Pfizer has announced topline results from the phase 3 SigVie-002 study (previously known as Be6A Lung-01) evaluating sigvotatug vedotin, an investigational, potential first-in-class integrin beta-6 (IB6) directed antibody-drug conjugate (ADC).
The study enrolled adults with locally advanced, unresectable or metastatic non-squamous non-small cell lung cancer (NSCLC) who had received one or more lines of prior therapy.
In the overall population, sigvotatug vedotin did not show a statistically significant improvement in the primary endpoint of overall survival (OS) compared to docetaxel. The safety profile of sigvotatug vedotin was manageable and consistent with prior studies.
Encouragingly, in patients who received only one prior line of systemic therapy, which represents two-thirds of the study population, a stronger trend was observed for OS and progression-free survival (PFS) for sigvotatug vedotin over docetaxel.
IB6 is associated with poor prognosis and, in NSCLC, IB6 is expressed on approximately 90% of tumours. Sigvotatug vedotin is a novel ADC designed for high target selectivity of IB6 and rapid internalisation, which may help limit binding to other integrins more likely to be expressed in normal tissues and potentially reduce off-target toxicity.
In the exploratory analysis, no clear IB6 expression-response relationship was observed. Detailed results from SigVie-002 will be submitted for presentation at a future medical congress.
“Patients with previously treated advanced NSCLC are a historically difficult-to-treat population, and there is clearly more work to be done to improve the outcomes for this population,” said Jeff Legos, Chief Oncology Officer, Pfizer.
“Although the overall study results did not demonstrate superiority over docetaxel, it is encouraging that second-line patients treated with sigvotatug vedotin achieved strong efficacy outcomes compared to an established standard of care, alongside a manageable safety profile.
“This observed clinical benefit, along with our phase 1 combination data in the first-line setting, reinforces our confidence in the potential of the sigvotatug vedotin programme, including an ongoing phase 3 trial in combination with pembrolizumab in first-line advanced NSCLC.”
Pfizer is evaluating sigvotatug vedotin in several ongoing studies across multiple stages and patient populations in NSCLC and other solid tumours.