Merck, Eisai's
Merck, Eisai's star-crossed Keytruda-Lenvima combo misses survival goal in GI cancer trial
Merck & Co. and Eisai have to deal with the reality that yet another phase 3 trial of their combination of Keytruda and Lenvima didn’t exactly go their way.
The Keytruda-Lenvima regimen, used on top of chemotherapy, didn’t significantly improve the life span of patients with newly diagnosed, advanced HER2-negative gastroesophageal adenocarcinoma, according to a final analysis of the phase 3 LEAP-015 trial unveiled Friday. The analysis compared the regimen against chemotherapy alone.
Still, the companies noted a statistically significant win for the combo on the trial’s other dual primary endpoint, progression-free survival, as well as on the secondary endpoint of objective response rate, at an interim analysis.
Merck and Eisai said they’re running a full evaluation of the data and plan to present the results at a medical meeting, without mentioning any regulatory plans. They also didn’t specify if the failed overall survival endpoint trended in favor of the combo.
Although the LEAP-015 readout is technically positive given the trial’s dual primary endpoint design, the prospect of an approval in this use remains uncertain. As Merck noted in its press release, Keytruda secured its FDA nods in advanced HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma and in esophageal or GEJ carcinoma based on overall survival data against chemo from phase 3 trials.
The LEAP-015 readout follows a string of outright failures from the LEAP family of trials for the Keytruda-Lenvima cocktail. These include LEAP-006, LEAP-007 and LEAP-008 in different non-small cell lung cancer settings, plus other studies in first-line liver cancer, mismatch repair proficient endometrial cancer, PD-L1-positive head and neck cancer and more.
In a rare win, the combo showed it could work on top of chemoembolization in intermediate-stage liver cancer.
The repeated failures have prompted some criticism of Merck’s aggressive clinical development strategy, as the company in some instances had pushed into late-stage testing without mid-stage validation.
Lately, such questions are being redirected to Merck’s other more important pipeline assets such as Kelun Biotech-partnered TROP2 antibody-drug conjugate sac-TMT and the Moderna-partnered personalized cancer vaccine mRNA-4157 (V940).
