New Lung Cancer Drug, Ivonescimab, Showed Promising Results In Major HARMONi-6 Trial, But U.S. Patients Will Need To Wait For HARMONi-3 Update

The results of the study were published in The Lancet, and despite HARMONi’s promise, patients in the U.S. must wait for additional data.

The results of HARMONi-6 will not change the current standard of care for patients with advanced squamous cell lung cancer because all patients enrolled in the trial were in China, and there are important differences in the patient population.

China-only trials have a track record of not always replicating well in Western populations, partly because of differences in tumor biology, patient genetics, smoking patterns, and how treatment is delivered. We’ve seen this play out before in lung cancer.

Because of this limitation, the findings will need to be confirmed in a global trial that includes U.S. patients, such as HARMONi-3, which is expected to report results soon.

Despite the caveats, experts SurvivorNet spoke to say the results are genuinely exciting and genuinely limited at the same time.

“What they demonstrated … was that people who got ivonescimab lived longer than people who got the tislelizumab [an immunotherapy]. I think it’s very exciting,” Dr. Deborah Doroshow, an oncologist at the Icahn School of Medicine at Mount Sinai in New York City, tells SurvivorNet.

What is Ivonescimab?

Ivonescimab is a bispecific antibody. Bispecific antibodies are designed to bind to two different targets at the same time — one on the cancer cell and one on an immune cell, usually a T cell, a powerful type of white blood cell responsible for killing abnormal cells.

Ivonescimab works differently from classic bispecific antibodies. The American Association for Cancer Research says that Ivonescimab simultaneously blocks two targets: PD-1, a protein on immune cells that cancer exploits to evade immune attack, and VEGF, a protein tumors use to grow new blood vessels. By hitting both pathways at once, the drug aims to restore the immune system’s ability to attack the cancer and cut off the tumor’s blood supply.

WATCH: How Do Biospecific Antibodies Work?

The patients in the trial had “untreated metastatic squamous lung cancer, which is one of the most difficult kinds of lung cancer to treat,” Dr. Doroshow explains.

Squamous cell lung cancer tends to affect older patients, often heavy smokers, and it doesn’t respond well to the targeted therapies that have transformed outcomes for other forms of lung cancer. For years, the main first-line or initial treatment approach for patients with advanced squamous disease has been chemotherapy combined with an immunotherapy drug, typically pembrolizumab (brand name Keytruda) in the United States.

It helps, but only to an extent. When a new drug like ivonescimab shows it can outperform the current standard in a randomized trial, the field pays attention as it signals it can become practice-changing.

Why is Ivonescimab Different?

Standard immunotherapy drugs like pembrolizumab work by blocking a protein called PD-1, which cancer cells use to hide from the immune system. Block that protein, and the immune system can recognize and attack the tumor. It works, but for many patients, it stops working or doesn’t work well enough to begin with.

Ivonescimab takes a different approach. It’s engineered to block two targets simultaneously: PD-1, like the drugs that already exist, and vascular endothelial growth factor (VEGF), a protein that tumors use to grow new blood vessels and sustain themselves. The idea is that hitting both pathways at once produces a stronger, more durable effect than either alone.

“All cancer cells need blood, just like we all need oxygen to breathe. And these medications can block the formation of new blood vessels to keep cancer cells alive,” Dr. Doroshow explains.

The question HARMONi-6 was designed to answer was whether combining both approaches into a single molecule would help patients live longer.

The data suggest it does, though how much and for whom is where it gets complicated.

What Did HARMONi-6 Find?

HARMONi-6 enrolled 532 patients with previously untreated advanced squamous lung cancer across China. Half received Ivonescimab plus chemotherapy. The other half received tislelizumab (a PD-1 immunotherapy drug similar to pembrolizumab that is approved in China) plus the same chemotherapy.

• At a follow-up of just under two years, patients on ivonescimab lived a median of 27.9 months. Patients on tislelizumab lived a median of 23.7 months. That’s a difference of roughly four months.
• At two years, 64.7% of patients on ivonescimab were still alive, compared to 48.6% of those on the comparison drug.

Those numbers are statistically significant and represent the first time a drug of this type (a bispecific antibody targeting both PD-1 and VEGF) has ever shown a survival benefit over a PD-1 inhibitor in a major randomized trial in any solid tumor.

While the average survival difference was about four months, the hazard ratio, which reflects the risk of dying over time, also favored ivonescimab, indicating a lower overall risk of death during the study.

Waiting for More Data to Better Understand Its Impact on American Patients

Dr. Doroshow highlights a major caveat for American patients, though. “This study was conducted entirely in China, where the drug was developed originally,” she explains.

Every single patient in HARMONi-6 was enrolled in China. The drug was tested against tislelizumab, not pembrolizumab, which is the drug American patients with squamous lung cancer are most likely already receiving. We know both drugs are effective PD-1 inhibitors, but they’re not identical, and comparing across trials is never as reliable as a direct head-to-head test.

There are also real biological and demographic differences between Chinese and American patient populations (tumor biology, smoking patterns, drug metabolism) that can affect both how well a treatment works and what side effects it causes.

“The FDA requires participants from all over the world to approve new medications, typically. And so right now the HARMONi-3 study is ongoing,” Dr. Doroshow explains. “It’s a very similar trial except it uses pembrolizumab instead of tislelizumab because that’s used more in the global context.”

HARMONi-3 is the trial that will answer the question American patients actually need answered: Does ivonescimab beat pembrolizumab (the current U.S. standard of care) in a global population that includes American patients? That trial is currently running. Results are expected in the second half of 2026.

Until those data sets arrive, Ivonescimab is not approved by the FDA. American patients cannot currently receive this drug outside of a clinical trial setting.

What This Means For Patients Now

If you’re a patient with advanced squamous cell lung cancer in the United States, the bottom line is that ivonescimab is not FDA-approved and is not available as a standard treatment here.

Pembrolizumab plus chemotherapy remains the standard first-line approach for most patients with advanced squamous NSCLC, unless you have a specific genetic mutation that calls for a targeted therapy. Your oncologist should test your tumor for genetic alterations before choosing a treatment plan.

WATCH: Molecular Testing: How Genetic Testing Shapes Lung Cancer Care

If you’re interested in ivonescimab, ask your doctor about clinical trials, specifically whether HARMONi-3 or any related study is enrolling patients at a center near you. That’s how American patients can currently access this drug and contribute to the data that will determine whether it eventually reaches U.S. practice.

“I think that study, HARMONi-3, will really be pivotal in terms of whether or not this drug gets approved by the FDA for the treatment of people with newly metastatic lung cancer,” Dr. Doroshow says.

The HARMONi-6 data are genuinely promising. The drug may well prove itself in the global trial and change practice here. But right now, the move is to make sure you’re on the best available treatment, that your tumor has been fully tested, and that you’ve had a real conversation with your oncologist about clinical trial eligibility, because that’s the path to ivonescimab if you want it.

Questions To Ask Your Doctor

• Has my tumor been tested for genetic mutations (including EGFR, ALK, RET, and others) that might change my treatment approach?
• Is pembrolizumab plus chemotherapy the right first-line treatment for me?
• Are there clinical trials involving ivonescimab or other novel immunotherapy combinations that I could be eligible for?
• What are the signs of VEGF-related side effects, and how would they be managed if I were on a drug like ivonescimab?
• Is HARMONi-3 enrolling at a cancer center near me?

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