and Canada, licensed rights to Lenvima in 2018 in a near-$6 billion deal aimed at developing it as a partner drug to Keytruda. The combination has been approved for kidney and endometrial cancers, but studies in other indications, including lung, oesophageal, colorectal, and skin cancers, have disappointed.

"For years, TACE has been a standard of care for these patients, yet many experience disease progression within 12 months," said Dr Corina Dutcus, oncology global clinical development lead at Eisai. "With LEAP-012, we sought to make a meaningful difference for this patient population."

Welireg win

Earlier this week, MSD had better news from two trials of its HIF-2α inhibitor Welireg (belzutifan), LITESPARK-011 and LITESPARK-022, in earlier lines of therapy for renal cell carcinoma, a common form of kidney cancer.

LITESPARK-011 showed that Welireg and Lenvima improved PFS compared to Exelixis' Cabometyx (cabozantinib) in RCC patients who had progressed after first-line PD-1/PD-L1 inhibitor therapy, while in LITESPARK-022 Welireg plus Keytruda extended PFS when compared to Keytruda plus placebo in the first-line setting.

Welireg is already approved as a second-line monotherapy for RCC and for two rare diseases that cause tumours, and has been tipped by some analysts as a future $1.5 billion-plus blockbuster if it can move earlier in treatment. Sales were just over $500 million last year.