Sigvotatug Vedotin Misses OS End Point in Phase 3 NSCLC Trial

Sigvotatug vedotin (SGN-B6A), an investigational antibody-drug conjugate (ADC) targeting integrin beta-6 (IB6), did not meet the primary end point of overall survival (OS) compared with docetaxel in the overall population of a phase 3 trial enrolling patients with previously treated nonsquamous non–small cell lung cancer (NSCLC).¹

The topline results come from SigVie-002 (NCT06012435), an open-label, randomized, global phase 3 study that enrolled 703 adults with locally advanced, unresectable, or metastatic nonsquamous NSCLC who had received at least 1 prior line of systemic therapy.

In a prespecified subgroup analysis, patients who had received only 1 prior line of systemic therapy (about two-thirds of the study population) showed a stronger trend toward improved OS and progression-free survival (PFS) with sigvotatug vedotin relative to docetaxel. An exploratory analysis found no clear relationship between IB6 expression level and treatment response.

“It is important not to underestimate the activity of docetaxel as a comparator in this setting. Patients enrolled in this trial were heavily pretreated, 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 [end point], 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,” said Solange Peters, MD, PhD, chair of the Medical Oncology and Thoracic Cancers Clinic, Lausanne University Hospital, Switzerland, in a news release. “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-naive patients with high PD-L1 expression warrant further evaluation and may represent a more effective clinical application of this strategy.”

Study Background and Rationale

SigVie-002 enrolled patients across 334 global sites. Patients were randomized to receive intravenous sigvotatug vedotin on days 1 and 15 of each 28-day cycle or intravenous docetaxel on day 1 of each 21-day cycle.² Secondary end points in the trial, assessed by blinded independent central review using RECIST v1.1 criteria, include PFS, confirmed objective response rate, duration of response, adverse event incidence, and quality of life. Those with actionable genomic alterations were eligible for participation; other inclusion criteria included an ECOG performance status of 0 or 1 and adequate hematologic, renal, and hepatic functions. The study excluded patients with active central nervous system metastases, uncontrolled diabetes mellitus, preexisting peripheral neuropathy ≥ grade 2, or evidence of select respiratory conditions, including noninfectious interstitial lung disease/pneumonitis.

The safety profile of sigvotatug vedotin was described as manageable and consistent with findings from earlier studies. Full results have not yet been published or peer-reviewed; detailed findings will be submitted for presentation at a future medical congress.¹

IB6 is expressed on approximately 90% of NSCLC tumors and has been associated with poor prognosis. Sigvotatug vedotin was designed for selective binding to IB6 with rapid internalization, an approach intended to limit cross-reactivity with other integrins expressed in normal tissue and reduce off-target toxicity.

REFERENCES

1. Pfizer Announces Topline Phase 3 Results for Sigvotatug Vedotin in Previously Treated Metastatic Non-Squamous Non-Small Cell Lung Cancer. News release. Pfizer Inc. June 22, 2026. Accessed June 23, 2026. https://tinyurl.com/w2cmt62j

2. A Study of SGN-B6A Versus Docetaxel in Previously Treated Non-small Cell Lung Cancer. ClinicalTrials.gov. Updated May 27, 2026. Accessed June 23, 2026. https://clinicaltrials.gov/study/NCT06012435