Full Phase 3 results in biliary tract cancer showed a median survival gain of 2.8 months and a 25% lower risk of death. The trial ran only in China, Summit is starting a separate U.S. study, and the stock's first FDA decision, in lung cancer, is due Nov. 14.
AstraZeneca's cancer drug Imfinzi lost a head-to-head survival trial on Sunday. Four weeks earlier, AstraZeneca paid $2 billion for a stake in the company that owns the winner's U.S. rights.
At the European Society for Medical Oncology congress, Akeso presented full results from HARMONi-GI1, a Phase 3 trial in first-line advanced biliary tract cancer. Ivonescimab plus chemotherapy extended median overall survival to 14.9 months, against 12.1 months for Imfinzi plus chemotherapy, at a planned interim analysis. The hazard ratio was 0.75, a 25% reduction in the risk of death, and the trial enrolled 682 patients with a median follow-up of 14.3 months.
The other measures pointed the same way. Progression-free survival improved with a hazard ratio of 0.61, and 53.8% of patients responded to treatment, against 32.5%. Serious treatment-emergent side effects were about equal, at 43.4% and 43.7%, and fewer patients on ivonescimab stopped treatment because of them.
Summit Therapeutics, which holds rights to the drug in North America, Europe, Japan and other territories, called it the "first known Phase III study in advanced biliary tract cancer to demonstrate overall survival superiority" over an anti-PD-(L)1 therapy combined with chemotherapy. That claim is the company's.
What is new and what isn't
The result itself was announced on Aug. 25, without figures. Summit's shares rose 4.9% and 6.5% over the two sessions that followed. What investors did not have until Sunday was the size of the win, against an active standard of care rather than a placebo.
They also now have a clear statement of its limits. The trial was "conducted in China and sponsored by Akeso, with all relevant data exclusively generated, managed, and analyzed by Akeso," Summit said. Ivonescimab is not approved anywhere in Summit's territories. Summit plans to begin its own U.S. registration-enabling Phase 2/3 study in the same cancer, comparing ivonescimab with Merck's Keytruda or Imfinzi, in the fourth quarter through a cooperative research group.
U.S. regulators have been skeptical of China-only data before. In 2022, an FDA advisory committee voted 14 to 1 that a different PD-1 drug, sintilimab, needed an additional trial applicable to American patients. That vote concerned another drug and was not binding.
The price gap
AstraZeneca agreed on Sept. 28 to invest $2 billion in convertible preferred stock equivalent to about 12% of Summit's common shares, at $18.36 a share. That price was the prior week's average plus 10%.
Summit closed Friday at $15.47, 15.7% below AstraZeneca's price, after falling 12.1% from its Oct. 9 close of $17.59. At that close, AstraZeneca's stake is worth roughly $1.69 billion on paper. In thin premarket quotes early Monday, the stock was bid at $15.48 and offered at $15.68, little changed.
Two readings
The first is that the market is underpricing breadth. A randomized, double-blind survival win against an active PD-L1 regimen, in a second tumor type and with a clean safety comparison, is the kind of evidence that should raise confidence in ivonescimab's global trials. Summit says all five Phase 3 readouts to date have been positive, and the owner of the beaten comparator is now one of its largest investors.
The second is that Sunday's data do not change Summit's U.S. timeline. The biliary indication needs the new U.S. study. The near-term binary is the FDA's Nov. 14 goal date for ivonescimab in EGFR-mutant lung cancer, which rests on Summit's global HARMONi trial. That trial's primary survival analysis produced a hazard ratio of 0.79 that did not reach statistical significance.
What to watch
Summit's first session on the data on Monday against biotech benchmarks, the FDA's action on or before Nov. 14, the start of the U.S. biliary study, and longer survival follow-up from HARMONi-GI1.