China’s NMPA Accepts sBLA for Ivonescimab in First-Line PD-L1+ NSCLC

China’s National Medical Products Administration (NMPA) has accepted a supplemental biologics license application (sBLA) seeking the approval of ivonescimab (AK112; SMT112) monotherapy for the first-line treatment of patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) who have a PD-L1 tumor proportion score (TPS) of at least 1%.¹

The sBLA is supported by data from the phase 3 HARMONi-2 trial (NCT05499390), which showed that treatment with ivonescimab led to a statistically significant and clinically meaningful improvement in progression-free survival (PFS) vs pembrolizumab (Keytruda) in patients with locally advanced or metastatic, PD-L1–positive NSCLC. A prespecified interim analysis demonstrated that the PFS benefit was observed across various subgroups, including those with a PD-L1 TPS of 1% to 49%; those with a PD-L1 TPS of at least 50%; those with squamous or nonsquamous histology; and those with other high-risk features.²

"As a researcher and clinician, we eagerly anticipate ivonescimab becoming the new standard treatment for first-line lung cancer, providing a superior 'chemotherapy-free' option for patients," Zhou Caicun, MD, PhD, principal investigator of the HARMONi-2 study and director of the Oncology Department at East Hospital Affiliated To Tongji University, in Shanghai, China, stated in a news release.1 "The success of the HARMONi-2 study underscores the immense value of ivonescimab's synergistic dual anti-tumor mechanism of 'tumor immunotherapy plus anti-angiogenesis.'”

Ivonescimab is a novel, potential first-in-class investigational bispecific antibody directed at PD-1 and VEGF.

HARMONi-2 was a multicenter, randomized, controlled trial that enrolled patients at least 18 years of age with histologically or cytologically confirmed stage IIIB/C or IV NSCLC who had a positive PD-L1 expression on tumor tissue.Other key inclusion criteria consisted of a life expectancy of at least 3 months; an ECOG performance status of 0 or 1; measurable disease per RECIST 1.1 criteria; and adequate organ function.³

Prior systemic therapy for locally advanced or metastatic NSCLC was not allowed, and patients could not have disease harboring EGFR mutations or ALK translocations. Other key exclusion criteria included any histologically confirmed small cell carcinoma component; a diagnosis of immunodeficiency or treatment with systemic steroids within 2 years of first study dose; major surgery within 30 days of enrollment; and known central nervous system metastases.

Eligible patients were randomly assigned to receive either intravenous (IV) ivonescimab at a selected dose or IV pembrolizumab at 200 mg once every 3 weeks.

Independent radiographic review committee (IRRC)–assessed PFS per RECIST 1.1 criteria served as the trial’s primary end point. Secondary end points included overall survival; IRRC- and investigator-assessed overall response rate, duration of response, disease control rate, and time to response; investigator-assessed PFS; and safety.

Safety data showed that ivonescimab was manageable, and its profile was consistent with treatments intended to inhibit PD-1 and VEGF.²

"We are thrilled that ivonescimab has achieved a significant milestone in first-line lung cancer therapy shortly after its approval for second-line treatment,” Michelle Xia, PhD, founder, chairwoman, president, and chief executive officer of Akeso, added in a news release.¹ “We sincerely thank all our colleagues at Akeso for their decade-long dedication and craftsmanship, the experts for their meticulous contributions, and all the participants involved in the projects."

The phase 3 HARMONi (NCT06396065) and HARMONi-3 (NCT05899608) trials are also investigating ivonescimab in patients with NSCLC. HARMONi is investigating ivonescimab plus chemotherapy vs placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic nonsquamous NSCLC who experienced disease progression after treatment with a third-generation EGFR TKI. HARMONi-3 is exploring ivonescimab plus chemotherapy vs pembrolizumab plus chemotherapy as first-line treatment for patients with metastatic squamous NSCLC.²

References

1. Akeso's sBLA for ivonescimab in 1L treatment of PD-L1 positive NSCLC accepted by NMPA. News release. Akeso. July 29, 2024. Accessed July 29, 2024. https://www.prnewswire.com/news-releases/akesos-sbla-for-ivonescimab-in-1l-treatment-of-pd-l1-positive-nsclc-accepted-by-nmpa-302208466.html
2. Ivonescimab monotherapy decisively beats pembrolizumab monotherapy head-to-head, achieves statistically significant superiority in PFS in first-line treatment of patients with PD-L1 positive NSCLC. News release. Akeso, Inc. May 30, 2024. Accessed July 29, 2024. https://www.prnewswire.com/news-releases/ivonescimab-monotherapy-decisively-beats-pembrolizumab-monotherapy-head-to-head-achieves-statistically-significant-superiority-in-pfs-in-first-line-treatment-of-patients-with-pd-l1-positive-nsclc-302159842.html
3. AK112 in advanced non-small cell lung cancer. ClinicalTrials.gov. Updated September 21, 2023. Accessed July 29, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT05499390