A 50.7% pathological complete response rate in a Phase II trial tends to get attention, and that is the number at the center of Akeso’s Nature Medicine publication on ivonescimab in perioperative resectable non-small cell lung cancer. Among patients who received neoadjuvant ivonescimab plus chemotherapy and proceeded to surgery, 70.1% met the major pathological response threshold, every patient who had surgery achieved R0 resection, and 12-month event-free survival exceeded 80%. Those figures matter because KEYNOTE-671, the perioperative pembrolizumab trial that now anchors standard-of-care thinking, posted a pCR rate of roughly 18% in its neoadjuvant chemotherapy-plus-pembrolizumab arm. Ivonescimab’s pCR numbers are not from a randomized head-to-head, but the gap is large enough that investigators will be watching how Phase III data land.
The subgroup results add clinical texture. Squamous histology patients, a population historically harder to treat, reached an MPR rate of 81.5% and a pCR rate of 61.1%. PD-L1-negative patients achieved a 69.2% MPR rate, essentially matching PD-L1-positive patients, which matters because PD-L1 negativity is exactly the population where existing checkpoint regimens reliably underperform. Even the monotherapy arm produced an MPR of 60.0% and a pCR of 30.0%, a signal worth noting given that perioperative programs have generally relied on chemotherapy to achieve meaningful pathological responses.
Safety held up at an operational level. No grade 3 or higher bleeding events occurred, and no surgeries were cancelled because of treatment-related toxicity. Those two facts matter practically: VEGF-targeting agents carry a known surgical bleeding concern, and surgeons evaluating neoadjuvant regimens watch closely for anything that forces cancellations or delays. A clean surgical record in a Phase II does not guarantee it at scale, but it removes an early objection.
Ivonescimab combines PD-1 and VEGF blockade in a single bispecific molecule, and Akeso has licensed rights in the United States and Canada, South America, Europe, the Middle East, Africa, and Japan to Summit Therapeutics under an agreement worth up to $5 billion. With eight Phase III lung cancer studies now running in the broader program, the perioperative indication is one piece of a large registrational effort. The number to track from here is the MPR and pCR readout from whichever perioperative Phase III completes first, because that is where the head-to-head validity question gets answered.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
