Summit lung cancer drug shows ‘striking’ benefit over Keytruda
An experimental medicine from a small biotechnology company cut the risk of lung cancer progression in half when tested against the world’s most dominant immunotherapy in a clinical trial, according to study data presented Sunday at a major medical meeting.
The results come from a Phase 3 trial pitting a drug from biotech Summit Therapeutics against Merck & Co.’s Keytruda in people recently diagnosed with advanced non-small cell lung cancer.
Data show Summit’s drug held tumors at bay for a median of just over 11 months, compared to almost six months for those given Keytruda. The 5.3-month difference in progression-free survival equated to a statistically significant 49% reduction in the risk of cancer progression or death.
“It's not always that we see a drug improving median progression-free survival by almost six months,” said Gilberto Lopes, chief of medical oncology at the University of Miami’s Sylvester Comprehensive Cancer Center. “I have no doubt that this is a positive study.”
Summit’s full findings have been eagerly anticipated since May, when the company claimed, without details, that its drug “decisively” beat Keytruda. According to Summit, no other medicine has outperformed Keytruda in a late-stage lung cancer study — one reason why Merck’s therapy has become one of the most lucrative pharmaceutical products in the decade since its initial U.S. approval.
Should further testing show a similar benefit, Summit’s drug, which is known as ivonescimab, has a chance to become a “new standard” over Keytruda for treating these patients, said John Heymach, chair of thoracic, head and neck oncology at the MD Anderson Cancer Center.
The data are “really quite striking,” according to Heymach, who discussed the trial results after their presentation Sunday at the World Conference on Lung Cancer in San Diego. “The fact that there’s such a difference between these two immunotherapies is quite notable, particularly because it doesn’t come with new, or unexpected, toxicity,” he said.
Still, Summit’s findings come with important limitations. The study didn’t test ivonescimab against the Keytruda and chemotherapy combination that’s now standard treatment for most non-small cell lung cancer cases. It was also run only in China, making a Food and Drug Administration approval unlikely and raising questions about how generalizable the results may be in a more diverse population.
“Even though this result shows ivonescimab is better than Keytruda in this setting — at least for progression-free survival — we truly don’t know if it’s better than Keytruda plus chemo,” said Lopes.
Discovered by the China-based biotech Akeso, ivonescimab works differently than Keytruda, which blocks the immune-regulating protein PD-1. Rather, it simultaneously stifles PD-1 and another target implicated in tumor growth, called VEGF. While there are other cancer medicines that inhibit VEGF, obstructing both pathways with a single therapy might have enhanced effects, doctors told BioPharma Dive.
For its study, Summit enrolled 398 people with previously untreated non-small cell lung cancer whose tumors expressed an important protein in at least 1% of malignant cells. This protein, PD-L1, interacts with PD-1 to shield tumors from the immune system.
Participants were randomized into roughly equal-sized groups and given either Keytruda or ivonescimab once every three weeks, with treatment continuing until either benefits waned or “unacceptable” side effects occurred. The study sought to show ivonescimab delays tumor progression, with overall survival a secondary assessment.
In addition to the headline finding, investigators observed a roughly 50% risk reduction in participants who had low levels of PD-L1 as well as in those with high levels. The benefit of Summit’s drug was also similar in people with squamous or non-squamous forms of lung cancer. Treatment shrank tumors in a greater percentage of study volunteers than did Keytruda.
The data appear to surpass expectations analysts held going into the meeting. In July, Bradley Canino of the investment bank Stifel noted how a 40% or better overall risk reduction would be an “ideal outcome.” Jefferies’ Akash Tewari last month speculated Summit’s drug would delay tumor progression by about 10 months, a bar it cleared.
Yet several doctors noted how they want to see ivonescimab compared to Keytruda and chemo, particularly for patients whose tumors express low levels of PD-L1 and for whom the combination’s use is standard. Given how embedded Keytruda is in lung cancer treatment, Summit might also need to prove its therapy keeps people alive longer to convince doctors to change their treatment plans.
“I would want to see overall survival data and the magnitude of that difference, to see if it were something that would be meaningfully important to put into practice,” said Richard Hall, a medical oncologist at the University of Virginia.
Treatment-related side effects judged as “serious” by trial monitors occurred in about 21% of participants who received Summit’s drug versus 16% of those given Keytruda. Overall, side effects classified as Grade 3 or worse — including those not attributed to treatment — occurred in about 29% of people on ivonescimab compared to roughly 16% on Keytruda.
High blood pressure and excessive protein in the urine, an indication of kidney stress, were more common in people who got Summit’s drug, as were elevations in liver enzymes.
Jyoti Malhotra, director of thoracic medical oncology at City of Hope Orange County, said hypertension and proteinuria are common side effects with VEGF inhibitors. Typically, they’re managed by withholding the VEGF-blocking part of combination drug regimens until symptoms clear.
“But here it's one drug combined together,” said Malhotra. “If we see [concerning] proteinuria, then we’d have to withhold the whole drug.”
Summit has already begun a global study that could answer some of the questions Sunday’s data raise. The multicountry trial is testing Summit’s drug and chemotherapy against Keytruda and chemo. Results from that study are expected in 2027, according to a federal database. And on Sunday, the company announced plans for another study comparing ivonescimab to Keytruda in lung cancer patients with high PD-L1 levels.
Already, ivonescimab’s success has given Summit, a 21-year-old biotech, a major boost. The company has shifted strategies multiple times, moving on from a muscular dystrophy medicine and later an antibiotic that both failed clinical trials. But oncology has become its focus under Robert Duggan, who last decade sold his previous company, Pharmacyclics, to AbbVie for $21 billion.
“We believe this is the beginning of a landscape shift for treatment options for patients living with cancer,” said Duggan, in Summit’s Sunday statement.
Jonathan Gardner and Ned Pagliarulo contributed reporting.
Editor’s note: This story has been updated with additional detail from Summit.
This story was originally published on BioPharma Dive. To receive daily news and insights, subscribe to our free daily BioPharma Dive newsletter.
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