Analysts, investors and partner Summit Therapeutics had all been keenly awaiting the overall survival update, after previous data from Akeso’s HARMONi-6 trial left them wanting.
Summit Therapeutics’ Chinese partner Akeso has achieved an overall survival benefit for the VEGF/PD-1 therapy ivonescimab that experts were looking for: a four-month improvement in patients with a type of lung cancer.
One key opinion leader told Truist Securities ahead of the readout that a four-month survival benefit would be “clinically meaningful and practice changing.”
The eagerly anticipated results from the HARMONi-6 trial, being run in China by Akeso, were reported at the American Society for Clinical Oncology meeting on Sunday. The trial features 532 patients with first-line advanced squamous non-small cell lung cancer (NSCLC) who were split between the treatment and standard of care control arm.
The Phase 3 study showed that treatment with ivonescimab plus chemotherapy led to an overall survival (OS) rate of 27.9 months, compared to 23.7 months in the arm that received BeOne’s Tevimbra plus chemotherapy. There was little divergence in the OS based on PD-L1 protein expression, according to an ASCO press release.
The results were statistically significant, with a hazard ratio (HR)—a measure of the overall risk of death—of 0.66.
Prior to the readout, Leerink Partners had said the OS HR was “trending towards 0.80,” but that 0.70 to 0.72 would be even better. Akeso and Summit’s therapy more than cleared that bar.
One expert Truist spoke to said that 0.75 or lower would be “a complete game changer.” This expert doubted, however, that the number would reach 0.6 because VEGF agents typically do not reach that bar.
“This is the first large prospective trial to prove that an anti-PD-1/VEGF bispecific therapy plus chemotherapy is superior to the established standard of PD‑1 inhibitor plus chemotherapy in patients with advanced squamous lung cancer,” said David Spigel, president and chief medical officer at the Sarah Cannon Research Institute and lung cancer expert provided by ASCO.
Now for the rest of the world
Analysts, physicians and investors alike had been keenly awaiting the OS update, after previous data from the HARMONi-6 trial showed progression-free survival (PFS) of 11.4 months, as compared with 6.9 months in the comparator arm. This beat expectations but analysts at the time noted that the OS data was not yet mature enough to report.
Now they have their answer. The cancer care community had been hoping for big things from the HARMONi-6 trial, with one expert telling Leerink that they expected “a ‘magnificent’ OS HR of less than 0.5 from HARMONi-6 due to its selection for a plenary presentation over ‘so many good abstracts’ this year.”
Indeed, the Akeso abstract was one of two major readouts expected at ASCO, the other being Revolution Medicines’ pancreatic cancer data that has inspired myriad mainstream media takes of a potential major breakthrough in the intractable cancer.
The challenge for Summit and Akeso now will be to replicate these data in a non-Chinese dataset, with final PFS and interim OS results for patients with squamous NSCLC from a Phase 3 trial called HARMONi-3 due in the second half. Data from the non-squamous cohort will arrive in the first half of 2027.
An early interim analysis of PFS from HARMONI-3 disappointed analysts by not reaching statistical significance. The small update, which arrived in early May, nixed Summit’s plans for an earlier regulatory filing.
It also added pressure on the OS data for HARMONi-6, Leerink analyst Daina Graybosch recently told BioSpace. “If you believe that the data is going to degrade in effect from China to a global study, you need to see a really impressive result in China.”
HARMONi-6 enrolled about 90% male patients who smoked. Experts told Leerink that these patients may experience even more benefit from immuno-oncology agents, which means a more heterogeneous global population like in HARMONi-3 would have different results. But if successful, the HARMONi-3 data could help support an approval for an earlier line of therapy.
Summit has already submitted ivonescimab to the FDA as part of a combo chemotherapy regimen for patients with locally advanced or metastatic non-squamous NSCLC who harbor EGFR mutations. The agency is expected to make a decision on the application in November.
If the therapy is approved, Summit could unseat Merck’s immuno-oncology stalwart Keytruda in this type of second line lung cancer treatment.
