Pfizer's Sigvotatug Vedotin Misses Overall Survival Goal in Phase 3 Lung Cancer Trial

Pfizer said on June 22 that its investigational antibody-drug conjugate (ADC) sigvotatug vedotin did not show a statistically significant improvement in overall survival, the primary endpoint, compared with docetaxel chemotherapy in the Phase 3 SigVie-002 trial in previously treated non-squamous non-small cell lung cancer (NSCLC), according to the company's topline release. The results are company-reported topline data; Pfizer did not disclose hazard ratios or median survival figures and said detailed results will be submitted to a future medical congress.

The trial and the subgroup

SigVie-002 (NCT06012435), previously known as Be6A Lung-01, is an open-label, randomized, global study that enrolled 703 adults with locally advanced, unresectable or metastatic non-squamous NSCLC who had received at least one prior line of therapy. Patients received intravenous sigvotatug vedotin on days 1 and 15 of each 28-day cycle or docetaxel on day 1 of each 21-day cycle. The trial ran at 334 sites, Targeted Oncology reported.

Pfizer said that in patients who had received only one prior line of systemic therapy, about two-thirds of the study population, a stronger trend was observed for overall survival and progression-free survival with sigvotatug vedotin over docetaxel. Targeted Oncology described this as a prespecified subgroup analysis. An exploratory analysis found no clear relationship between tumor IB6 expression and response. Pfizer said the safety profile was manageable and consistent with prior studies.

"It is important not to underestimate the activity of docetaxel as a comparator in this setting," said Solange Peters, chair of the Medical Oncology and Thoracic Cancers Clinic at Lausanne University Hospital, in Pfizer's release. She said most patients had previously received both platinum-based chemotherapy and immunotherapy.

The drug and what comes next

Sigvotatug vedotin targets integrin beta-6 (IB6), which Pfizer says is expressed on about 90% of NSCLC tumors and is associated with poor prognosis. The company described it as a potential first-in-class ADC designed for high selectivity for IB6. Pfizer said it has continued to advance a broad ADC portfolio since its acquisition of Seagen.

Pfizer said it continues a Phase 3 study of sigvotatug vedotin with pembrolizumab in first-line NSCLC with a PD-L1 tumor proportion score of at least 50%, and is exploring combinations including PF-08634404, its investigational PD-1 and VEGF bispecific antibody. Peters said Phase 1 signals in previously untreated patients with high PD-L1 expression warrant further evaluation.