Pfizer lung-cancer drug sigvotatug vedotin falls short in closely watched trial
Pfizer on Monday released phase 3 results for its antibody-drug conjugate (ADC) sigvotatug vedotin in non-small-cell lung cancer (NSCLC). The company said the trial had missed its primary survival endpoint, a serious setback for one of the most closely watched oncology readouts in months.
The trial pitted sigvotatug vedotin against current standard-of-care chemotherapy in patients with advanced NSCLC who had already been treated with immunotherapy and platinum chemotherapy. Analysts speaking to STAT News said they had been expecting positive signals on both overall and progression-free survival, but the data fell short of statistical significance.
ADCs combine an antibody that recognises a specific target on a cancer cell's surface with a potent chemotherapy payload. Sigvotatug vedotin targets B7-H4, a protein frequently expressed in lung cancers. Pfizer has been building out its ADC platform after its $43 billion acquisition of Seagen; this asset was one of the headline expectations of that deal.
Pfizer's head of oncology said in a statement that «the results fell below our expectations; we are evaluating the full dataset and examining subgroups in detail». The company said it would discuss the regulatory path with the US Food and Drug Administration once more analyses are complete.
The Wall Street reaction was sharp: Pfizer shares fell almost 4 per cent in Monday trading. Investors had been counting on sigvotatug vedotin as part of the bridge to revenue after the loss of exclusivity on Keytruda exposes the broader oncology market. Similar ADC candidates from Bristol-Myers Squibb and Daiichi Sankyo are also being watched closely.
Non-small-cell lung cancer is the leading cause of cancer death worldwide. In Turkey, about 40,000 new lung-cancer cases are diagnosed each year, the vast majority of them NSCLC. Because many patients are diagnosed at an advanced stage, second- and third-line treatment options are critical.
Dr Charles Rudin, an oncologist at Memorial Sloan Kettering, told STAT News that «the concept of a B7-H4-directed ADC was promising, but the complexity of the lung microenvironment makes it the hardest battlefield for the ADC class». Rudin added that, once subgroup data are published, a role may still emerge in patients with certain mutations.
The ADC class has produced significant wins over the last five years in breast, bladder and gastric cancers. Enhertu, from the AstraZeneca-Daiichi partnership, has dramatically extended survival in HER2-positive tumours. But the class's record in lung cancer is mixed: candidate drugs from Merck and Gilead suffered similar setbacks last year.
Pfizer said another phase 3 readout for sigvotatug vedotin is scheduled for late 2026 and that the development programme will continue. The company is also pursuing combination studies of the drug in gynaecological cancers.
The FDA's most recent NSCLC ADC approval went to AstraZeneca-Daiichi's datopotamab deruxtecan last year, but the label was restricted to a narrow subgroup. Pfizer's result today is another sign that the door to lung cancer remains hard to open for the ADC class.
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