Liver Cancer Rejection Letter Dates to 2020 as Lenvima Alliance Revenue Rises to $287 Million
Key Facts
Available information does not establish that a new regulatory decision was issued on November 9, 2026, on combining KEYTRUDA and LENVIMA to treat unresectable hepatocellular carcinoma. The matching official announcement was issued by Merck and Eisai on July 8, 2020, and concerned receipt of a complete response letter on the two applications for accelerated approval of the combination as a first-line option. The companies said the letter stated that the applications did not provide evidence of a meaningful therapeutic advantage over available treatments. The documented decision therefore concerns a historical filing from 2020, not a new announcement on the date attributed to the report. Separately, Merck’s Lenvima alliance recorded revenue of $287 million in the third quarter of 2026, according to the company’s quarterly disclosure.
The two applications for accelerated approval were based, according to Merck and Eisai, on data from the Phase 1b KEYNOTE-524/Study 116 trial. The study showed what the companies described as clinically meaningful efficacy in a single-arm design, the basis on which they submitted the regulatory applications. However, the letter said the KEYTRUDA and LENVIMA combination had not demonstrated a meaningful advantage over available treatments. The companies also said the FDA had cited the approval of another combination therapy before the application decision dates. That approval was based, according to Merck’s statement, on a randomized controlled trial that showed an overall survival benefit.
The Phase 3 LEAP-002 results later added a randomized test of the combination against LENVIMA alone in patients with unresectable liver cancer. The companies announced in 2022 that the trial had not met its two primary endpoints, overall survival and progression-free survival. In the final analysis, median overall survival was 21.2 months with KEYTRUDA and LENVIMA, compared with 19.0 months with LENVIMA alone. But the improvement did not reach statistical significance under the prespecified plan. Merck said median survival in the LENVIMA-only arm was longer than in previous trials of the monotherapy, placing the comparison between the arms in the context of that study’s results.
Merck’s current page distinguishes the indication covered by the historical application from the treatment’s existing uses. It lists LENVIMA alone among first-line treatments for unresectable hepatocellular carcinoma in the United States, and does not list KEYTRUDA with LENVIMA for this indication. The companies also said LENVIMA alone is approved for this type of cancer in more than 80 countries and territories. The combination with chemoembolization was approved in China in June 2025 to treat unresectable, nonmetastatic hepatocellular carcinoma. The companies said the LEAP-012 results do not change the combination’s currently approved indications.
In LEAP-012, the companies said KEYTRUDA and LENVIMA with chemoembolization achieved a statistically and clinically significant improvement in progression-free survival compared with chemoembolization alone, and that this endpoint remained consistent with additional follow-up. The study included 480 patients, randomly assigned in a 1:1 ratio between the combination with chemoembolization and placebo with the same procedure. This study differs from the first-line application addressed by the 2020 letter, and also from LEAP-002, which compared the combination with LENVIMA alone. In the United States, Merck and Eisai said the two drugs in combination are approved for advanced endometrial cancer and certain cases of advanced kidney cancer. Another approval in 2026 provides separate context for the collaboration: on September 24, the FDA approved WELIREG with LENVIMA for certain adult patients with advanced clear cell renal cell carcinoma following treatment with a PD-1 or PD-L1 inhibitor.
In the market, Merck shares, listed under the symbol MRK, closed at $146.73 on November 6, 2026. Eisai shares, listed in Tokyo under the symbol 4523.T, closed at ¥4,858 the same day. The closing dates are three days before the story date and do not, on their own, provide evidence of a market response to the news attributed to November 9. In its third-quarter 2026 disclosure, Merck reported Lenvima alliance revenue of $287 million, compared with $258 million in the third quarter of 2025. These figures show the commercial alliance’s performance in the corresponding quarters, while the complete response letter concerning liver cancer remains a documented decision from 2020.