Summit Therapeutics Inc. (SMMT) saw its stock plunge approximately 23% on Friday afternoon, with shares trading at $16.60, following an interim update from the HARMONi-3 trial that failed to deliver the early positive data investors were anticipating. The biotech's high-profile lung cancer candidate, ivonescimab, did not provide the early upside the market was hoping for, triggering a sharp selloff.
In contrast, Merck & Co. (MRK), whose blockbuster drug Keytruda serves as the comparator in the trial, saw its shares rise 3% on the day. The divergence highlights the high-stakes nature of the competition between the two therapies in the first-line metastatic non-small cell lung cancer (NSCLC) setting.
Ivonescimab, known as SMT112 in Summit's licensed territories, is a bispecific antibody that targets both PD-1 and VEGF, combining two mechanisms of action in a single molecule. Summit licenses the therapy from Chinese biotech Akeso, holding rights across the Americas, Europe, Japan, and other markets outside Akeso's retained regions.
The HARMONi-3 trial is evaluating ivonescimab plus chemotherapy against Keytruda (pembrolizumab) plus chemotherapy in patients receiving first-line treatment for metastatic NSCLC. Summit reported that after an early interim analysis of progression-free survival (PFS), an independent data monitoring committee recommended the trial continue as planned, with no safety concerns flagged and the double-blind design maintained.
Progression-free survival measures how long patients live without their disease worsening. Leerink Partners analyst Daina Graybosch described the stock move as "reasonable" but highlighted "considerable uncertainty" ahead, noting a potential hazard ratio between 0.75 and 0.60, which would represent a 25% to 40% reduction in the risk of progression. Hazard ratios below 1 favor the Summit regimen.
The market's reaction was amplified by the competitive context. In China, Akeso's HARMONi-2 trial showed ivonescimab alone outperformed Keytruda by 49% in PFS among PD-L1-positive NSCLC patients. Another study, HARMONi-6, demonstrated a 40% PFS advantage for ivonescimab plus chemo over BeiGene's Tevimbra plus chemo in squamous NSCLC. These results had raised expectations for the global data.
Investors are now focusing on the upcoming overall survival (OS) readout from the China-based HARMONi-6 trial, which is set to be presented at the American Society of Clinical Oncology (ASCO) plenary session on May 31. Overall survival is a tougher benchmark and often carries more weight with both investors and regulators in late-stage cancer trials.
Meanwhile, Summit's financial results for the first quarter show rising costs. The company reported a non-GAAP net loss of $116.6 million, more than double the $51.8 million loss in the same period last year. Cash and short-term investments declined to $598.7 million from $713.4 million at year-end, reflecting the ongoing investment in clinical development.
Adding to the uncertainty, Summit's application for ivonescimab in EGFR-mutated lung cancer is under FDA review. According to Summit's 10-Q filing, the agency has indicated it expects to see a statistically significant overall survival benefit for approval in this indication, suggesting that PFS data alone may not be sufficient.
Friday's update leaves HARMONi-3 ongoing but without any unblinded data or clarity on effect size. Investors are now in a holding pattern, awaiting both the final global PFS data expected later this year and the China OS results at ASCO. For now, the stock price reflects the significant trial risk that remains.
