Summit shares descend as PD-1/VEGF asset misses early survival mark

 

Summit Therapeutics planned an early interim progression-free survival readout for HARMONi-3 in the hope of enabling earlier regulatory engagement—but the early analysis delivered disappointment for the company and shareholders.

Summit made a bold bet earlier this year that the China-developed anti-PD-1/VEGF bispecific antibody ivonescimab could head to regulators early based on interim survival data. That readout arrived last week, showing that the heavily anticipated cancer asset did not meet the mark.

Summit’s shares crashed in the aftermath of the announcement, closing Friday’s trading session nearly 26% down to $16.12 per share.

An independent data board reviewed progression-free survival (PFS) data from Summit’s ongoing Phase 3 HARMONi-3 trial in squamous non-small cell lung cancer (NSCLC) and “recommended that the study continue as planned,” Summit announced in a Thursday news release.

While this update sounds innocuous enough, it indicates that the efficacy of ivonescimab, the anti-PD-1/VEGF bispecific antibody being tested in HARMONi-3, failed to meet a statistical bar that would have enabled an earlier regulatory filing.

“The purpose of this interim analysis was to provide a potential opportunity to speak with the regulatory authorities” ahead of a planned engagement later this year, when more complete PFS data would be available, Summit said. The biotech conceded that for this earlier data assessment, ivonescimab needed to clear “a meaningfully higher bar” than it would have for a later analysis.

Summit remains on-track for a pre-planned final PFS readout in the second half of this year.

A lot is riding on HARMONi-3. The study is testing ivonescimab plus chemotherapy as a first-line regimen in patients with NSCLC, with separate cohorts for squamous and non-squamous tumors. What sets HARMONi-3 apart is its use of Merck’s mega-blockbuster Keytruda as a control, potentially positioning the bispecific antibody as the new cornerstone cancer therapy depending on how the data read out.

“Market optimism is building that a statistically significant PFS result could lead to accelerated FDA approval and begin to erode Merck’s dominance in first-line lung cancer,” analysts at RBC Capital Markets wrote in an April 17 note, referring to ivonescimab’s interim PFS analysis.

Ivonescimab was originally developed by Chinese biotech Akeso. The asset works by targeting both the PD-1 and VEGF pathways—deactivating the cancer cells’ immune evasion and preventing the formation of blood vessels that would otherwise keep the tumor supplied with oxygen and other nutrients.

The drug captured the industry’s attention in September 2024 when it outperformed Keytruda in a late-stage NSCLC study, eliciting significantly better PFS in the late-stage HARMONi-2 study, which was held in China. Additional data from the late-stage HARMONi-6 study, likewise conducted entirely in China, showed significant PFS superiority over BeOne’s Tevimbra, according to an October 2025 readout.

However, concerns began to arise about the future of ivonescimab after a missed overall survival goal in a global Phase 3 trial in May 2025, sparking questions over how effective it is in Western populations.

https://www.biospace.com/drug-development/summit-shares-descend-as-pd-1-vegf-asset-misses-early-survival-mark