sigvotatug vedotin

Shows activity

Also known as:

SGN-B6A

Cancer types include:

bladder cancer breast cancer cervical cancer esophageal cancer head and neck cancer

TrialFetch AI Analysis

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Overview

Sigvotatug vedotin (SGN-B6A) is an investigational antibody–drug conjugate (ADC) targeting integrin beta-6 (IB6/ITGB6), a cell-surface adhesion protein expressed at low levels in most healthy tissues but frequently overexpressed in solid tumors. Clinical development has focused primarily on non-small cell lung cancer (NSCLC), with additional early-phase cohorts in head and neck and esophageal cancers. (ascopubs.org)

Mechanism of action

The ADC consists of an IB6-selective monoclonal antibody linked through a protease-cleavable maleimidocaproyl–valine-citrulline linker to monomethyl auristatin E (MMAE). After IB6 binding and internalization, MMAE is released and disrupts microtubules, causing cell-cycle arrest and apoptosis. Preclinical studies also indicate bystander killing and induction of immunogenic cell death, providing a rationale for combinations with immune-checkpoint inhibitors. (pfizeroncologydevelopment.com)

Efficacy

In a peer-reviewed phase I analysis of 117 previously treated patients with advanced NSCLC, sigvotatug vedotin monotherapy produced:

Objective response rate (ORR): 19% (95% CI, 12%–27%), including three complete responses
Median duration of response: 11.3 months
Disease-control rate: 68%
Median progression-free survival (PFS): 3.6 months
Median overall survival (OS): 10.8 months

Among 42 patients with nonsquamous, taxane-naïve NSCLC, ORR was 29%, median response duration 12.8 months, median PFS 6.4 months, and median OS 14.8 months. (ascopubs.org)

Early phase I results for sigvotatug vedotin plus pembrolizumab showed a confirmed ORR of 42.9% in 21 efficacy-evaluable, previously untreated NSCLC patients without known EGFR or ALK alterations. This small, nonrandomized cohort had short follow-up, so the result remains preliminary. (ascopubs.org)

In June 2026, topline results from the 703-participant phase III SigVie-002 trial showed that sigvotatug vedotin did not significantly improve OS over docetaxel in the overall population with previously treated nonsquamous NSCLC. A more favorable trend in OS and PFS was reported among patients with only one previous line of therapy, but numerical results and full analyses had not yet been presented. No clear relationship between IB6 expression and response was observed. (pfizer.com)

Safety

Across the 117-patient phase I NSCLC population, 98% experienced a treatment-emergent adverse event (TEAE), 48% had a grade 3 or higher TEAE, and 16% had a grade 3 or higher treatment-related event. Frequently reported events included fatigue, peripheral sensory neuropathy, nausea, diarrhea, decreased appetite, and dyspnea. Peripheral neuropathy occurred in 44%, without grade 3 or higher cases; interstitial lung disease or pneumonitis occurred in 5%, including two grade 3 or higher events and one treatment-related death. Treatment-related events caused permanent discontinuation in 11%. (ascopubs.org)

Development status

Sigvotatug vedotin remains investigational. Despite the negative overall phase III monotherapy result, a separate phase III trial is evaluating it with pembrolizumab as first-line treatment for advanced NSCLC with PD-L1 tumor proportion score ≥50%. (pfizer.com)

Active trials using sigvotatug vedotin

Found 3 active trials using this drug:

AN INTERVENTIONAL OPEN-LABEL PHASE 1B/2 STUDY TO EVALUATE THE SAFETY, PHARMACOKINETICS, AND PRELIMINARY EFFICACY OF PF-08634404 IN COMBINATION WITH DIFFERENT ANTICANCER AGENTS IN PARTICIPANTS WITH ADVANCED SOLID TUMORS

Sponsor: Pfizer (industry) Phase: 1/2 Start date: Jan. 30, 2026

TrialFetch AI summary: Adults with previously untreated, unresectable stage IIIB/IIIC or metastatic NSCLC and no known actionable genomic alterations receive PF-08634404, an investigational PD-1/VEGF bispecific antibody, plus either sigvotatug vedotin, an integrin β6–targeted MMAE antibody–drug conjugate, or another protocol-specified anticancer agent. The latter cohort requires PD-L1 TPS ≥1%.

ClinicalTrials.gov ID: NCT07227298

AN OPEN-LABEL, RANDOMIZED, CONTROLLED PHASE 3 STUDY OF SIGVOTATUG VEDOTIN IN COMBINATION WITH PEMBROLIZUMAB COMPARED WITH PEMBROLIZUMAB MONOTHERAPY AS FIRST-LINE TREATMENT IN PARTICIPANTS WITH PD-L1 HIGH (≥50% OF TUMOR CELLS EXPRESSING PD-L1), LOCALLY ADVANCED, UNRESECTABLE, OR METASTATIC NON-SMALL CELL LUNG CANCER (BE6A LUNG-02)

Sponsor: Pfizer (industry) Phase: 3 Start date: May 4, 2025

TrialFetch AI summary: For patients with previously untreated, unresectable stage IIIB/IIIC or metastatic NSCLC and PD-L1 expression ≥50%, this trial compares pembrolizumab alone with pembrolizumab plus sigvotatug vedotin. Sigvotatug vedotin is an investigational integrin β6–targeting antibody–drug conjugate that delivers the microtubule-disrupting payload MMAE.

ClinicalTrials.gov ID: NCT06758401

A Phase 1 Study of SGN-B6A in Advanced Solid Tumors

Sponsor: Seagen, a wholly owned subsidiary of Pfizer (industry) Phase: 1 Start date: June 8, 2020

TrialFetch AI summary: This study enrolls patients with measurable metastatic or unresectable solid tumors and ECOG 0–1, including previously treated patients in monotherapy cohorts and treatment-naive patients with advanced NSCLC, head and neck, or esophageal cancer in combination cohorts. Patients receive sigvotatug vedotin, an integrin β6–targeting antibody–drug conjugate that delivers the microtubule-disrupting payload MMAE, alone or with pembrolizumab, with or without platinum chemotherapy.

ClinicalTrials.gov ID: NCT04389632