Summit Akeso ivonescimab improves survival in Harmoni-6 trial

An experimental lung cancer drug from Akeso and Summit Therapies It reduced the risk of death by 34% in a closely monitored late-stage trial, according to results released Sunday.

When combined with chemotherapy, the drug kept people with non-small cell squamous lung cancer alive an average of four months longer than the standard combination of immunotherapy and chemotherapy; This was a statistically significant result, according to an abstract published Sunday at the annual meeting of the American Society of Clinical Oncology. The Phase 3 trial was conducted in China and the global Phase 3 study is ongoing.

Dr., executive director of Emory University Winship Cancer Institute. “The fact that it showed an improvement in overall survival in a difficult-to-treat patient population is very encouraging,” said Suresh Ramalingam, MD. “I am aware of the fact that this trial was conducted only in China, and this raises the question of how to apply these data to patient populations outside of China, which will require future research.”

The bispecific antibody, called ivonescimab, targets PD-1, similar to Merck’s best-selling drug Keytruda, and VEGF, similar to Roche’s Avastin. It has become the subject of intense debate in the oncology and investment communities. While some say ivonescimab and similar drugs could be successors to Merck’s highly successful cancer drug Keytruda, others warn that it will disappoint like other once-promising ideas, such as drugs targeting TIGIT, an immune receptor.

The dueling stories are also reflected in the share prices of US-based Summit Therapeutics, which licensed the rights to ivonescimab outside China from Akeso. Summit’s shares have risen nearly 600% in the two years since Summit said ivonescimab controlled tumors more effectively than Keytruda in a separate Chinese trial. The stock fell last month due to concerns that the drug would not be as effective in the global population.

Previous studies have shown that ivonescimab can effectively control tumors, an endpoint known as progression-free survival. That’s usually not enough to win approval from the U.S. Food and Drug Administration, which wants evidence that cancer drugs can keep people alive longer. Older VEGF drugs that effectively control tumors have struggled to improve survival, raising doubts that ivonescimab’s early promises will hold.

In the Harmoni-6 trial presented Sunday, ivonescimab combined with chemotherapy kept people alive for an average of 27.9 months, compared with 23.7 months for people receiving the PD-1 drug and chemotherapy alone; This means a four-month recovery.

D., professor of medicine, hematology and medical oncology at the Icahn School of Medicine at Mount Sinai. “It’s not clear how significant this is,” said Deborah Doroshow. “It’s definitely not two months, but it’s also not a huge difference, and I think whether it makes sense to live four months longer definitely depends on the person living it.”

Doroshow, who serves on the steering committee for the ongoing Harmoni-3 global ivonescimab trial, said people who received immunotherapy in the control group lived an average of six months longer than expected, raising questions about whether the trial was enrolling a representative patient population and whether ivonescimab’s advantage was better than reported in the study.

One possible reason for the discrepancy is that the study was conducted in China, where people have historically responded better to standalone PD-1 and VEGF drugs, Emory’s Ramalingam said. The only way to determine whether combining the two in one molecule produces different results for broader populations is to conduct additional studies in the West, he said.

Until then, Ramalingam called the trial results “good news” for Chinese patients.

“There is a new approach that extends survival in squamous cell lung cancer by approximately four months, which is a significant advance given that this is a patient population where progress occurs in small steps,” he said.

Summit plans to report progression-free survival results from squamous patients in the global Harmoni-3 trial in the second half of this year. It expects to share results for non-squamous patients in the first half of next year.

One of the purported benefits of drugs targeting PD-1/VEGF is the ability to safely deliver them to people with squamous lung cancer, a subgroup most commonly caused by smoking. These tumors tend to arise near large blood vessels in the lungs, and blocking VEGF can prevent these blood vessels from repairing themselves, leading to potentially fatal bleeding.

In the trial presented Sunday, nearly a quarter of people in the ivonescimab group experienced bleeding of any severity, twice as many as in the control group. Less than 3% of cases were considered serious, while about 1% of people taking the PD-1 drug tislelizumab were considered serious, according to slides to be presented Sunday, in which the presenter described the safety of ivonescimab as comparable.

More generally, drugmakers and investors want to know whether PD-1/VEGF drugs will replace similar drugs such as Keytruda and Bristol Myers Squibb’s Opdivo as primary treatment. Checkpoint inhibitors like Keytruda have revolutionized the treatment of lung cancer and are now used in dozens of other cancers. Keytruda alone has 44 indications and generated more than $30 billion in sales for Merck last year.

Leerink Partners analyst Daina Graybosch said replacing Keytruda wherever it is used today and potentially expanding it into new indications would create a “very large market.” This expectation led to a rush to make deals.

Licensing deals involving PD-1 drugs reached $30 billion last year; It has nearly doubled its previous peak of $16 billion in 2017, a few years after Keytruda and Opdivo reached the market. Merck and Bristol Myers Squibb were part of the recent foray, with both companies signing potentially multibillion-dollar deals for PD-1/VEGF drugs.

But Ethan Smith, Norstella’s director of oncology, said ivonescimab and similar drugs are unlikely to become so widely used, especially as they face more competition from other emerging drugs such as antibody drug conjugates, which Keytruda had when it entered the market more than a decade ago.

Data from an antibody drug conjugate Merck and its partner Kelun It will also be presented at the ASCO meeting this weekend. In a Chinese study on lung cancer, the experimental drug reduced the risk of tumor progression by 65%, according to an abstract released before the meeting.

Merck’s global head of oncology clinical development, Dr. Marjorie Green said that although Merck thinks there will be room for PD-1/VEGF drugs and is excited about the drug it is developing, the company does not expect them to be the next Keytruda.

“It’s an exciting time in oncology,” Green said. “I never thought we’d be in a position to debate which of the new treatments is best for lung cancer because there hasn’t been a lot of progress. Keytruda has just become a baseline therapy, and people are asking, ‘What’s going to replace it?’ they think. “And I think it’s good news for people who are unfortunately diagnosed with lung cancer that we’re in a position to say: There may be a lot of options that we can do, and then hopefully we can put them together and help even more.”