Akeso presented final survival trial data for its PD-(L)1×VEGF bispecific antibody ivonescimab in EGFR-mutated nonsquamous non-small cell lung cancer (nsq-NSCLC) at the 40th Annual Meeting of the Society for Immunotherapy of Cancer (SITC 2025) held in National Harbor, Maryland, on November 7, 2025.
Results from the Phase III HARMONi-A study, with patients from China only, showed that ivonescimab plus chemotherapy versus chemotherapy alone in patients with EGFR-mutated nsq-NSCLC whose disease had progressed on EGFR tyrosine kinase inhibitors (TKIs) led to statistically significant and clinically meaningful improvements in both progression-free (PFS) and overall survival (OS).
The ivonescimab + chemo arm achieved a median OS of 16.8 months versus 14.1 months in the chemo-alone arm.
This is the first time a trial of a PD-(L)1×VEGF bispecific has met the “gold-standard” OS endpoint in any indication.
Over a median follow-up of 32.5 months, the OS benefit of the ivonescimab combo was consistent across all subgroups, showing significant improvement regardless of the presence of brain metastases or EGFR mutations (19Del and L858R), according to Akeso.
The final analysis also showed that adding ivonescimab to chemotherapy cut the risk of death by 26% in patients with EGFR-mutated nsq-NSCLC who had previously received an EGFR inhibitor.
The trial was conducted in China, where Akeso is headquartered in the city of Zhongshan.
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Ivonescimab is already approved in China (May 2024) and included on China’s National Reimbursement Drug List (NRDL, November 2024).
Since the HARMONi-A trial was China-only, and while results are encouraging, it remains to be seen whether the same trial outcomes will translate into Western/regional populations.
Summit Therapeutics holds the rights to the drug in the US, Europe, Canada and Japan.
Despite final OS data still pending outside of China, Summit is planning to go ahead and submit a Biologics License Application (BLA) in Q4 2025 based on the Chinese results.
Patients with EGFR-mutated nsq-NSCLC who have progressed on EGFR-TKIs have historically had limited benefit from immune checkpoint inhibitors, and OS gains in this setting have been elusive.
Ivonescimab is engineered as a bispecific antibody targeting both PD-1 and VEGF pathways, with a tetravalent design that may enhance tumor microenvironment targeting.
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Summit and Akeso not only face a smaller niche (EGFR-mut NSCLC post-TKI), but also a competitive space that includes ADCs (antibody-drug conjugates).
Merck remains a key competitive force in the market through its PD-1 inhibitor oncology backbone Keytruda (pembrolizumab) and its expanding immuno-oncology combination strategy, including partnerships and pipeline assets targeting VEGF and tumor microenvironment pathways.
While Keytruda monotherapy has historically struggled in EGFR-mutant NSCLC, Merck is advancing combination regimens and next-generation immuno-oncology approaches that could challenge bispecific entrants like ivonescimab in both metastatic and earlier-line settings.
Given that EGFR-mutant NSCLC is generally less responsive to immunotherapy, PD-(L)1×VEGF bispecifics could pose an edge over anti-PD-1 drugs like Keytruda.
Others to watch out for on the horizon include Kelun-Biotech’s ADC candidate. The China-based company reported Phase III results for sacituzumab tirumotecan (sac-TMT), its TROP2 ADC partnered with Merck, showing a 40% reduction in the risk of death versus chemotherapy in Chinese patients with previously treated EGFR-mutant NSCLC. Unlike ivonescimab, which was tested in combination with chemotherapy, the ADC delivered this benefit as a monotherapy.
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