A double-barreled cancer immunotherapy extended the lives of people with lung cancer in a closely watched trial that’s viewed as important for gauging the potential impact of the drug, known as ivonescimab, as well as others like it. 

Presented at the American Society of Clinical Oncology meeting Sunday, the findings come from a study testing ivonescimab in patients newly diagnosed with advanced, non-small cell lung cancer. Though run only in China, the study is a proxy for a global trial that could be worth tens of billions of dollars to the drug’s developers, Akeso and Summit Therapeutics. Like that global study, the China trial is testing an ivonescimab-chemotherapy combination against the kind of immunotherapy-chemo regimen that’s standard care for many new patients. 

Last year, Akeso and Summit revealed that the ivonescimab regimen reduced the risk of disease progression by 40% when compared to chemo and an immunotherapy called Tevimbra. But they hadn’t yet disclosed whether the drug regimen extended lives, the gold standard for a cancer medicine. 

Success in that objective carries implications not only for Akeso and Summit, but many others developing medicines like ivonescimab, which are known as “PD-1/VEGF inhibitors” because of the two proteins they target. These drugs have shown the potential to top widely used immunotherapies like Keytruda, sparking hope that they may become future cornerstones of cancer care. But modest results in some studies have stirred debate about their additive benefits.

Heading into the ASCO presentation, multiple Wall Street analysts pegged a reduction in death risk of anywhere from 20% to 30% as indicative of a meaningful benefit. Ivonescimab hit that mark, with investigators disclosing Sunday that drug recipients lived a median of 28 months after enrollment, versus 24 months for the control group — a 34% relative risk reduction that was statistically significant. 

Both drug combinations had similar side effects, such as lower counts of red and white blood cells, though the rates of those events were slightly higher among ivonescimab recipients. 

“The demonstration of both improved progression-free survival by a substantial margin, as well as a significant overall survival [benefit], is a real step forward because it comes at the cost of very little additional toxicity,” said John Heymach, chair of thoracic and head and neck cancer care at MD Anderson Cancer Center, in an interview. 

Heymach, who isn’t involved in the Harmoni-6 trial but is an investigator in another ivonescimab study, noted that the medicine’s safety profile could set it apart from certain antibody-drug conjugates that are also being tested in lung cancer. Those drugs tend to have higher side effect rates, which could limit their use among some people, he said. 

The four-month absolute difference in survival observed in the study appears to have fallen short of investor expectations. Analysts at the investment bank Cantor Fitzgerald, for instance, had predicted that a six-month benefit would be viewed as clinically meaningful.

Still, ahead of the meeting there were warning signs ivonescimab might not hit that mark. Analysts at a different firm, Leerink Partners, noted in how the survival numbers in the study might be skewed by inconsistent access to quality care in China.

Whether that impacted the findings is unclear. But one oncologist not involved in the study argued that the magnitude of the effects Akeso and Summit found were notable nonetheless.

“A few months may not seem like a lot of time for patients who already have very limited options,” but it does add to what becomes a “cumulative benefit” over time, said Lee Hong, a thoracic oncologist with City of Hope. Extending survival with an initial medication “just opens up many doors for for these patients, even [when] thinking about subsequent lines of therapy,” Hong said.

Ivonescimab is approved for use in China and currently under review in the U.S. as a potential treatment for certain EGFR-mutated lung cancers, with a decision expected in November. But its biggest opportunity lay ahead, if that all-important global study testing ivonescimab and chemo against chemo and Merck & Co.’s Keytruda — the primary treatment for many lung tumors — yields positive results.

Unlike the China trial, the global study, HARMONi-3, includes people with “non-squamous” disease. That difference could boost ivonescimab’s chances, as “squamous” disease tends to be more difficult to treat.

A final analysis from HARMONi-3 is expected later this year.