A New Type Of Immunotherapy Drug Showed Striking Results In Hard-to-Treat Lung Cancer, But More Data Is Needed For U.S. Patients

The data, simultaneously published in The Lancet, showed that patients who received ivonescimab lived for a median of 27.9 months versus 23.7 months for those who received standard immunotherapy, a 34% reduction in the risk of death.

SurvivorNet sat down with Dr. Pasi Jänne, Director of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute, at ASCO 2026 to discuss the results, which he calls “a game-changer.” However, the trial was conducted entirely in China, so the jury is still out on if these promising results will translate as well to patients in the U.S.

What Makes Ivonescimab Different

Standard immunotherapy drugs for lung cancer, like pembrolizumab (brand name Keytruda), the most widely used, work by blocking a single protein called PD-1, which cancer cells exploit to hide from the immune system. Remove that shield, and the immune system can attack the tumor.

Ivonescimab does something more ambitious. It’s a bispecific antibody, meaning it’s engineered to hit two targets at once. It blocks PD-1, like the drugs that came before it, but it also blocks a protein called VEGF, which tumors use to grow new blood vessels and create a hostile environment that blunts immune responses.

“I think it’s the cooperative binding that happens when the two are together, where you don’t get that at each individual level,” Dr. Jänne explains. “And certainly we’re starting to see that in the results from the clinical trials, so I think that speaks volumes about this new approach.”

Until now, drugs targeting VEGF have been considered too dangerous in the squamous NSCLC setting. Squamous tumors often sit near major blood vessels, and anti-VEGF therapy can cause life-threatening bleeding. Ivonescimab appears to achieve VEGF blockade through a different mechanism that may be safer, though the bleeding risk is not zero and requires monitoring.

What HARMONi-6 Found

The HARMONi-6 trial enrolled 532 patients with previously untreated advanced squamous NSCLC at 50 centers across China. Patients were randomly assigned to receive either ivonescimab plus platinum-based chemotherapy, or tislelizumab (another PD-1 inhibitor) plus the same chemotherapy.

Earlier results presented at the European Society for Medical Oncology (ESMO) Congress in October 2025 and published simultaneously in The Lancet showed that patients receiving ivonescimab lived significantly longer without their cancer progressing — about 11 months on average, compared to roughly 7 months for those on the other drug. That’s a 40% reduction in the risk of progression or death

That benefit was consistent regardless of whether patients’ tumors expressed high or low levels of PD-L1, a protein often used to predict who will respond to immunotherapy.

The ASCO presentation added how long patients actually lived:

• Patients on ivonescimab lived a median of 27.9 months, nearly two and a half years. Patients on tislelizumab lived a median of 23.7 months.
• That’s a meaningful difference of about four months, and it translated to a 34% lower risk of dying at any given point during the study.
• Two years into the trial, nearly 65% of patients on ivonescimab were still alive, compared to less than 49% of those on the comparison drug.

Ivonescimab did cause more side effects than the comparison drug, but that’s not surprising when you’re targeting two pathways instead of one.

“When you have two drugs in one, you can also get additional side effects from those two drugs,” Dr. Jänne explains. “We want to see what is the additional cost in terms of side effects, and are those tolerable and manageable side effects.”

In practice, most of the additional side effects with ivonescimab showed up in blood tests, like changes in blood cell counts, rather than as symptoms patients could feel. Only 5% of patients in both groups had to stop treatment because of side effects, which is reassuring.

The one side effect that requires specific attention is bleeding. About 3% of patients on ivonescimab experienced a serious bleeding event, compared to 1% of those on the comparison drug. That risk was higher in patients whose tumors were located near major blood vessels or who had a history of coughing up blood, so screening for those risk factors before starting treatment is important.

Limitations: Trial Was Conducted Only in China

The HARMONi-6 trial was conducted entirely in China. The study included only Chinese patients up to age 75 and very few women were enrolled, since squamous lung cancer overwhelmingly affects male smokers in China. That means the results may not translate perfectly to a more diverse U.S. patient population, where tumor biology, genetics, and smoking history can differ.

There’s also a comparison problem that’s worth understanding. Ivonescimab was tested against tislelizumab, a drug that is approved in the U.S. but is not the standard of care here. American patients with squamous lung cancer are most likely to be treated with pembrolizumab (Keytruda), which is a different drug.

We don’t yet know how ivonescimab compares to pembrolizumab.

“This is a Chinese only study. We are seeing more of these studies in the U.S. as well now, and I think it’s important to get data on both or worldwide populations, as there are medicines that can be metabolized differently in different ethnic groups, which may impact both side effects and efficacy,” Dr. Jänne explains.

That global comparison is coming. A separate trial called HARMONi-3 is currently running globally and does compare ivonescimab to pembrolizumab plus chemotherapy. Final data from the squamous cohort of HARMONi-3 are expected in the second half of 2026.

Until those results arrive, the HARMONi-6 data are scientifically important and genuinely exciting, but they don’t yet mean that ivonescimab is available or the new standard of care for American patients.

What This Means For Patients Now

Ivonescimab is not yet approved by the Food and Drug Administration (FDA) for any indication in the United States.

If you or someone you love has been diagnosed with advanced squamous non-small cell lung cancer, the standard first-line treatment in the U.S. currently involves chemotherapy combined with pembrolizumab, unless there are specific genetic mutations that call for a different approach. Your oncologist should test your tumor for relevant mutations, including EGFR, ALK, and others, before choosing a treatment plan.

“The study was done in newly diagnosed patients with advanced squamous cell lung cancer. So if you go by the study, that’s the indication where it would be appropriate,” Dr. Jänne adds about who this approach is for. “It’s important for patients to understand that not all positive trials mean that the medicine can be used at any point during the course of treatment.”

If you’ve already received treatment and are now looking at next steps, this particular study doesn’t apply to you, though other trials may.

If you’re interested in ivonescimab, clinical trials are currently the path. HARMONi-3 is enrolling patients globally, including in the United States. Ask your oncologist whether you might be eligible.

Right now, the trial results represent a significant step forward, Dr. Jänne says.

“It’s really the first randomized trial to show a benefit of this drug over chemotherapy-immunotherapy alone in squamous cell cancer specifically,” he adds. “I think it’s, I hope, a bit of an inflection point that we’ll continue to see more after this — but it’s a significant finding for the field.”

The question of whether that significance translates directly to American patients will be answered by HARMONi-3.

Questions To Ask Your Doctor

• What type of lung cancer do I have, and has my tumor been tested for genetic mutations?
• What is my PD-L1 expression level, and how does that affect my treatment options?
• Is pembrolizumab plus chemotherapy the right first-line approach for me?
• Are there clinical trials involving ivonescimab or other novel immunotherapy combinations that I should consider?
• What is the risk of bleeding with anti-VEGF-based therapies given my tumor’s location?

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