Ivonescimab's Emerging Role in First-Line Squamous NSCLC Treatment: A Market-Transforming Opportunity in Oncology Immunotherapy

The oncology immunotherapy landscape in China is on the cusp of a paradigm shift, driven by the emergence of Ivonescimab—a first-in-class PD-1/VEGF bispecific antibody—as a transformative first-line treatment for advanced squamous non–small cell lung cancer (sq-NSCLC). With the HARMONi-6 Phase III trial results set to be presented as a Late-Breaking Abstract (LBA) at the 2025 European Society for Medical Oncology (ESMO) Annual Congress, the drug's clinical and commercial potential is gaining unprecedented momentum. This analysis explores how Ivonescimab's groundbreaking performance in HARMONi-6 could redefine treatment standards, disrupt existing market dynamics, and unlock billions in revenue for investors.

Clinical Breakthrough: HARMONi-6 Trial Outcomes and Regulatory Momentum

The HARMONi-6 trial, which enrolled 532 patients with advanced sq-NSCLC, demonstrated statistically significant and clinically meaningful improvements in progression-free survival (PFS) for Ivonescimab combined with chemotherapy compared to tislelizumab plus chemotherapy. The Independent Data Monitoring Committee (IDMC) confirmed these results in April 2025, with the primary endpoint met across all subgroups, including PD-L1–positive and PD-L1–negative populationsIvonescimab HARMONi-6 Results Selected for ESMO 2025 LBA;^[1]. Notably, the safety profile of Ivonescimab was comparable to the control group, with no new safety signals identifiedIvonescimab in Combination with Chemotherapy Demonstrates …^[2].

These findings have already triggered regulatory action: in July 2025, China's National Medical Products Administration (NMPA) accepted a supplemental New Drug Application (sNDA) for Ivonescimab in combination with chemotherapy for first-line sq-NSCLC treatmentChina’s NMPA Accepts sNDA for Ivonescimab Plus …^[3]. The ESMO 2025 presentation, scheduled for October 19, 2025, will further validate these results on a global stage, potentially accelerating adoption and reimbursement decisionsHARMONi-6, Featuring Ivonescimab Combined with …^[4].

Market Dynamics: A Growing Opportunity in Squamous NSCLC

The China squamous NSCLC therapeutics market is a high-growth segment within the broader NSCLC landscape. By 2025, the global NSCLC therapeutics market is valued at $21.45 billion and projected to reach $43.89 billion by 2030, with China's domestic market expected to grow at a compound annual growth rate (CAGR) of 13.6% from $1.098 billion in 2025 to $2.081 billion by 2030Non-small Cell Lung Cancer Therapeutics Market Report 2030^[5]. This growth is fueled by rising lung cancer incidence, particularly in regions with high smoking prevalence, and the adoption of innovative therapies like immunotherapies and bispecific antibodies.

Ivonescimab's unique mechanism—simultaneously targeting PD-1 and VEGF pathways—positions it to address unmet needs in sq-NSCLC, where resistance to PD-1/PD-L1 inhibitors remains a challengeEfficacy and Safety of Ivonescimab in the Treatment of Advanced Non-small Cell Lung Cancer (NSCLC): A Systematic Review^[6]. Unlike monotherapies or combinations with single-pathway inhibitors, Ivonescimab's dual targeting may overcome tumor evasion strategies, offering durable responses and improved survival outcomesIvonescimab Plus Chemotherapy Demonstrates Statistically …^[7].

Competitive Landscape: Disrupting PD-1 Inhibitors

The current market for sq-NSCLC in China is dominated by PD-1 inhibitors such as tislelizumab (included in the National Reimbursement Drug List) and penpulimab. However, Ivonescimab's head-to-head superiority in HARMONi-6 could erode these competitors' market shares. For instance, tislelizumab's median PFS in real-world studies is 11.3 monthsComparison of the efficacy and safety of …^[8], while penpulimab's cost-effectiveness ratio of $16,105.90 per quality-adjusted life year (QALY) is favorable but limited by its absence from the National Reimbursement Drug List (NRDL)Cost-effectiveness analysis of penpulimab combined with …^[9].

Ivonescimab's potential inclusion in the NRDL post-approval could further enhance its accessibility. Given its demonstrated 49% reduction in progression risk compared to pembrolizumab in PD-L1–high tumorsSummit Therapeutics: Multibillion Dollar NSCLC …^[10], payers may prioritize its adoption through value-based contracts tied to real-world PFS outcomesNon-Small Cell Lung Cancer Market Size & Share Analysis^[11]. This could create a pricing premium for Ivonescimab, given its superior efficacy, while existing PD-1 inhibitors face downward pressure due to competition.

Financial and Strategic Implications for Investors

The commercial potential of Ivonescimab is vast. Assuming a 20% market share in the first-line sq-NSCLC segment by 2030, and with treatment costs for PD-1 inhibitors averaging $4,265 per monthPrice trends and affordability of metastatic non–small cell lung cancer (NSCLC) targeted drugs in China from 2019 to 2024^[12], Ivonescimab could generate annual revenues exceeding $400 million in China alone. Broader applications, such as second-line therapy and combinations with other modalities, could further expand its addressable marketIvonescimab in Combination with Chemotherapy Achieves^[13].

For Summit Therapeutics, Akeso, and other stakeholders, the drug's approval in China represents a critical inflection point. The company's recent sNDA acceptance and ESMO 2025 presentation signal strong regulatory and scientific validation, reducing commercial risks for investors. Additionally, the drug's bispecific platform offers a scalable foundation for future indications, enhancing long-term value.

Conclusion: A New Era in Squamous NSCLC Treatment

Ivonescimab's emergence as a first-line therapy for sq-NSCLC marks a pivotal moment in oncology immunotherapy. By combining clinical superiority, regulatory momentum, and a favorable safety profile, the drug is poised to disrupt the market dominated by PD-1 inhibitors. For investors, the alignment of clinical innovation, growing market demand, and strategic regulatory pathways presents a compelling opportunity to capitalize on a transformative therapy. As the ESMO 2025 presentation approaches, the oncology community and capital markets will be watching closely to see how this new standard of care reshapes the future of lung cancer treatment.