Top KOLs Discussing SigVie-002
SigVie-002 Key Slides & Visuals
ESMO 2026 slides
LBA68 presentation slides
| Endpoint | Sigvotatug vedotin (n=354) | Docetaxel (n=349) | HR (95% CI) |
|---|---|---|---|
| OS, median (primary) | 11.9 mo (10.1–14.0) | 11.5 mo (10.2–13.3) | 0.929 (0.767–1.126); stratified log-rank one-sided P = 0.226 (not met) |
| PFS by BICR, median (secondary) | 4.7 mo (4.2–6.0) | 4.2 mo (4.0–6.0) | 0.844 (0.699–1.019) |
| Confirmed ORR by BICR | 16% (12–20) | 13% (10–17) | — |
| Disease control rate | 69% (64–73) | 60% (55–65) | — |
| DOR, median (responders) | 8.3 mo (6.2–NR) | 10.1 mo (6.2–14.5) | — |
| Endpoint | Sigvotatug vedotin (n=236) | Docetaxel (n=241) | Unstratified HR (95% CI) |
|---|---|---|---|
| OS, median | 13.6 mo (10.7–16.4) | 11.1 mo (9.6–13.3) | 0.831 (0.658–1.049) |
| PFS, median | 5.9 mo (4.3–6.3) | 4.2 mo (4.0–6.0) | 0.795 (0.634–0.996) |
| Group | OS median, SV vs docetaxel | OS HR (95% CI) | PFS median, SV vs docetaxel | PFS HR (95% CI) |
|---|---|---|---|---|
| IB6-high (SV n=180; docetaxel n=186) | 12.1 vs 12.4 mo | 0.913 (0.695–1.199) | 5.6 vs 4.3 mo | 0.890 (0.683–1.159) |
| IB6-low (SV n=72; docetaxel n=67) | 13.4 vs 9.0 mo | 0.668 (0.424–1.054) | 4.3 vs 4.0 mo | 0.753 (0.476–1.192) |
Same slides also posted by @Tony_Calles, @Alfdoc2, @DrRiyazShah, @NReguart, @oncologician, @TommyJohn00.
Same slides also posted by @Alfdoc2.
Same slides also posted by @DrRiyazShah.
Physician reactions to SigVie-002
At ESMO 2026 (October 25, 2026)
SigVie-002 | #ESMO26 Sigvotatug vedotin vs docetaxel in advanced NSCLC: ❌ Primary OS endpoint not met. 📈 Encouraging OS/PFS trends in EGFR/ALK WT and 2L subgroups. 🧬 IB6 expression was not clearly predictive of efficacy. 🔬 Further combination trials warranted. #NSCLC #LungCancer
Another negative phase III trial in pretreated NSCLC! ❌ SigVie-002 sigvotatug vedotin vs docetaxel failed to meet its primary OS endpoint in non-squamous NSCLC. @peters_solange. The challenge of beating docetaxel with ADCs in 2L continues! #ESMO26 #LungCancer https://t.co/rmBBg7zn2E
Disappointing results from SigVie-002 at #ESMO26. @peters_solange presents the phase III trial of sigvotatug vedotin vs docetaxel in previously treated advanced nonsquamous NSCLC. No OS benefit: 11.9 vs 11.5 months (HR 0.93; p=0.226) No significant PFS improvement: 4.7 vs 4.2 months (HR 0.84) Exploratory analyses showed no clear efficacy trend according to integrin β6 (IB6) expression. Another reminder that promising ADC biology does not always translate into clinical benefit in phase III trials. #ESMOAmbassadors #ESMO26 #LungCancer #NSCLC #ADC
❌Completely negative phase III trial of sigvotatug vedotin (SV) vs docetaxel in previously treated NSCLC. 🔬 Explorative integrin beta-6 (IB6) expression not predictive of efficacy. #ESMO26 #LCSM https://t.co/EItPWw0TSu
@peters_solange on SV vs docetaxel. Docetaxel again proves difficult to topple. IB6 expression not helpful. But in EGFR and ALK potential signal. AEs similar, not really any benefit for SV. Also more ILD in Sv arm #LCSM #ESMO26 https://t.co/CtUjDmo9Ei
Context: on the LBA68 overall survival subgroup slide, the hazard ratio was 1.32 (95% CI 0.87–1.99) with EGFR or ALK alterations present and 0.85 (0.68–1.05) with them absent or unknown (exploratory, data cutoff May 18, 2026).
Phase 3 study of sigvotatug vedotin (SV) vs docetaxel (DTX) in previously treated nonsquamous non-small cell lung cancer (NSCLC) it was a negative study 😩 Solange Peters (CH) https://t.co/vGMu02Ojfn
#ESMO26 Dr. @peters_solange presents phase 3 study of sigvotatug vedotin (SV, integrin beta-6 ADC) vs docetaxel in previously treated non-squamous NSCLC. No difference in survival. Some signal in driver-negative NSCLC in 2L setting (vs 3L). #ESMOAmbassadors https://t.co/t2NW9Ye0xR
🆙#ESMO26 Proffered Paper I: #LCSM Mets 🔥SigVie-002: Phase 3 Study of Sigvotatug Vedotin (SV) vs Docetaxel (DTX) in Previously Treated Nonsquamous Non-Small Cell Lung Cancer (NSCLC) 🎙️ @peters_solange 🔢LBA68 🎯Primary OS Endpoint Not Met 🎯mOS 11.9 vs 11.5mo (HR 0.929, p=0.226; n=703) 🎯Post Hoc 2L Subgroup: OS 13.6 vs 11.1mo (HR 0.831), PFS HR 0.795 🎯Grade≥3 TRAEs 33% vs 36% ☑️NCT06012435 🔗 https://t.co/uGHKJfjhvW @OncoAlert @Larvol @myESMO @IASLC
Sigvotatug vedotin SV; SigVie-002; n703; in relapsed nonSq NSCLC; 1/3 were AGA post targeted Tx; #ESMO26 https://t.co/y4v68SveTy
After the June 22, 2026 topline announcement
JUST IN, via @BusinessWire: @pfizer Sigvotatug Vedotin SV, Integrin beta-6 (IB6) directed ADC in metastatic lung cancer with 1+ line fails to show OS vs. Docetaxel. Major setback for ADC and 1st-in-class target. @OncoAlert https://t.co/mHb77v8X37
Pfizer announces Phase III failure of Sigvotatug Vedotin in NSCLC (adenocarcinoma). ➡️Integrin Beta 6 is frequently expressed on NSCLC tumor cell membranes (according to the limited data available; https://t.co/QfOJLgLZsw) Or is it more complicated as for Nectin-4? ➡️However, SV does not appear very effective even in in vitro and in vivo preclinical assessments (https://t.co/qttruou48i). ➡️ORR in a large Phase I trial was only 19%, despite high expression prevalence (29% in taxane-naive adenocarcinoma; https://t.co/qttruou48i). In the press release: no meaningful impact of ITGB6 expression. My personal opinion: this is not a target issue but seems drug-related (low-efficacy drug)! I hope more ITGB6-directed ADCs are coming. We learn that the design of these drugs is key if the target is present. https://t.co/SY6GpUgoNC
IB6 targeting ADC Sigvotatug-Vedotin fails to improve OS in 2nd line NSCLC A biomarker free ADC development with weak payload: a predictable clinical trial failure. The SeaGen pipeline continues to be a source of great sorrow for drug development. Many lessons here. https://t.co/ni4HMjb7bn
Ph 3 SigVie-002 Press Release ▫️Sigvotatug vedotin (IB-6 directed ADC) failed to improve OS vs docetaxel in previously treated metastatic non-squamous NSCLC. ▫️? Signal observed in 2L setting. Negative study. Ongoing Ph 3 study of SV + pembro in 1L mNSCLC w/ PD-L1 ≥50% https://t.co/V9V3LPDbDx
SigVie-002 Trial Design
SigVie-002 asked whether sigvotatug vedotin, an antibody-drug conjugate directed at integrin beta-6 (IB6), could improve overall survival over docetaxel in previously treated non-squamous NSCLC. IB6 is expressed on about 90% of NSCLC tumors (Pfizer). The trial is sponsored by Seagen, a wholly owned subsidiary of Pfizer, and enrolled patients from March 6, 2024 to June 5, 2025. ClinicalTrials.gov lists 762 enrolled; the LBA68 analysis covers the 703 randomized patients. Results were presented by Solange Peters, MD, PhD, at ESMO 2026 (LBA68, Proffered paper 1: NSCLC, metastatic, October 25, 2026); Melissa L. Johnson (Nashville, USA) was the invited discussant.
Study Design
Global, randomized 1:1, open-label phase 3 (NCT06012435). N=703 (354 vs 349). Stratified by ECOG PS (0 vs 1), known EGFR or ALK alterations (present vs absent/unknown) and region.
Population
Advanced, unresectable or metastatic non-squamous NSCLC after platinum-based chemotherapy; a PD-(L)1 inhibitor was required without known AGAs, and ≥1 targeted therapy with a known AGA. No prior anti-microtubule agents; ECOG PS ≤1; no active CNS lesions.
Interventions
Sigvotatug vedotin 1.8 mg/kg (adjusted ideal body weight) IV every 2 weeks vs docetaxel 75 mg/m2 IV every 3 weeks.
Endpoints
Primary: overall survival. Secondary: PFS and ORR by BICR and investigator, duration of response, safety, quality of life. Exploratory: efficacy in the IB6-high subgroup.
Baseline
Median age 65 vs 63 years; any AGA 32% vs 27% (EGFR mutation 19% in each arm); one prior line 67% vs 69%; IB6-high 51% vs 53% (LBA68 slides).
Presenter
Solange Peters, MD, PhD (Lausanne University Hospital, CHUV, Switzerland). Invited discussant: Melissa L. Johnson (Nashville, USA).
Statements from the June 2026 announcement
"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."
— attributed to Solange Peters, MD, PhD (Lausanne University Hospital, CHUV) in the Pfizer press release"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."
— attributed to Jeff Legos, PhD, Chief Oncology Officer, Pfizer (sponsor statement)SigVie-002 in the News
SigVie-002 Questions
What is the SigVie-002 trial?
SigVie-002 (NCT06012435, previously called Be6A Lung-01) is a global, randomized, open-label phase 3 trial sponsored by Seagen, a wholly owned subsidiary of Pfizer. It compared sigvotatug vedotin, an antibody-drug conjugate directed at integrin beta-6 (IB6), with docetaxel in 703 patients with previously treated advanced non-squamous non-small cell lung cancer. Design: Trial Design.
What did SigVie-002 show at ESMO 2026?
The primary endpoint was not met. Median overall survival was 11.9 months with sigvotatug vedotin and 11.5 months with docetaxel (HR 0.929; one-sided P = 0.226; data cutoff May 18, 2026). Secondary endpoints, including progression-free survival by blinded central review (4.7 vs 4.2 months; HR 0.844), were not significantly improved. Figures: At a Glance.
Did second-line patients benefit?
In a post hoc analysis of the 477 second-line patients (68% of the trial), median overall survival was 13.6 vs 11.1 months (HR 0.831; 95% CI 0.658–1.049) and median PFS 5.9 vs 4.2 months (HR 0.795). This analysis was post hoc (not prespecified), so it can only generate hypotheses. No similar trend was seen in third-line or later patients (OS HR 1.187).
Did IB6 expression predict who benefited?
No. In an exploratory analysis, there was no clear relationship between IB6 expression level and efficacy, and the presenters reported this was consistent across the different thresholds tested. 72% of evaluable patients had IB6-high tumors.
Is sigvotatug vedotin FDA approved?
No. Sigvotatug vedotin is investigational and is not FDA approved for any use. Pfizer is testing it with pembrolizumab in an ongoing phase 3 trial in first-line NSCLC with PD-L1 TPS ≥50%, and the LBA68 authors support development with pembrolizumab or a PD-1/VEGF bispecific antibody in earlier settings.
What was the safety profile?
Per the LBA68 abstract, treatment-related adverse events of any grade occurred in 91% of patients with sigvotatug vedotin and 87% with docetaxel; grade ≥3 events in 33% and 36%; and events leading to discontinuation in 11% and 9%.