Lung Cancer's Three-Horse Race Just Got a Lot More Interesting
AACR 2026 delivered three standout lung cancer datasets: Merck's new two-in-one antibody, a rescue drug for patients who've exhausted all options, and a pill keeping cancer at bay for over four years. The NSCLC landscape just got a whole lot more competitive.
Four Years on a Single Drug. Let That Sink In.
Imagine taking a pill every day for four years, and the cancer that was supposed to kill you just… doesn't come back. That's essentially what Nuvation Bio reported at AACR 2026 for its ROS1 inhibitor taletrectinib (brand name Ibtrozi). In patients who had never taken a targeted therapy before, the median duration of response hit 49.7 months. That's more than four years of disease control from a single oral drug.
But Ibtrozi wasn't the only lung cancer story turning heads at this year's meeting. Merck debuted first-in-human data for a new type of combo-in-a-bottle cancer drug, and Nuvalent showed its experimental pill can rescue patients who've already burned through every approved option. Together, these three datasets paint a picture of a lung cancer treatment landscape that's getting smarter, more durable, and fiercely competitive.
Merck's $588 Million Bet Gets Its First Report Card
Back in November 2024, Merck paid $588 million upfront (with up to $2.7 billion in milestones) for a drug called MK-2010 from a Chinese biotech named LaNova Medicines. The reason? Merck needed an answer to a growing competitive threat.
MK-2010 is a bispecific antibody, which is basically a molecule designed to grab two different targets at once. One arm blocks PD-1 (the immune checkpoint that Keytruda already targets), while the other neutralizes VEGF (a protein that helps tumors build their own blood supply). Think of it like patching two holes in a dam simultaneously instead of fixing one at a time.
The logic is compelling: abnormal tumor blood vessels don't just feed cancer cells; they also create an environment that keeps immune cells from doing their job. Block VEGF to normalize the blood vessels, block PD-1 to unleash the immune system, and you get a one-two punch from a single infusion.
At AACR 2026, Merck showed the first-in-human results from 112 patients across a dose-escalation and NSCLC expansion study. In treatment-naïve lung cancer patients, the 20 mg/kg dose produced an unconfirmed response rate of 55%. The word "unconfirmed" matters here; these responses haven't been verified with follow-up scans yet. But for a Phase 1/2, that's a strong opening number.
Get tomorrow's biotech intelligence before your competitors.
Join thousands of biotech professionals who start their day with our free, daily briefing.
Safety looked manageable too. At the 20 mg/kg dose, only 17% of patients experienced serious side effects (grade 3 or higher), and there were no treatment-related deaths. Merck noted that the lower dose performed better on both efficacy and tolerability than the higher 30 mg/kg dose, which is a useful signal for designing the next trial.
The big question: how does this compare to ivonescimab, the rival PD-1/VEGF bispecific from Akeso that already beat Keytruda head-to-head in a pivotal NSCLC trial? Merck isn't saying much about Phase 3 plans yet. But spending nearly $600 million on a drug and then going quiet about next steps? That's either careful strategy or nervous deliberation. Either way, the PD-1/VEGF bispecific class is shaping up to be one of the most important battlegrounds in oncology.
Nuvalent's Rescue Mission for the Hardest-to-Treat Patients
Now let's shift to a much smaller corner of lung cancer: ROS1-positive NSCLC, which accounts for only 1-2% of cases. It's a rare mutation, but patients who have it face a brutal problem. After cycling through multiple targeted therapies, they eventually run out of options.
Nuvalent's zidesamtinib is designed specifically for this moment. It's a ROS1 inhibitor built to work after patients have already failed the newer drugs like repotrectinib (Augtyro) and taletrectinib (Ibtrozi). Think of it as the closer who comes in after the starter and middle reliever have both left the game.
The AACR 2026 update from the ARROS-1 trial focused on exactly this population. In 46 patients who had already been treated with repotrectinib, zidesamtinib produced a 41% response rate with a median duration of response of 15.7 months. In 19 patients previously on taletrectinib, the response rate was 47%, and the duration of response hadn't even been reached yet.
Those numbers might not sound flashy compared to first-line results. But context is everything. These are patients at the end of the line, people who've already tried multiple targeted drugs and progressed. A 41-47% response rate in that setting is clinically meaningful.
The brain data was equally striking. ROS1-positive cancers love to spread to the brain, and among patients with measurable brain lesions who had previously taken repotrectinib, the intracranial response rate was 44%. In the taletrectinib-pretreated group, it jumped to 71%, including several complete brain responses. Zidesamtinib was designed from scratch for CNS penetration while deliberately avoiding inhibition of TRK (a related target whose blockade can cause neurological side effects with other drugs). That design choice appears to be paying off.
Ibtrozi's Durability Play
While zidesamtinib carves out the late-line rescue niche, Nuvation Bio came to AACR 2026 with a different argument: what if you just pick the right drug first and patients barely need a second one?
Pooled data from the TRUST-I and TRUST-II trials in 157 treatment-naïve ROS1-positive patients showed a confirmed response rate of 89.8%. But the real headline was durability. The median duration of response clocked in at 49.7 months, the median progression-free survival was 46.1 months, and median overall survival still hasn't been reached.
To put that in perspective, the older standard crizotinib typically delivers a median PFS around 19 months. Ibtrozi is more than doubling that. For patients with brain metastases at baseline (about 23% of the cohort), the intracranial response rate was 76.5%, confirming that the drug gets into the brain effectively.
These updated numbers represent about a year of additional follow-up beyond the data that supported Ibtrozi's FDA approval in June 2025. Every extra month of follow-up that doesn't erode the survival curves strengthens the drug's case as a potential first-line standard of care.
The Chessboard Is Getting Crowded
So where does this leave the lung cancer landscape?
In the PD-1/VEGF bispecific arena, Merck's MK-2010 is early but promising, entering a race where ivonescimab already has a significant lead. The 55% unconfirmed response rate is competitive, but Merck needs to move fast. Every month without a Phase 3 announcement is a month ivonescimab extends its head start.
In ROS1-positive NSCLC, we're watching a fascinating sequencing game unfold. Ibtrozi and repotrectinib are battling for first-line supremacy, each claiming strong CNS activity and resistance-mutation coverage. Meanwhile, zidesamtinib is positioning itself as the essential safety net for when those front-line drugs eventually fail.
The real winner? Patients. A few years ago, running out of ROS1 options meant chemotherapy and hope. Now there's a credible path to four-plus years on targeted therapy up front, with a rescue drug waiting in the wings. That's not just progress; it's a fundamentally different disease trajectory.
Clinical & Regulatory
4 min read
The First Pill That Stops COVID Before It Starts
The FDA just approved the first oral antiviral that prevents COVID after exposure, not just treats it. Shionogi's Xocova cut symptomatic infection by 67% in a pivotal trial, filling a gap that's been wide open since Omicron killed off the antibody options.
