So here's what happened with Merck & Co. Inc. (MRK) on Tuesday: the stock took a hit after the company and its partner Eisai shared some not-so-great news from a big cancer trial. They were testing combination therapies for advanced clear cell renal cell carcinoma—that's the most common type of kidney cancer, by the way, making up about 75–80% of cases—and the results just didn't pan out as hoped.
The Phase 3 LITESPARK-012 trial looked at two different drug combos. One was a triplet therapy involving Keytruda (pembrolizumab), Lenvima (lenvatinib), and Welireg (belzutifan). The other was MK-1308A, which is a coformulation of Keytruda and quavonlimab plus Lenvima. Both of these were stacked up against the current standard, which is Keytruda plus Lenvima alone.
At a pre-specified interim analysis, neither of the combination regimens managed to hit the trial's dual primary endpoints: progression-free survival (how long patients live without the cancer getting worse) and overall survival (how long patients live, period). It's a miss, plain and simple.
Now, it's not all doom and gloom on the safety front. The safety profiles for these combos were in line with what's been seen in earlier studies, so at least there weren't any nasty surprises there. Merck and Eisai say they're still digging into the full dataset and will work with investigators to share the results. Importantly, this flop in the LITESPARK-012 trial doesn't throw a wrench into the other ongoing trials from the LITESPARK clinical program, including the ones they're running with Eisai.
Speaking of other trials, there's still some action on the regulatory front. As previously announced, the FDA has accepted two supplemental New Drug Applications for review based on the Phase 3 LITESPARK-011 trial, which is evaluating Welireg in combination with Lenvima for certain previously treated patients with advanced RCC. They've set a target action date of October 4.
So where does this leave Merck? Well, analysts are already thinking about plan B. William Blair put out an investor note on Tuesday suggesting that this setback with the Keytruda-Lenvima-Welireg combo might—theoretically—open a door for a different triplet regimen. They're talking about one based on zanzalintinib, a HIF-2 alpha inhibitor, especially if the efficacy numbers from the failed trial were close to being statistically significant.
Merck is already on that track with the Phase 3 LITESPARK-033 study, which is looking at zanzalintinib plus Welireg in frontline RCC patients who had previously been treated with Keytruda in the adjuvant setting. For the curious, zanzalintinib (also known as XL092) is an investigational, oral, multi-targeted tyrosine kinase inhibitor that's being developed by Exelixis Inc. (EXEL).
In other, completely unrelated news from Tuesday, the FDA did give Merck something to smile about: they approved Idvynso (doravirine and islatravir) for treating HIV-1 infection in adults. It's meant to replace the current antiretroviral regimen for folks who are virologically suppressed on a stable regimen, with no history of treatment failure and no known resistance substitutions to doravirine. So, one win amid the clinical trial stumble.
Back to the market reaction: Merck shares were down 4.08% at $112.34 at the time of publication on Tuesday. When a big Phase 3 trial misses its primary endpoints, investors tend to vote with their feet—or their sell buttons.
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