Ivonescimab Plus Chemo Shows Stronger NSCLC Response Than Tislelizumab Combo

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First-line ivonescimab (SMT112), a first-in-class PD-1/VEGF bispecific antibody, plus chemotherapy led to strong responses compared with tisleizumab (Tevimbra) and chemotherapy in patients with advanced squamous non–small cell lung cancer (NSCLC), meeting the primary end point of progression-free survival (PFS) in the phase 3 AK112-306/HARMONi-6 study (NCT05840016).¹

At the first prespecified interim analysis, the combination of ivonescimab showed clinically meaningful PFS improvements in patients with PD-L1-positive and -negative populations. Additionally, ivonescimab had a favorable safety profile that was consistent with that observed in the control group.

Data from the study will be presented at a medical conference later this year.

“The interim analysis results from the HARMONi-6 study show that ivonescimab in combination with chemotherapy significantly prolonged progression-free survival compared to tislelizumab with chemotherapy…. [Ivonescimab] demonstrated a safety profile comparable to the control group. This highlights its potential to overcome the limitations of bevacizumab [Avastin] in treating squamous non–small cell lung cancer, ultimately enhancing the clinical benefits of immunotherapy for NSCLC. With its combined immune and antiangiogenic mechanisms, ivonescimab offers a promising new treatment option for patients with advanced squamous carcinoma,” said Lu Shun, professor, director of lung cancer at Shanghai Chest Hospital, Shanghai Jiao Ton University School of Medicine, and principal investigator of the study, in a press release.

A total of 532 patients were enrolled in HARMONi-6, with 63% of patients having centrally located squamous cell carcinoma. This is consistent with real-world patient populations.

About Ivonescimab

Ivonescimab is an investigational bispecific antibody targeting PD-1 and VEGF. It is currently approved by China’s National Medical Products Administration and is in clinical development in the US, Canada, Europe, Japan, and Latin America.²

Results from HARMONi-2 (NCT05499390) were published in The Lancet in March 2025. Here, ivonescimab significantly improved PFS compared with pembrolizumab (Keytruda) in patients with previously untreated advanced PD-L1-positive NSCLC.³ The median PFS with ivonescimab was 11.1 months vs 5.8 months with pembrolizumab (HR, 0.51; 95% CI, 0.38-0.68; 1-sided P <.0001). The PFS improvement was consistent across prespecified subgroups of PD-L1 expression. Among patients with squamous cell carcinoma, the incidence of grade 3 or higher adverse events were consistent across the treatment arms.

“Ivonescimab has gained widespread recognition for treating EGFR-[tyrosine kinase inhibitor (TKI)]-resistant, advanced [nonsquamous] NSCLC since its approval in China nearly a year ago. The HARMONi-2 study showed strong positive results for PD-L1-positive squamous and nonsquamous NSCLC in first-line treatment,” added Shun in the press release.¹

REFERENCES:

1. Ivonescimab in combination with chemotherapy demonstrates statistically significant and strong positive results in first-line treatment of squamous non-small cell lung cancer (sq-NSCLC) vs. tislelizumab in combination with chemotherapy. News release. Akesobio. April 23, 2025. Accessed April 23, 2025. https://tinyurl.com/4k9veryy

2. Ivonescimab overview. Summit Therapeutics. Accessed April 23, 2025. https://tinyurl.com/mrx3kszb

3. Xiong A, Wang L, Chen J, et al. Ivonescimab versus pembrolizumab for PD-L1-positive non-small cell lung cancer (HARMONi-2): a randomized, double-blind, phase 3 study in China. Lancet. 2025;405(10481):839-849. doi:10.1016/S0140-6736(24)02722-3