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 (SV; formerly SGN‑B6A) is an investigational antibody–drug conjugate (ADC) directed against integrin β6 (ITGB6/αvβ6), a tumor‑associated receptor overexpressed in multiple epithelial cancers and linked to poor prognosis. SV is in phase 1 evaluation across solid tumors and in a randomized phase 3 trial versus docetaxel in previously treated non‑small cell lung cancer (NSCLC). (pubmed.ncbi.nlm.nih.gov)

Mechanism of action

Target: Integrin αvβ6 (ITGB6), with antibody specificity that avoids other αv heterodimers. (pubmed.ncbi.nlm.nih.gov)
Payload/linker: Monomethyl auristatin E (MMAE) via a protease‑cleavable linker (a “vedotin” ADC). Internalization and payload release inhibit tubulin, causing G2/M arrest and apoptosis. (pubmed.ncbi.nlm.nih.gov)

Preclinical studies showed antitumor activity across NSCLC, pancreatic, pharyngeal and bladder models, and tolerability in cynomolgus monkeys with hematologic toxicities typical of MMAE ADCs. (pubmed.ncbi.nlm.nih.gov)

Efficacy

Phase 1 (SGNB6A‑001; NCT04389632) - NSCLC monotherapy: Confirmed ORR 19.0% (95% CI, 12.3–27.3) among 116 patients across dose levels. In a nonsquamous, taxane‑naive subset (n=42), confirmed ORR 31.0% (95% CI, 17.6–47.1) and median PFS 6.4 months (95% CI, 4.5–10.5). (onclive.com) - Combination with pembrolizumab (first‑line NSCLC, early cohort): Confirmed ORR 42.9% (95% CI, 21.8–66.0) in n=21 at ASCO 2025; follow‑up was short and DOR not yet reached. (onclive.com) - Early multi‑tumor phase 1 readouts (ASCO 2023) reported activity across NSCLC, esophageal, and head and neck cohorts and supported ongoing dose‑expansion. (ascopubs.org)

Phase 3 (Be6A Lung‑01; NCT06012435) - Ongoing randomized, open‑label trial comparing SV to docetaxel in previously treated (post‑platinum and anti‑PD‑(L)1) advanced NSCLC; primary endpoints include OS and ORR by BICR. Study start February 21, 2024; primary completion estimated March 12, 2026. (my.clevelandclinic.org)

Safety

In phase 1 (data through ASCO 2023 and subsequent updates): - Treatment‑emergent adverse events (TEAEs) occurred in ~89%, grade ≥3 in ~51% (related in ~22%); serious TEAEs in ~37% (related ~8%); discontinuation due to TEAEs ~6%. Most common TEAE was fatigue; most common grade ≥3 event was neutropenia (~8%). Peripheral sensory neuropathy and pneumonia were among discontinuation causes (~1% each). No treatment‑related deaths reported in the cited cutoff. (ascopubs.org) - Toxicities generally aligned with MMAE ADCs (e.g., fatigue, neutropenia, neuropathy); pneumonitis was observed infrequently in NSCLC cohorts. (onclive.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: Open-label study for adults with previously untreated locally advanced unresectable or metastatic squamous or nonsquamous NSCLC without actionable driver alterations, ECOG 0–1, measurable disease, and available PD-L1 status; Part B requires PD-L1 TPS ≥1%. Patients receive IV PF-08634404, an investigational bispecific PD-1/VEGF antibody, in combination with another anticancer agent, including sigvotatug vedotin, an integrin β6–directed MMAE antibody-drug conjugate, in one cohort.

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: This trial enrolls adults with previously untreated, locally advanced or metastatic NSCLC and high PD-L1 expression (≥50%), excluding those with common targetable mutations or prior checkpoint inhibitor therapy, to compare pembrolizumab alone versus pembrolizumab plus sigvotatug vedotin, an integrin beta-6–targeting antibody-drug conjugate.

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 trial enrolls adults with metastatic or unresectable solid tumors (including NSCLC, HNSCC, HER2-negative breast, esophageal, cutaneous SCC, ovarian, bladder, cervical, pancreatic, and gastric cancers), evaluating the antibody-drug conjugate sigvotatug vedotin—targeting integrin beta-6—with or without pembrolizumab and/or platinum chemotherapy. Eligibility varies by cohort, including both treatment-naïve and previously treated/refractory patients, with fresh or recent tumor biopsy required in some arms.

ClinicalTrials.gov ID: NCT04389632