Akeso's ivonescimab extends survival in PD-L1+ lung cancer

Akeso and Summit's PD-1xVEGF drug ivonescimab has improved overall survival (OS) in another phase 3 trial, this time when used as a first-line treatment for PD-L1-positive non-small cell lung cancer (NSCLC).

The results come from the HARMONi-2 trial carried out in China, where ivonescimab is already approved as a monotherapy for PD-L1+ non-squamous NSCLC on the strength of progression-free survival (PFS) data from the study.

In data presented at the 2024 World Conference on Lung Cancer (WCLC), ivonescimab had nearly doubled PFS compared to MSD's PD-L1 inhibitor Keytruda (pembrolizumab) – which has been the cornerstone of upfront treatment of PD-L1–expressing NSCLC for years – extending it from 5.82 months to 11.14 months.

The OS result has not yet been revealed, but is "statistically significant and clinically meaningful" compared to Keytruda, according to Akeso and SUMMIT, which said this is the first phase 3 trial to show an improvement over MSD's drug in this setting.

OS is considered a more robust measure of efficacy than PFS, and extending it makes a more powerful case for approval and reimbursement decisions.

Ivonescimab is also approved in China as a second-line therapy for EGFR-mutated non-squamous NSCLC based on the HARMONi trial, and as a first-line treatment for squamous NSCLC in combination with chemotherapy based on the HARMONi-6 study.

The latest readout also comes ahead of regulatory decisions in other markets, including a US FDA verdict due in November on EGFR-mutated non-squamous NSCLC, which could spearhead the drug's rollout in international markets.

Ivonescimab was the source of considerable excitement after showing improved OS compared to $32 billion-a-year blockbuster Keytruda in a Chinese NSCLC population, and prompted a series of multibillion-dollar licensing deals involving other VEGFxPD-(L)1 assets.

While that initial enthusiasm was dampened after data from HARMONi suggested it was less impressive in international patients, significant OS improvements in HARMONi-6, HARMONi-GI1 in biliary tract cancer, and now HARMONi-2 have restored some of ivonescimab's lustre.

There are still some big question marks over the drug, however, as there have been signs that the efficacy in HARMONi-6 is deteriorating with extended follow-up, while an interim data drop from the international HARMONi-3 study in first-line NSCLC – involving both squamous and non-squamous tumours – missed a PFS endpoint and added to fears it may have lesser efficacy in Western, compared to Chinese, cohorts.

Now, all eyes are on the prospect of additional PFS and initial OS data from HARMONi-3, due before the end of the year, which should give a clearer indication of ivonescimab's potential internationally.

Summit, meanwhile, which has rights to the drug outside Greater China, is also running the HARMONi-7 study comparing the drug to first-line Keytruda in an international cohort of PD-L1+ NSCLC patients.

Summit licensed rights to ivonescimab in a $5 billion deal – including a whopping $500 million upfront – in 2022.