New Indication Approval (April 25, 2025): Approved by China’s National Medical Products Administration (NMPA) as a monotherapy for the first-line treatment of PD-L1 positive locally advanced or metastatic non-small cell lung cancer (NSCLC).
Previous Approval (May 2024): Initially approved in China for the second-line treatment of NSCLC.
Rapid Progression: The swift approval from second-line to first-line treatment within less than a year underscores its excellent efficacy.
Superior Efficacy (HARMONi-2 Study):
Head-to-Head Comparison: The HARMONi-2 study directly compared Ivonescimab (AK112) with Pembrolizumab (Keytruda, K药), a leading PD-1 inhibitor, as a first-line treatment for PD-L1 positive NSCLC.
Presentation: The study data was presented by Professor Zhou Caicun at the 2024 World Lung Cancer Congress, receiving significant acclaim.
Key Results (398 patients, 8.6 months follow-up):
Progression-Free Survival (PFS): Ivonescimab significantly improved median PFS by 91.4% compared to Keytruda (11.14 months vs. 5.82 months). AK112 reduced the risk of disease progression or death by 49%.
Objective Response Rate (ORR): Ivonescimab showed a higher ORR (50.0%) compared to Keytruda (38.5%).
Disease Control Rate (DCR): Ivonescimab also demonstrated a higher DCR (89.9%) compared to Keytruda (70.5%).
Uniqueness: Ivonescimab is currently the only anti-cancer drug globally to demonstrate superior efficacy over Keytruda in a head-to-head Phase III monotherapy clinical trial, in terms of both ORR and PFS.
Mechanism of Action (“Next-Generation” Immunotherapy):
Bispecific Antibody: Unlike traditional monoclonal antibodies, Ivonescimab is a bispecific antibody. It has two different antigen-binding regions sharing a common antibody constant region, allowing it to recognize two different tumor-associated antigens (PD-1 and VEGF).
Synergistic Effect: This dual targeting is hypothesized to offer a more potent and coordinated anti-tumor effect compared to single antibodies or combinations of two separate monoclonal antibodies.
Future Potential: The combination of PD-1 and VEGF targeting suggests that AK112 has the potential to replace traditional combination therapies involving PD-1 inhibitors and anti-VEGF drugs (like Avastin/Bevacizumab).
Safety Profile:
While Ivonescimab showed slightly higher rates of Grade 3 (severe) side effects compared to Keytruda, primarily attributed to its VEGF inhibition, the rates of serious adverse events were relatively similar.
Future Outlook:
Overall Survival (OS) data from the HARMONi-2 study is still maturing, but based on the strong PFS advantage, an impressive OS benefit is anticipated.
With ongoing global clinical studies, Ivonescimab is expected to continue bringing more positive surprises to cancer patients.
