Phase 3 Data Supports Biotech's Claims of Outperforming Keytruda in Lung Cancer

A few months after Summit Therapeutics made headlines in the oncology community with preliminary claims that its lung cancer drug ivonescimab outperformed Merck’s Keytruda, the company has now presented more detailed data to substantiate those claims. At the World Conference on Lung Cancer in San Diego, Phase 3 results were shared, showing that typical lung cancer patients treated with ivonescimab experienced a progression-free period of about 11.1 months, compared to 5.8 months for those treated with Keytruda. This equates to a 49% reduction in the risk of cancer progression or death for patients on ivonescimab.

John Heymach, chair of thoracic and head and neck medical oncology at MD Anderson Cancer Center, commented on the results, describing them as striking and exceeding the expectations of most clinical investigators. Although Heymach did not participate in the study and does not consult for any involved drug manufacturers, his perspective emphasizes the significance of the findings.

The trial, named HARMONi-2, involved 398 patients in China, who were randomly assigned to receive either ivonescimab—a bispecific antibody targeting PD-1 and VEGF—or Keytruda as their initial treatment after diagnosis. The study focused on patients with PD-L1-positive, advanced non-small cell lung cancer. Patients in the Keytruda arm showed results consistent with previous studies, while those in the ivonescimab arm demonstrated a median progression-free survival improvement of 5.3 months compared to Keytruda.

Caicun Zhou, the principal investigator of the study, highlighted that the HARMONi-2 findings support ivonescimab as a promising first-line treatment for patients with PD-L1-positive advanced non-small cell lung cancer (NSCLC). Earlier in May, Summit had announced topline results without specific data, labeling the results as historic and unprecedented. The recent presentation appears to validate those statements.

Heymach noted the success of ivonescimab as particularly notable given the numerous combination therapies that have previously failed to surpass Keytruda. Keytruda has been a cornerstone of Merck’s portfolio, playing a pivotal role in the era of immuno-oncology and becoming one of the best-selling drugs due to its effectiveness in treating various hard-to-treat cancers.

Interestingly, the presentation showed ivonescimab's advantage over Keytruda in patients with both intermediate and high levels of PD-L1 expression. While Keytruda is most effective in high-expressing populations, it is less so in intermediate populations. Ivonescimab demonstrated similarly striking data for both groups.

Summit CEO Bob Duggan, who previously led Pharmacyclics and sold it to AbbVie for $21 billion thanks to its blood cancer drug Imbruvica, is now closer to bringing another major cancer drug to market. Duggan became Summit’s largest shareholder and CEO by 2020, following the failure of Summit’s lead antibiotic drug in Phase 3 trials. Summit acquired commercial rights to ivonescimab from the Chinese biopharma company Akeso for $500 million in December 2022. Since then, ivonescimab has significantly boosted Summit's stock performance, making it one of the best-performing biotech stocks of 2024, with a market capitalization of $8.6 billion.

However, Summit faces several challenges before ivonescimab can be approved in the US. The study's exclusive enrollment of patients in China raises questions about its applicability to other populations and concerns about FDA approval based on data predominantly from China. Heymach emphasized that more work is needed to validate these findings for Western populations.

The study also reported a higher incidence of severe side effects for ivonescimab compared to Keytruda. Around 29% of patients on ivonescimab experienced grade three or higher treatment-related adverse events, compared to 16% in the Keytruda arm. Notable side effects included excessive protein in urine, hypertension, and laboratory abnormalities.

The trial is ongoing, with patients still being monitored for overall survival outcomes—a critical metric for cancer therapies. While Heymach is optimistic that the improvement in progression-free survival will translate into better overall survival, he acknowledges that more time is needed to confirm these results. Despite these challenges, the data suggests that ivonescimab could become a formidable competitor to Keytruda, potentially setting a new standard for treatment if further studies validate these findings in broader populations.

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