Summit Therapeutics today provided updated overall survival data from its phase 3 HARMONi study using its PD-1/VEGF bispecific antibody inhibitor ivonescimab [SMT112] for the treatment of patients with EGFR mutant [EGFRm] locally advanced or metastatic non-squamous non-small cell lung cancer [NSCLC]. These were 2nd-line patients because they had already been previously treated with a third-generation EGFR tyrosine kinase inhibitor [TKI].

The reason for this update stems from a problem that started back in April of 2025, when the company performed a primary overall survival [OS] analysis. With respect to this being done, it was noted that ivonescimab in combination with chemotherapy showed a positive trend on this endpoint but did not reach statistical significance [p-value of p=0.057]. The point is that at that time, it was shown that this ivonescimab combination reduced the risk of death by 21% [HR 0.79].

The company attributed this to happening because there was only a 9.2-month follow-up period for Western patients. The next update in September of 2025 then led to an HR of 0.78 [22% reduction in the risk of death]. The point here is that with Summit reaching this latest analysis, with a cutoff date of June 2026, this OS number improved even more with an HR of 0.76. That’s not all; there was a premise of noting that the Western patients also had a follow-up of 23.2 months. Thus, this subpopulation of only Western patients also achieved an HR of 0.76.

Having said all of that, this newly updated OS data from the phase 3 HARMONi study is important. That’s because it was submitted to the FDA. The reason for doing so is that there is a pending FDA decision on ivonescimab in combination with chemotherapy to treat these 2nd-line EGFRm NSCLC post-TKI therapy patients. Specifically, the FDA accepted the Biologics License Application [BLA] filing of this ivonescimab for the treatment of these patients and set a Prescription Drug User Fee Act [PDUFA] target action date of November 14, 2026.

The downside is that this newly submitted data might constitute a major amendment. Thus, while not guaranteed, it is possible that the PDUFA date could end up being extended to allow additional time for the FDA to review the application. Ivonescimab is definitely a strong drug. That’s because such an OS benefit that is now being shown in the phase 3 HARMONi study has already been shown in another late-stage trial.

This would be the phase 3 HARMONi-6 study, which is being conducted by Summit’s partner Akeso. This particular trial is evaluating the use of ivonescimab in combination with platinum-based chemotherapy to treat patients with locally advanced or metastatic squamous NSCLC irrespective of PD-L1 expression status.

The point here is that this particular study is pitting up this ivonescimab combination to what is normally used for these patients, which is a PD-1 inhibitor in combination with chemotherapy. In this case, the comparator arm is the PD-1 inhibitor tislelizumab in combination with chemotherapy. The ivonescimab combination performed very well, being able to reduce the risk of death by 34% [HR of 0.66].

Plus, this study already met the primary endpoint of progression-free survival back in April of 2025. The main point here is that this PD-1/VEGF bispecific inhibitor can be used to treat a lot of other solid tumor types. There are a total of 15 phase 3 studies across the entire pipeline program, 4 of which are sponsored specifically by Summit itself.

The PD-1 inhibition portion of the drug blocks the PD-1/PD-L1 axis, and the purpose of this is to release the brakes on dormant immune cells. The VEGF inhibition portion is then responsible for preventing blood vessel growth that feeds the tumor. With both of these actions happening at the same time, it is believed that it might be possible to achieve an improved clinical outcome for patients.