ASCO 2026: Attention might be on the Wrong Drug in Frontline Lung Cancer
Sac-TMT may be unlike other TROP2 ADCs and poses a real threat to the PD-1xVEGF class in 1L NSCLC
Frontline (1L) lung cancer always gets a ton of attention. It is arguably the single most important indication set in all of the KEYTRUDA (pembrolizumab; pembro) indications, allowing it to become one of the greatest therapeutics of all time.
1L NSCLC took center stage once again at ASCO 2026. All eyes were focused on Akeso and Summit’s SMMT 0.00%↑ HARMONi-6 data readout, studying the leading PD-1xVEGF bispecific antibody, ivonescimab (ivo), head-to-head vs. pembro in 1L NSCLC. Many caveats with this study hold, most notably that it is a China-only study. Frankly that caveat applies to a lot of the PD-(L)1 x VEGF class, as many of the leading programs being taken forward by US/EU developers originally came from China.
Summit is running a sister global study called HARMONi-3 studying ivo against pembro in squamous (~30% of NSCLC, typically older patients, worse prognosis, more smoking-driven) and non-squamous (~70% of NSCLC, typically younger patients, better prognosis but still bad, less smoking-driven) 1L NSCLC in separate cohorts.
The anticipation around HARMONi-6 is because it has read-through to HARMONi-3. That’s the case for BioNTech BNTX 0.00%↑ and Bristol-Myers’ BMY 0.00%↑ pumitamig as well, which originally came from Chinese Co Biotheus. Though BNTX actually presented global data from the P2 portion of the P2/3 Rosetta LUNG-02 study at ASCO, examining pumitamig + chemo in squamous and non-squamous 1L NSCLC.
The same thing can also be said for Sacituzumab tirumotecan (sac-TMT, TROP2 ADC) from Merck MRK 0.00%↑ and their Chinese partner, Kelun Biotech, which presented interim Phase 3 data from the OptiTROP-Lung05 study at ASCO.
While HARMONi-6 captured more attention, getting a prime viewing slot as a late-breaker, I actually though the Sac-TMT data looked more promising. Maybe its just the buzz associated with the PD-1xVEGF class and all the deal activity we’ve seen in that space, contrasted with the ups and downs the TROP2 class that has been weighing it down.
The outside world tends to look at competition largely through an in-class lens. Not always, but most of the time. PD-1s get compared to PD-1s. PD-1 x VEGFs get compared to PD-1 x VEGFs. CD19 CAR-T gets compared to CD19 CAR-T…and so and so on.
That’s a helpful angle when you’re comparing several companies and you want to get a better read or refine your thesis on whose stock will win out in that space.
Inside the walls of BioPharma, program teams take a much wider aperture. You are not only directly competing with the drugs in your class, you are also directly competing with drugs outside of your class. Doctors and patients don’t make treatment decisions in a within-class vacuum. Every possible option for your disease in your line of therapy is being considered.
So when we think about PD-1xVEGF in lung cancer, we also need to apply that broader lens, and consider out-of-class options that could steal prescriber share from them. After ASCO, its my belief that Sac-TMT is the one to watch out for for the entire PD-(L)1 x VEGF class going after NSCLC.
Let’s start by looking at a comparison of the data presented at the conference. In the gallery below I put together a side-by-side of the two China-only data sets presented by Kelun and Akeso on Sac-TMT and IVO respectively. I also threw in the P2 global data presented by BioNTech.
