A few months after Summit Therapeutics shocked the oncology world with an early claim that its lung cancer drug ivonescimab had beaten Merck’s Keytruda, it has backed up its talk with data.
In the Phase 3 results released Sunday at the World Conference on Lung Cancer in San Diego, the typical lung cancer patient treated with Summit’s drug went about 11.1 months before their cancer worsened, while the typical Keytruda-treated patient went 5.8 months. That added up to a 49% reduction in risk of progression or death for ivonescimab compared with Keytruda, the head-to-head study found.
“The results are striking and exceed the expectation of most clinical investigators,” John Heymach, chair of thoracic/head and neck medical oncology at MD Anderson Cancer Center, said in an interview with Endpoints News. Heymach was not involved in this study and is not a consultant to any of the involved drugmakers.
The study, called HARMONi-2, randomized 398 patients in China to receive either ivonescimab, bispecific antibody targeting PD-1 and VEGF, or Keytruda as their first treatment after diagnosis. The trial enrolled patients with PD-L1-positive, advanced non-small cell lung cancer.
Patients receiving Keytruda appeared to fare in line with previous studies of similar patients. The ivonescimab arm recorded a 5.3-month improvement in median progression-free survival — the study’s primary goal — compared with Keytruda.
“The findings from the HARMONi-2 study support the use of ivonescimab as a promising first-line treatment option for patients with PD-L1-positive advanced NSCLC,” Caicun Zhou, the principal investigator of the study, said in a statement.
Back in May, Summit announced topline results without specific data, just days before America’s biggest cancer conference kicked off in Chicago, describing the data at the time as historic and unprecedented. Sunday’s presentation appeared to back up those boasts.
Many combination therapies have tried and failed to beat Keytruda, Heymach added, which makes ivonescimab’s margin of success “striking and somewhat unexpected.” Keytruda has been the backbone of Merck’s business, helping usher in the age of immuno-oncology and along the way becoming one of the biggest-selling drugs of all time thanks to its breakthrough success treating difficult cancers.
Notably, Sunday’s presentation showed an edge over Keytruda both in patients expressing intermediate and high levels of PD-L1. Keytruda is most effective in the high-expressing population, less so in the intermediate population.
Ivonescimab’s data was “equally striking” for both groups, Heymach said.
A Pharmacylics repeat
The HARMONi-2 presentation brings Summit CEO Bob Duggan a step closer to championing another major cancer drug into existence. Duggan previously ran Pharmacyclics, selling it to AbbVie for $21 billion in 2015 based on the promise of its blood cancer drug Imbruvica.
Pharmacyclic’s success made Duggan a billionaire, and he’s attempting to repeat that playbook with Summit. He started buying shares of the company in 2018, becoming its largest shareholder and CEO by 2020. After Summit’s lead antibiotic drug failed in Phase 3, Summit paid $500 million upfront to the Chinese biopharma Akeso in December 2022 for commercial rights to ivonescimab in territories including the US and Europe.
Ivonescimab has made Summit one of the 2024’s best-performing biotech stocks, with its share price $SMMT up 365% year-to-date and the company commanding an $8.6 billion market capitalization.
It has also caught the attention of Baker Bros. Advisors, one of biotech’s top hedge funds, which last month disclosed a new position in Summit of 23.2 million shares.
Summit will still have to address some major questions before ivonescimab can become a reality in the US.
The study only enrolled patients in China, which raises questions both to its relevance to other populations as well as to previous concerns that FDA leaders have had with data packages relying on China.
“More work needs to be done before this can be applied to the Western population,” Heymach said.
The study also reported a higher rate of severe side effects for Summit’s drug than Keytruda. About 29% of patients who took Summit’s drug experienced treatment-related adverse events that were grade three or higher, compared with about 16% of the Keytruda arm. The biggest differences were too much protein in urine, hypertension, and laboratory abnormalities, according to Sunday’s presentation.
The study is still following patients for overall survival results, a key metric for cancer studies. Heymach said he expects the meaningful improvement in progression-free survival will translate, but the study will “need more time to see that data.”
Even with those caveats, Sunday’s reveal suggests Summit has a drug that could be a formidable foe to Keytruda.
“This is an extremely promising step for the drug, and if the finding is supported with studies of the Western population and the US, this could become the new standard treatment,” Heymach said.