Advanced NSCLC | Image by Ashling Wahner
& MJH Life Sciences Using
China’s National Medical Products Administration (NMPA) has accepted a supplemental new drug application (sNDA) seeking the approval of ivonescimab for use in combination with chemotherapy for the treatment of patients with advanced squamous non–small cell lung cancer (NSCLC).1
The sNDA is based on findings from the phase 3 HARMONi-6/AK112-306 trial (NCT05840016) showing a clinically meaningful and statistically significant improvement in progression-free survival (PFS) with the regimen vs tislelizumab-jsgr (Tevimbra) plus chemotherapy in this patient population.2 In April 2025, the developer, Akeso, Inc., announced that an independent data monitoring committee had determined that the trial had met its primary end point of PFS in the intention-to-treat population (n = 532) at the first prespecified interim analysis.2
According to the news release, data also indicated that the addition of ivonescimab to chemotherapy resulted in a clinically meaningful benefit in PFS vs tislelizumab plus chemotherapy in the PD-L1–positive and PD-L1–negative populations.
“Ivonescimab has gained widespread recognition for treating [patients with] EGFR TKI–resistant, advanced nonsquamous NSCLC since its approval in China nearly a year ago,” Shun Lu, MD, PhD, director of Shanghai Lung Cancer, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, and principal investigator of the HARMONi-6 study, stated in a news release.
“The [phase 3] HARMONi-2 study [NCT05499390] showed strong positive results for PD-L1–positive squamous and nonsquamous 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 nonsquamous cancers.”
The HARMONi-6 trial was designed to evaluate the relative efficacy of PD-1 inhibitors in combination with chemotherapy. The study enrolled patients between the ages of 18 and 75 who had received a histologically confirmed diagnosis of stage IIIB/C or IV squamous NSCLC.3 Additional eligibility criteria stipulated that patients had to have an ECOG performance status of 0 or 1, life expectancy of at least 3 months, measurable disease per RECIST 1.1 criteria, and adequate organ function. Prior systemic antitumor therapy for locally advanced or metastatic NSCLC was not allowed.
Notably, approximately 63% of enrolled patients had centrally located squamous cell carcinoma, mirroring real-world distribution.2
Patients were randomly assigned to receive ivonescimab intravenously (IV) once every 3 weeks or tislelizumab IV at 200 mg once every 3 weeks.3 Patients in the investigational and control arms also received 4 cycles of chemotherapy consisting of carboplatin at area under the curve 5 once every 3 weeks and paclitaxel at 175 mg/m2 once every 3 weeks.
In addition to the primary end point of PFS, secondary end points included overall survival, overall response rate, duration of response, disease control rate, time to response, and safety. Additional end points subject to evaluation include the number of patients with detectable anti-drug antibodies, longitudinal assessment of serum drug concentration after administration, and the relationship between PD-L1 expression level and efficacy.
With respect to safety, the incidence of treatment-related serious adverse effects and grade 3 or higher bleeding events were similar between the investigational and control arms. Ivonescimab resulted in a favorable safety profile, and no new adverse effects were reported.
“This positions ivonescimab as a new standard of care for the treatment of these types of cancer. I am confident and excited about its potential in global phase 3 trials and its ability to positively reshape the global oncology landscape with a Chinese solution,” Lu added.2
Full results from the trial are expected to be presented at an upcoming medical meeting this year.
References
- NMPA accepts sNDA for ivonescimab in combination with chemotherapy as first-line treatment for advanced squamous non-small cell lung cancer. News release. Akeso, Inc. July 28, 2025. Accessed July 31, 2025. https://www.akesobio.com/en/media/akeso-news/250728/
- 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. News Release. Akeso. April 23, 2025. Accessed July 31, 2025. https://www.akesobio.com/en/media/akeso-news/250423/
- AK112 in combination with chemotherapy in advanced squamous non-small cell lung cancer. ClinicalTrials.gov. Updated August 23, 2023. Accessed July 31, 2025. https://clinicaltrials.gov/study/NCT05840016