Advanced squamous NSCLC remains an area of significant unmet need, with limited targeted treatment options and continued reliance on chemotherapy and immunotherapy combinations. Ivonescimab (SMT112 in Summit’s licensed territories and AK112 elsewhere) is a novel, potential first-in-class PD-1/VEGF bispecific antibody designed to combine immune checkpoint inhibition with anti-angiogenic activity in a single molecule. Developed by Akeso and currently being evaluated across multiple Phase III trials, ivonescimab has emerged as a promising new therapeutic approach. 

In the Phase III HARMONi-6 trial, ivonescimab plus chemotherapy previously achieved a statistically significant and clinically meaningful improvement in progression-free survival versus tislelizumab plus chemotherapy, meeting the study’s primary endpoint. Building on these results, the overall survival analysis presented at ASCO 2026 confirmed that the PFS advantage translated into a significant survival benefit, further reinforcing ivonescimab’s potential to reshape the first-line treatment landscape for advanced squamous NSCLC.

Efficacy Results:

Safety:

• The safety profile of ivonescimab plus chemotherapy was manageable and consistent with previous studies, with no new safety signals identified. 

• Treatment-related serious adverse events occurred in 41.4% of patients receiving ivonescimab in combination with chemotherapy and 34.3% of patients receiving tislelizumab in combination with chemotherapy.

• Most VEGF-related adverse events in the ivonescimab arm were Grade 1–2 in severity. 

• Grade ≥3 hemorrhage events occurred in 2.6% of patients receiving ivonescimab plus chemotherapy versus 0.8% with tislelizumab plus chemotherapy. 

• Treatment-related adverse events leading to discontinuation were low and comparable between arms (5.3% vs 4.5%). 

• Overall tolerability remained favorable despite the addition of VEGF-targeting activity.

KOL insights

“For the first time, a Phase III study has demonstrated a statistically significant overall survival benefit over a PD-1 inhibitor plus chemotherapy regimen in first-line driver mutation-negative NSCLC. These results confirm that ivonescimab's previously observed PFS advantage translates into a meaningful survival benefit, reinforcing its potential to improve outcomes beyond current immunotherapy-based standards.” –Expert Opinion

“In previously untreated advanced squamous NSCLC, the Phase III HARMONi-6 trial demonstrated a significant overall survival benefit with ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy, marking the first regimen to show superiority over an active PD-1 inhibitor-based control in the first-line setting.”–Expert Opinion

Conclusion: 

From a competitive perspective, ivonescimab enters a crowded but rapidly evolving NSCLC landscape currently dominated by PD-1/PD-L1 inhibitors such as KEYTRUDA, TEVIMBRA, and OPDIVO. Emerging challengers include next-generation immunotherapy combinations, bispecific antibodies, and antibody-drug conjugates (ADCs) being developed by companies such as Summit Therapeutics, Akeso, Merck, AstraZeneca, and BioNTech. If the survival benefit is replicated globally, ivonescimab could emerge as one of the most formidable competitors to established PD-1-based regimens and potentially set a new benchmark for first-line advanced squamous NSCLC.

The Phase III HARMONi-6 trial marks a significant milestone for ivonescimab and highlights the growing innovation emerging from China's biotech sector. ecent findings make ivonescimab the first regimen to show a statistically significant overall survival advantage over a PD-1 inhibitor plus chemotherapy standard in first-line squamous NSCLC, validating its novel mechanism and reinforcing its potential to redefine frontline treatment. While confirmation in ongoing global HARMONi studies is needed, the results position ivonescimab as a promising new contender in the evolving NSCLC landscape.