Akeso’s PD-1/VEGF Bispecific Antibody Demonstrates Meaningful Progression-Free Survival Benefits in Advanced Squamous NSCLC

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Ivonescimab plus chemotherapy demonstrated statistically significant and clinically meaningful improvements in progression-free survival (PFS) compared to tislelizumab plus chemotherapy in the first-line treatment of advanced squamous non-small cell lung cancer (sq-NSCLC), according to interim results from the Phase III HARMONi-6 trial show. Full results from the trial evaluating Akeso’s first-in-class PD-1/VEGF bispecific antibody are expected to be presented later this year at a medical conference.¹

"The interim analysis results from the HARMONi-6 study show that ivonescimab in combination with chemotherapy significantly prolonged PFS compared to tislelizumab with chemotherapy,” principal trial investigator Lu Shun, director, Shanghai lung cancer, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, said in a press release.

The HARMONi-6 trial was conducted across 66 centers in China and included 532 patients with sq-NSCLC, 63% of whom had centrally located squamous cell carcinoma. The study’s primary endpoint was PFS at the first pre-specified interim analysis.

Ivonescimab showed meaningful PFS benefits in both PD-L1-positive and PD-L1-negative patient populations. Additionally, the combination of ivonescimab and chemotherapy significantly outperformed tislelizumab plus chemotherapy in the intent-to-treat population. Ivonescimab was found to have a favorable safety profile, with no new safety signals identified. The occurrence of treatment-emergent adverse effects and grade 3 or higher bleeding events was similar between the ivonescimab group and the control group.¹

“In patients with up to 63% central squamous carcinoma, ivonescimab demonstrated a safety profile comparable to the control group,” added Shun, in the press release. “This highlights its potential to overcome the limitations of bevacizumab 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."

According to Akeso, the HARMONi-6 trial marks ivonescimab’s third Phase III success in lung cancer and its second head-to-head win over a PD-1 inhibitor.1 Currently, the treatment is approved in China for epidermal growth factor receptor tyrosine kinase inhibitor-resistant, non-squamous (nsq) NSCLC, with a supplemental New Drug Application as a monotherapy for the first-line treatment of PD-L1-positive NSCLC currently under review.²

"Ivonescimab has gained widespread recognition for treating EGFR-TKI-resistant, advanced nsq-NSCLC since its approval in China nearly a year ago,” added Lu, in the press release. “The HARMONi-2 study showed strong positive results for PD-L1-positive squamous and non-squamous NSCLC in first-line treatment. Additionally, the recent HARMONi-6 study demonstrated significant positive outcomes in first-line squamous NSCLC, further confirming ivonescimab's exceptional efficacy in both squamous and non-squamous cancers.”

According to the World Cancer Research Fund, lung cancer is the most common form of cancer globally. It is the most common form of cancer in men and the second most common in women. In 2022, China had the highest number of people with lung cancer, at just over 1 million. In a distant second, the United States had approximately 226,000.³

"Today, we are incredibly excited to announce the third significant positive result for ivonescimab in a Phase III study,” said Xia Yu, founder, chairwoman, president, CEO, Akeso, in the press release. “PD-1 combined with chemotherapy remains the global standard of care for first-line treatment of NSCLC. Ivonescimab has once again demonstrated its breakthrough clinical value and market competitiveness as a next-generation cancer therapy through compelling clinical data. We sincerely thank all the investigators, participants, and patients who have contributed to this clinical study."

References

1. Ivonescimab in Combination with Chemotherapy Demonstrates Statistically Significant and Strongly Positive Results in First-Line Treatment of Squamous Non-Small Cell Lung Cancer (sq-NSCLC) vs. Tislelizumab in Combination with Chemotherapy. PR Newswire. April 22, 2025. Accessed April 23, 2025. https://prnmedia.prnewswire.com/news-releases/ivonescimab-in-combination-with-chemotherapy-demonstrates-statistically-significant-and-strongly-positive-results-in-first-line-treatment-of-squamous-non-small-cell-lung-cancer-sq-nsclc-vs-tislelizumab-in-combination-with-chemo-302435143.html

2. Akeso Announces the Completion of Patient Enrollment in the Phase III Clinical Trial (HARMONi-6) Comparing Ivonescimab and Tislelizumab for First-Line Treatment of Sq-NSCLC. PR Newswire. February 5, 2025. Accessed April 23, 2025. https://www.prnewswire.com/news-releases/akeso-announces-the-completion-of-patient-enrollment-in-the-phase-iii-clinical-trial-harmoni-6-comparing-ivonescimab-and-tislelizumab-for-first-line-treatment-of-sq-nsclc-302369543.html

3. Lung cancer statistics. WCRF. Accessed April 23, 2025. https://www.wcrf.org/preventing-cancer/cancer-statistics/lung-cancer-statistics/