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Merck, Eisai’s Lenvima fails to improve on Keytruda in bladder cancer as key Padcev readout nears

Merck & Co. and Eisai’s Lenvima has posted its share of positive data readouts over the years, but bladder cancer remains a tough nut to crack.

In newly released trial results, Lenvima’s addition to Merck’s Keytruda failed to extend patients’ lives over Keytruda alone in certain patients with newly diagnosed advanced urothelial carcinoma. The patients were either ineligible to receive cisplatin chemotherapy, with their tumors expressing PD-L1 at a combined positive score of at least 10, or they couldn’t receive any platinum-based chemo regardless of PD-L1 status. Investigators released the results from the phase 3 LEAP-011 trial at the American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium.

In the trial, patients on Keytruda monotherapy lived a median of 13.8 months, besting the 11.2-month result for the combo group. Investigators saw no meaningful difference between the two regimens’ ability to prevent tumor progression.

As Scot Ebbinghaus, M.D., Merck’s therapeutic area head for late-stage oncology clinical development, sees it, the results solidify Keytruda monotherapy’s use in patients who are ineligible to receive platinum-based chemo.

Still, Keytruda isn’t exactly an ideal front-line therapy for treating bladder cancer. The PD-1 inhibitor’s current front-line bladder cancer label, restricted to platinum-ineligible patients, is smaller than the original accelerated nod it earned in 2017 for patients who aren’t suitable for cisplatin, a type of platinum chemo.

After Keytruda failed to show a survival benefit in a phase 3 confirmatory trial called KEYNOTE-361, the FDA trimmed the drug’s use to a population like those enrolled in LEAP-011. Then in August, the agency further limited its approval to patients who aren’t suitable for any platinum chemo.

Roughly one out of every five bladder cancer patients can’t take any platinum chemo, Ebbinghaus noted. Keytruda’s performance in LEAP-011 was comparable to a prior showing from the drug’s the phase 2 KEYNOTE-052 trial, which helped convert the FDA accelerated approval to the reduced full nod, he added.

Despite the latest result, Lenvima has helped Keytruda conquer cancer territories in the past. Most notably, the pairing’s data—and subsequent FDA nod in August—in previously untreated kidney cancer triggered best-in-class evaluations.

But the combo has had its fair share of setbacks, as well. The FDA in 2020 rejected an application for Keytruda and Lenvima in newly diagnosed liver cancer, criticizing immature data with only tumor response numbers from a phase 1b trial. LEAP-002, the phase 3 trial for that indication, currently has a primary completion date next July.

In one recent flop, adding Lenvima to Keytruda also failed to improve upon Keytruda monotherapy in newly diagnosed PD-L1-positive non-small cell lung cancer. The results, from the LEAP-007 trial, confirmed Keytruda monotherapy as the standard of care in that setting, the study’s investigators said.

Meanwhile, in bladder cancer, Merck is getting excited about the potential of Keytruda’s combination with Seagen and Astellas’ antibody-drug conjugate Padcev. The anti-nectin-4 drug already has its own bladder cancer approvals in previously treated disease.

The closely watched cohort K of the phase 1b/2 EV-103 trial, also known as KEYNOTE-869, recently finished enrollment of cisplatin-ineligible bladder cancer patients to receive the Keytruda-Padcev combo in the first-line setting. The readout from that group is expected in the latter half of the year and, if positive, might lead to accelerated approval for the regimen.