The latest results from the HARMONi-6 study showed that treatment of advanced squamous non-small cell lung cancer (NSCLC) with ivonescimab plus chemotherapy increases overall survival, in addition to improving progression-free survival, compared to a current treatment of tislelizumab plus chemotherapy.

Use of ivonescimab was not limited by PD-L1 levels—it extends life even in people whose cancer has very little or no PD-L1 protein.

The research was presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, taking place May 29 to June 2 in Chicago. 

“Squamous non-small cell lung cancer is associated with worse clinical outcomes than non-squamous non-small cell lung cancer. This is one of very few studies in advanced squamous non-small cell lung cancer that has shown median survival beyond 2 years,” said lead study author Shun Lu, MD, PhD, Shanghai Chest Hospital, Jiao Tong University School of Medicine, Shanghai, China.

Squamous NSCLC generally has fewer treatment options than other types of NSCLC.

Combining therapies into a bispecific antibody that simultaneously targets two key mechanisms of cancer cell activity could fix some of the issues by concentrating the treatment effects on cancerous cells. 

The phase 3 HARMONi-6 study was designed to compare how well the anti-PD-1/VEGF bispecific antibody ivonescimab with chemotherapy prevents squamous NSCLC growth compared to tislelizumab, a checkpoint inhibitor, with chemotherapy.

It also looked at the health issues associated with the treatments and how long people live after being treated.

The trial included 532 people with advanced (stage IIIB, IIIC, or IV) squamous NSCLC.

For first-line treatment, 266 received ivonescimab and the chemotherapies paclitaxel and carboplatin.

The 266 people in the control group received tislelizumab and the same chemotherapies.

Earlier results from the trial showed that ivonescimab kept squamous NSCLC from growing for longer than tislelizumab: Progression-free survival (PFS) was about 11 months compared to 9 months.

Key Findings

• The improvement in PFS was an indicator for overall survival (OS) results: After a median follow-up of 21.4 months, the median OS after ivonescimab and chemotherapy treatment was about 28 months, compared to 24 months with tislelizumab and chemotherapy.  
• Over the study period, ivonescimab treatment reduced the risk of death by 34%.
• As expected, tislelizumab was less effective when PD-L1 levels were low. In the tislelizumab group, median OS for people whose cancer had PD-L1 levels equal to or above 1% was 27 months. For those whose cancer had less than 1% PD-L1, it was about 19 months.
• In contrast, ivonescimab was effective regardless of PD-L1 levels. In both the high and low PD-L1 groups, so many participants who had gotten ivonescimab were still alive that a median OS could not be calculated.

Serious health effects were similarly common in participants who got ivonescimab and those who got tislelizumab. They included:

• Reduced number of neutrophils in the blood (32% vs. 26%)
• Reduced number of white blood cells (11% vs. 9%)
• Low number of red blood cells (anaemia) (7% vs. 5%)

Bleeding occurred in about 3% of the ivonescimab group and about 1% of the tislelizumab group.

“This is the first large prospective trial to prove that an anti-PD-1/VEGF bispecific therapy plus chemotherapy is superior to the established standard of PD‑1 inhibitor plus chemotherapy in patients with advanced squamous lung cancer. While this study included participants from China and efficacy data from global populations are pending, it provides a vital new path forward for patients with these difficult-to-treat cancers who have limited treatment options,” said David R. Spigel, MD, FASCO, President and Chief Medical Officer at Sarah Cannon Research Institute and an ASCO Expert in lung cancer.

A separate study called HARMONi-3 is looking at the effects of ivonescimab in people with NSCLC in populations worldwide, including the U.S., Europe, and Asia.

Source: ASCO