Pfizer announced topline results from the Phase 3 SigVie-002 study evaluating sigvotatug vedotin, an investigational, potential first-in-class integrin beta-6-directed antibody-drug conjugate.
The study enrolled adults with locally advanced, unresectable, or metastatic non-squamous non-small cell lung cancer who had received one or more prior lines of therapy.
In the overall study population, sigvotatug vedotin did not show a statistically significant improvement in the primary endpoint of overall survival compared to docetaxel. Pfizer said the safety profile of sigvotatug vedotin was manageable and consistent with prior studies.
The company also said that patients who had received only one prior line of systemic therapy, representing about two-thirds of the study population, showed a stronger trend for overall survival and progression-free survival with sigvotatug vedotin compared to docetaxel.
In an exploratory analysis, Pfizer reported no clear integrin beta-6 expression-response relationship. Detailed results from the SigVie-002 study will be submitted for presentation at a future medical congress.
Sigvotatug vedotin is designed to target integrin beta-6, which Pfizer said is expressed on approximately 90% of non-small cell lung cancer tumors and is associated with poor prognosis. The investigational antibody-drug conjugate is designed for high target selectivity and rapid internalization, which may help limit binding to other integrins more likely to be expressed in normal tissues and potentially reduce off-target toxicity.
Pfizer is continuing to evaluate sigvotatug vedotin across several ongoing studies in non-small cell lung cancer and other solid tumors. This includes an ongoing Phase 3 study evaluating sigvotatug vedotin in combination with pembrolizumab in first-line non-small cell lung cancer with PD-L1 tumor proportion score of at least 50%.
The company is also exploring sigvotatug vedotin in novel combinations, including with PF-08634404, Pfizer’s investigational bispecific antibody targeting PD-1 and VEGF, in early-stage lung cancers and other integrin beta-6-expressing tumors.
Since acquiring Seagen, Pfizer has continued to advance a broad antibody-drug conjugate portfolio spanning marketed medicines and pipeline programs. The company is also progressing fetrastobart vedotin, a PD-L1-directed antibody-drug conjugate currently in Phase 3 development in non-small cell lung cancer, along with additional integrin beta-6-targeted antibody-drug conjugates and early-stage candidates involving novel targets and payloads.
The SigVie-002 trial is an ongoing, open-label, randomized Phase 3 global study comparing sigvotatug vedotin with docetaxel in adults with previously treated locally advanced, unresectable, or metastatic non-small cell lung cancer. The study enrolled 703 participants.
KEY QUOTES:
“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.”
“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 program, including an ongoing Phase 3 trial in combination with pembrolizumab in first-line advanced NSCLC.”
Jeff Legos, Chief Oncology Officer of Pfizer
“It is important not to underestimate the activity of docetaxel as a comparator in this setting. Patients enrolled in this trial were heavily pre-treated, with most having previously received both platinum-based chemotherapy and immunotherapy, yet docetaxel continues to provide meaningful clinical benefit.”
“Although the study did not meet its overall survival endpoint, in second-line patients the data suggest a clinically meaningful survival benefit for sigvotatug vedotin over docetaxel, supporting continued scientific evaluation of sigvotatug vedotin in earlier lines in combination with immunotherapy.”
“The ability of sigvotatug vedotin to induce immunogenic cell death provides a strong rationale for combination approaches with immunotherapy, particularly in earlier treatment settings where immune competence is better preserved. In this context, the promising phase 1 efficacy signals observed in treatment-naïve patients with high PD-L1 expression warrant further evaluation and may represent a more effective clinical application of this strategy.”
Solange Peters, M.D., PhD, Chair of Medical Oncology & Thoracic Cancers Clinic at Lausanne University Hospital
