For the first time, Akeso and Summit Therapeutics’ closely watched PD-1xVEGF bispecific antibody has shown that it can extend patients’ lives.
A “statistically significant and clinically meaningful” overall survival (OS) benefit has been observed in the final analysis of ivonescimab’s phase 3 HARMONi-A study, Akeso said Tuesday in its half-year report (PDF).
“As the first phase 3 final analysis for ivonescimab, these results not only reinforce its breakthrough value in progression-free survival (PFS), but also highlight its ability to deliver significant OS improvement, a key endpoint in global oncology drug development,” Akeso said in an Aug. 26 press release.
The China-only study supported ivonescimab’s very first approval in China last year. The trial tested the bispecific antibody alongside chemotherapy for the treatment of patients with EGFR-mutated, nonsquamous non-small cell lung cancer who have progressed after tyrosine kinase inhibitor therapy.
Detailed results from this study will be presented at an upcoming medical conference, Akeso said in the report.
Previously, the HARMONi-A trial showed that ivonescimab, used on top of chemo, slashed patients’ risk of progression or death by 54% compared with chemo alone.
Despite widespread enthusiasm about the PD-(L)1xVEGF approach, the question of whether ivonescimab’s observed tumor progression benefits would translate into longer life expectancy has lingered over the treatment.
Meeting the gold-standard overall survival endpoint is “an important accomplishment,” Evercore ISI analysts wrote in a Monday note to clients.
Industry watchers had little hope for HARMONi-A to meet statistical significance on the OS endpoint because the drug’s effect appeared to be deteriorating in previous disclosures. A 28% death risk reduction at 30% of data maturity later shrank to 20% after 52% maturity during two previous interim analyses.
“Hitting stat sig OS here reinforces the idea that the therapy offers durable benefits,” the Evercore analysts explained.
What’s more important, the positive readout increases the chances that a global trial, HARMONi, could eventually meet overall survival, as well, with longer follow-up, the Evercore team added.
Some patients from HARMONi-A were included in the global HARMONi trial, which recently also met its progression-free survival endpoint in second-line EGFR-mutated NSCLC.
In its May announcement of that HARMONi result, Akeso’s U.S. partner Summit disappointed investors as a 21% reduction in the risk of death for ivonescimab narrowly missed statistical significance at an interim analysis.
At that time, Summit noted that the median follow-up time for Western patients was less than the median OS length for all patients, suggesting that additional time may be needed for the data to mature.
Summit has said it intends to seek an FDA approval based on the HARMONi results but will “consider the timing” because the agency indicated that a statistically significant survival benefit is necessary to support a marketing authorization.
If HARMONi eventually meets its overall survival goal, it would help clarify another key question surrounding ivonescimab—whether its benefits in Chinese patients can be replicated in Western populations.
Akeso and Summit are also awaiting more important readouts from HARMONi-2, -3 and -7 in different first-line NSCLC settings. Among them, the high-profile HARMONi-2 trial testing ivonescimab head to head against Merck & Co.’s Keytruda in PD-L1-positive NSCLC has performed an unplanned overall survival analysis at the request of Chinese regulators, and investors were split on its results.
Akeso will host a conference call on Wednesday (China Standard Time) to discuss its half-year results.