Ivonescimab Wins NMPA Approval in China for First-Line, PD-L1+ Advanced NSCLC

Image Credit: © catalin
– stock.adobe.com

China’s National Medical Products Administration (NMPA) has approved ivonescimab for use as a monotherapy in the first-line treatment of patients with advanced, PD-L1–positive (tumor proportion score ≥1%) non–small cell lung cancer (NSCLC) who do not harbor EGFR or ALK mutations.1

The approval was supported by data from the phase 3 HARMONi-2 trial (NCT05499390), which showed that patients treated with ivonescimab (n = 198) achieved a median progression-free survival (PFS) of 11.1 months compared with 5.8 months for patients treated with pembrolizumab (Keytruda; n = 200; stratified HR, 0.51; 95% CI, 0.38-0.69; one-sided P < .0001).2

An interim analysis of overall survival (OS) conducted with data at 39% maturity showed that ivonescimab produced a clinically meaningful improvement in OS (HR, 0.777).1,3

"The phase 3 HARMONi-2 study demonstrated that ivonescimab offers significant improvements in PFS and OS compared [with] pembrolizumab. This breakthrough provides a safer and more effective first-line treatment option for NSCLC, particularly beneficial for patients who need better efficacy or quality of life, or those who are not suitable for chemotherapy due to its [adverse] effects,” Zhou Caicun, MD, principal investigator of the HARMONi-2 trial, and director of the Department of Oncology at the Shanghai East Hospital of Tongji University, stated in a news release.

HARMONi-2 Deep Dive

The randomized, multicenter, double-blind trial enrolled patients at least 18 years of age with histologically or cytologically confirmed stage IIIB/C or IV NSCLC who received no prior systemic therapy in the locally advanced or metastatic setting.4 Patients were required to have positive PD-L1 expression in tumor tissue, and the presence of EGFR or ALK mutations precluded patients from enrollment.

Other key inclusion criteria consisted of an ECOG performance status of 0 or 1; a life expectancy of at least 3 months; measurable disease per RECIST 1.1 criteria; adequate organ function; and recovery from effects of prior radiotherapy or surgery.

Investigators excluded patients with any histologically confirmed small cell carcinoma component; those with immunodeficiency or were receiving systemic steroid therapy within 2 years prior to enrollment; those who underwent major surgery within 30 days of study entry; patients with known, active central nervous system metastases; those with an active autoimmune disease requiring systemic treatment in the past 2 years; and patients with active infections requiring systemic therapy.

Patients were randomly assigned 1:1 to receive ivonescimab at 20 mg/kg or pembrolizumab at 200 mg once every 3 weeks.2

PFS served as the trial’s primary end point. Secondary end points included OS, overall response rate, duration of response, disease control rate, time to response, and safety.

Regarding safety, grade 3 or higher treatment-related AEs were reported 29% of patients in the ivonescimab arm (n = 197) vs 16% of patients in the pembrolizumab group (n = 199).2 The rates of grade 3 or higher immune-related AEs occurred at rates of 7% and 8%, respectively.

"We are thrilled to announce the approval of ivonescimab as a first-line treatment for PD-L1–positive NSCLC, a major breakthrough in cancer immunotherapy,” Xia Yu, PhD, founder, chairwoman, president, and chief executive officer of Akeso, added in a news release.1 “This milestone is a result of the dedication of investigators, participants, and patients, and we sincerely thank all of them. We also appreciate the regulatory authorities for their efficient and diligent review, which enables us to offer this new treatment to patients in China.

In May 2024, the NMPA approved ivonescimab in combination with chemotherapy for previously treated patients with advanced NSCLC harboring EGFR mutations.5

References

1. Ivonescimab receives NMPA approval for first-line treatment of PD-L1-positive NSCLC, based on breakthrough head to head phase III trial demonstrating superior efficacy over pembrolizumab. News release. Akeso. April 25, 2025. Accessed April 28, 2025. https://www.akesobio.com/en/media/akeso-news/250426/
2. Xiong A, Wang L, Chen J, et al. Ivonescimab versus pembrolizumab for PD-L1-positive non-small cell lung cancer (HARMONi-2): a randomised, double-blind, phase 3 study in China. Lancet. 2025;405(10481):839-849. doi:10.1016/S0140-6736(24)02722-3
3. Interim overall survival analysis requested from Chinese health authorities shows a clinically meaningful, positive trend favoring ivonescimab compared to pembrolizumab in PD-L1 positive advanced NSCLC from HARMONi-2 study conducted by Akeso in China. News release. Summit Therapeutics. April 25, 2025. Accessed April 28, 2025. https://www.smmttx.com/wp-content/uploads/2025/04/2025_PR_0425_Ivonescimab-AK112-303-Approval-_-FINAL.pdf
4. AK112 in advanced non-small cell lung cancer. ClinicalTrials.gov. Updated March 5, 2025. Accessed April 28, 2025. https://clinicaltrials.gov/study/NCT05499390
5. Ivonescimab in combination with chemotherapy approved in China by NMPA for 2L+ EGFRm NSCLC based on HARMONi-A clinical trial: positive trend observed in overall survival towards ivonescimab plus chemotherapy. News release. May 31, 2024. Accessed April 28, 2025. https://www.akesobio.com/en/media/akeso-news/240531/