Merck's Secret Weapon for Life After Keytruda

In treatment-naïve patients whose tumors expressed PD-L1 (a marker that predicts response to checkpoint therapy), the results were encouraging. At the 20 mg/kg dose, the unconfirmed overall response rate (ORR) hit 55%. That means more than half the patients saw their tumors shrink meaningfully. The 30 mg/kg dose came in at 44%.

For context, those numbers are in the same ballpark as the current frontrunner in this space: ivonescimab, the PD-1/VEGF bispecific from Akeso and Summit Therapeutics, which posted a 50% ORR in its Harmoni-2 trial. Merck isn't leading the pack, but it's running with it.

Previously treated patients (the tougher crowd) saw more modest responses: 18% at 20 mg/kg and 22% at 30 mg/kg. That's expected. Second-line patients have already seen checkpoint therapy fail, so moving the needle at all is notable.

The Safety Trade-Off

This is where things get interesting, and where the dose selection story matters. The 20 mg/kg group had a much cleaner safety profile: only 23% of patients experienced serious side effects (grade 3 or higher). At 30 mg/kg, that number jumped to 49%.

The most common VEGF-related issues were proteinuria (protein in the urine, seen in 17-24% of patients) and hypertension (19-23%, with fewer than 10% reaching grade 3). There were also bleeding events in 16% of the higher-dose group. Five deaths occurred across all cohorts, including hemoptysis and pneumonia, but investigators assessed them as unrelated to the drug.

The takeaway: the 20 mg/kg dose looks like the sweet spot. It delivered the highest response rate with the most manageable side effects. Merck described the data as showing "early signs of promising anti-tumor activity" and flagged the lower dose as the one to watch for future monotherapy or combination studies.

A Crowded Race with No Clear Winner

Merck isn't the only pharma giant betting on PD-1/VEGF bispecifics. This class has become one of the hottest areas in oncology, and the competition reads like a who's-who of Big Pharma.

Akeso/Summit's ivonescimab is the clinical leader, already in pivotal trials. Pfizer has PF-08634404 in phase 3, directly challenging Keytruda in NSCLC. BioNTech and BMS are pushing pumitamig forward. It's a stacked lineup, and Merck is arguably the latecomer.

That's partly by design. Merck licensed MK-2010 from LaNova Medicines in 2024 for $588 million upfront, a deal that signaled just how seriously the company takes the post-Keytruda era. But the company hasn't announced any phase 3 plans yet, which puts it behind competitors who are already running registration-quality trials.

The Bigger Picture: Merck's Post-Keytruda Playbook

MK-2010 is just one piece of a broader survival strategy. Merck has been assembling an oncology arsenal through aggressive deal-making: the Harpoon Therapeutics acquisition brought in T-cell engagers in mid-stage trials for lung cancer, and a $700 million deal with Curon Biopharmaceutical brought in a bispecific targeting blood cancers.

On the defensive side, Merck launched Keytruda Qlex, a subcutaneous (under-the-skin) formulation approved by the FDA in September 2025. Priced at parity with IV Keytruda (around $12,000 per three-week course), it's designed to retain patients who might otherwise switch to biosimilars by offering a more convenient injection format.

The strategy is essentially a two-pronged approach: extend Keytruda's life as long as possible while building a diverse portfolio of next-generation therapies that can pick up the slack.

So, Will It Work?

The honest answer: it's too early to tell. MK-2010's data comes from just 72 patients in the backfill cohorts, with a median follow-up of only 3.3 months. The response rates are unconfirmed, meaning they haven't been verified on follow-up scans. And Merck's silence on phase 3 plans is conspicuous when rivals are already sprinting toward regulatory filings.

But the 55% response rate at the lower, better-tolerated dose is a legitimate signal. If those numbers hold up with longer follow-up and in larger trials, MK-2010 could become a meaningful revenue contributor in the post-Keytruda world.

Merck has built its entire modern identity around one drug. Now it needs to prove it can build the next chapter. The clock is ticking, and AACR 2026 was the first real glimpse of what comes after the empire's crown jewel loses its shine.

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