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.
“These study results add to our understanding of this combination and will inform our future research as we strive to improve outcomes for more patients with cancer,” Gregory Lubiniecki, VP of global clinical development at Merck Research Laboratories, said in a statement.
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).
For sac-TMT, Merck has launched 10 global phase 3 trials in multiple disease settings, even though it only has China phase 3 data from Kelun in triple-negative breast cancer and EGFR-mutant NSCLC.
“We think that we’re going to see really good data with sac-TMT beyond the data that’s seen in the Kelun studies, and some of the studies actually have been run outside of China only, some of the phase 1 and phase 2 studies,” Marjorie Green, Merck’s head of oncology clinical development said during an investor event in June. “So we have some data where we’re seeing really good efficacy not only in the China’s population but also in other regions.”
Similarly, after a positive phase 2 melanoma trial and before reading out from a phase 3 melanoma study, Merck and Moderna have pushed mRNA-4157 into two pivotal studies in early-stage NSCLC.
“It will be important to see what other ways we can use V940,” Merck’s chief medical officer Eliav Barr said during the same investor event. “I think they were right at the beginning of a very long exploration as we improve on this modality.”