sigvotatug vedotin (PF-08046047) / Pfizer - LARVOL DELTA

SGN-B6A: A New Vedotin Antibody-Drug Conjugate Directed to Integrin Beta-6 for Multiple Carcinoma Indications. (PubMed, Mol Cancer Ther) - P1 | "Hematologic toxicities typical of MMAE ADCs were dose limiting, and no significant target-mediated toxicity was observed. A phase 1 first-in-human study is in progress to evaluate the safety and antitumor activity of SGN-B6A in a variety of solid tumors known to express integrin beta-6 (NCT04389632)."

Journal • Bladder Cancer • Genito-urinary Cancer • Hematological Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor

A randomized, phase 3, open-label study to evaluate sigvotatug vedotin compared with docetaxel in adult participants with previously treated non-small cell lung cancer (Be6A Lung-01) (ChiCTR) - P3 | N=100 | Recruiting | Sponsor: Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences); Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sci

New P3 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK

Sigvotatug vedotin (SV), an investigational integrin beta-6 (IB6)–directed antibody‒drug conjugate (ADC), and pembrolizumab combination therapy: Initial results from an ongoing phase 1 study (SGNB6A-001). (ASCO 2025) - P1, P3 | "SV+P demonstrated manageable safety and encouraging preliminary efficacy. These data support the ongoing phase 3 Be6A-Lung-02 study (NCT06758401) comparing SV+P vs P as first-line treatment for pts with PD-L1 high (TPS≥50) advanced NSCLC."

Combination therapy • P1 data • Head and Neck Cancer • Interstitial Lung Disease • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Efficacy and safety of sigvotatug vedotin, an investigational ADC, in NSCLC: Updated phase 1 results (SGNB6A-001). (ASCO 2024) - P1, P3 | "SV continues to demonstrate encouraging antitumor activity and a manageable safety profile in pts with NSCLC. Data at 1.8 mg/kg AiBW 2Q4W support initiation of the Ph 3 SGNB6A-002 study in 2/3L NSCLC (NCT06012435) and combination with pembrolizumab in earlier settings."

Clinical • P1 data • Fatigue • Head and Neck Cancer • Hematological Disorders • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Pneumonia • Pulmonary Disease • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

ITGB6 Expression and Real-World Outcomes in Non-Small Cell Lung Cancer (IASLC-WCLC 2026) - "ITGB6-directed antibody-drug conjugates such as sigvotatug vedotin are in clinical trials for non-small cell lung cancer (NSCLC)...ITGB6 shows opposing prognostic effects in LUAD and LUSC but is not predictive of rwOS with IO or EGFR TKI. Shorter EGFR TKI duration with high ITGB6 may reflect differential TKI sensitivity."

Clinical • IO biomarker • Real-world • Real-world evidence • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • ITGB6 • KEAP1 • PD-L1 • STK11 • TP53

Sigvotatug vedotin: “Primary OS endpoint not met in overall population”; Non-small cell lung cancer (Pfizer) - Q2 2026 Results: “Median survival benefit (13.6 vs. 11.1 months) suggests clinically meaningful activity with SV”

P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Sigvotatug vedotin: Initiation of trial for 1L NSCLC (TPS all comers) in H2 2026 (Pfizer) - Q2 2026 Results

New trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology

PF-08046876, a differentiated integrin beta-6 antibody-drug conjugate delivering a potent camptothecin payload optimized for bystander effect and reduced drug efflux. (PubMed, Mol Cancer Ther) - "PF-08046876 leverages the same antibody backbone from sigvotatug vedotin (SV) and binds IB6 without cross-reactivity to other alpha-v integrin complexes. In preclinical studies, PF-08046876 has demonstrated significant antitumor activity both in vitro and in vivo across multiple tumor models with IB6 expression, including non-small cell lung (NSCLC), head and neck squamous cell (HNSCC), urothelial (UC), pancreatic (PDAC), and esophageal (ESCA) carcinomas. These findings support further clinical development of PF-08046876 as a promising therapeutic candidate for the treatment of IB6-expressing solid tumors."

Journal • Esophageal Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • TOP1

Symbiotic-Lung-20: A Study to Learn About the Study Medicine Called PF-08634404 in Combination With Different Anticancer Agents in Advanced Cancers (clinicaltrials.gov) - P1/2 | N=162 | Recruiting | Sponsor: Pfizer

Trial initiation date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

A Study to Learn About the Study Medicine Called PF-08634404 in Combination With Different Anticancer Agents in Advanced Cancers (clinicaltrials.gov) - P1/2 | N=162 | Not yet recruiting | Sponsor: Pfizer

New P1/2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Symbiotic-Lung-20: A Study to Learn About the Study Medicine Called PF-08634404 in Combination With Different Anticancer Agents in Advanced Cancers (clinicaltrials.gov) - P1/2 | N=53 | Recruiting | Sponsor: Pfizer

New P1/2 trial • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

C6461020: A Study to Learn About the Study Medicine Called PF-08634404 in Combination With Different Anticancer Agents in Advanced Cancers (clinicaltrials.gov) - P1/2 | N=162 | Recruiting | Sponsor: Pfizer | Not yet recruiting ➔ Recruiting

Enrollment open • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

Symbiotic-Lung-20: A Study to Learn About the Study Medicine Called PF-08634404 in Combination With Different Anticancer Agents in Advanced Cancers (clinicaltrials.gov) - P1/2 | N=162 | Recruiting | Sponsor: Pfizer | N=53 ➔ 162

Enrollment change • Trial initiation date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

Pfizer Announces Topline Phase 3 Results for Sigvotatug Vedotin in Previously Treated Metastatic Non-Squamous Non-Small Cell Lung Cancer (Businesswire) - "In the overall population, sigvotatug vedotin did not show a statistically significant improvement in the primary endpoint of overall survival (OS) compared to docetaxel. The safety profile of sigvotatug vedotin was manageable and consistent with prior studies. Encouragingly, in patients who received only one prior line of systemic therapy, which represents two-thirds of the study population, a stronger trend was observed for OS and progression-free survival (PFS) for sigvotatug vedotin over docetaxel. In the exploratory analysis, no clear IB6 expression-response relationship was observed. Detailed results from SigVie-002 will be submitted for presentation at a future medical congress."

P3 data: top line • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer

Mapping the antibody-drug-conjugates landscape in non-small cell lung cancer: Where are we and where are we going? (PubMed, Cancer) - "Late-phase ADCs include trastuzumab deruxtecan (targeting HER2 [human epidermal growth factor receptor 2]), datopotamab deruxtecan and sacituzumab govitecan (targeting TROP2 [trophoblast cell-surface antigen 2]), patritumab deruxtecan (targeting HER3), telisotuzumab vedotin (targeting c-MET [cellular-mesenchymal epithelial transition factor]), and sigvotatug vedotin (targeting IB6 [integrin beta-6]). Ongoing, biomarker-driven trials and combination strategies with immunotherapy or tyrosine kinase inhibitors hold the potential to further enhance the efficacy of ADCs. In this review, the authors highlight the current landscape and future directions of ADCs in NSCLC, emphasizing available results for compounds in late-stage clinical development and different disease settings."

IO biomarker • Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ERBB3 • HER-2 • MET

Sigvotatug vedotin (SV), an investigational integrin beta-6 (IB6)─directed antibody-drug conjugate (ADC), plus pembrolizumab: Updated results from the phase 1 study (SGNB6A-001). (ASCO 2026) - P1, P3 | "SV+P continued to show manageable safety and encouraging antitumor activity in treatment-naive NSCLC across PD-L1 TPS and histologies. This supports the ongoing phase 3 SigVie-003 study (NCT06758401) of SV+P vs P for treatment-naive aNSCLC with PD-L1 TPS ≥50% as well as further investigation in the enrolling phase 1 cohorts and future studies."

ADC • P1 data • Alopecia • Esophageal Cancer • Head and Neck Cancer • Immunology • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

SigVie-003: Phase 3 trial of frontline sigvotatug vedotin plus pembrolizumab vs pembrolizumab alone in non-small cell lung cancer (NSCLC) with PD-L1 TPS ≥50%. (ASCO 2026) - P3 | "A genAI tool (2/27/25; Pfizer; GPT-4o) developed the 1st draft; authors assume content responsibility. Frontline sigvotatug vedotin plus pembrolizumab vs pembrolizumab for non-small cell lung cancer with PD-L1 tumor proportion score ≥50%: phase III study design, Reck M, et al., Future Oncol, Dec 13, 2025, Taylor & Francis, reprinted by permission of the publisher Informa UK Limited trading as Taylor & Francis Ltd."

IO biomarker • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • PD-L1 • ROS1

Sigvotatug vedotin: Data readout from P3 Be6A LUNG-01 trial (NCT06012435) for 2L+ non-squamous NSCLC in 2026 (Pfizer) - Q1 2026 Results

P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Assessment of tumor heterogeneity for Integrin beta-6 expression in non-squamous non-small cell lung cancer specimens using an investigational Integrin beta-6 IHC assay (AACR 2026) - "An investigational ADC, sigvotatug vedotin (SV), is currently being studied in non-small cell lung cancer (NSCLC) and is directed to the novel target integrin beta-6 (IB6)...There was no significant difference in the detection of IB6 positivity across ischemia times of 0.5-72 hours and 10% NBF fixation times of 6-72 hours.Integrin Beta-6 IHC 6.2A1 pharmDx demonstrates high reproducibility with respect to tissue heterogeneity around the ≥50% diagnostic cutoff, indicating there is uniformity in biomarker expression across and within tumor sites for nsqNSCLC. These preliminary findings may provide confidence that assessment of IB6 expression can be reliably performed across tumor sites and within tumor sites."

Heterogeneity • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

First-in-Human, Phase I Study of Sigvotatug Vedotin, an Integrin Beta-6-Directed Antibody-Drug Conjugate: Results From Dose Expansion in Advanced Non-Small Cell Lung Cancer. (PubMed, J Clin Oncol) - "SV demonstrated a manageable safety profile and promising antitumor activity with durable responses in aNSCLC. PK and clinical data support further investigation with the recommended 1.8-mg/kg AiBW once every 2 weeks dosing regimen."

First-in-human • Journal • P1 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

An Integrin β6-targeted antibody-drug conjugate optimized for intravesical delivery to treat non-muscle invasive bladder cancer. (PubMed, Mol Cancer Ther) - P1 | "IB6 is being actively tested in lung cancer with the antibody-drug conjugate (ADC) sigvotatug vedotin. The combination of highly potent PF-08052667 with bladder prewash demonstrated enhanced in vivo efficacy while maintaining minimal systemic exposure and no systemic toxicity. Together, the results position PF-08052667 as a potential first-in-class ADC optimized for intravesical delivery and support further clinical examination in an ongoing Phase I trial testing safety and efficacy in BCG-unresponsive and BCG-exposed NMIBC (NCT07206225)."

Journal • Bladder Cancer • Genito-urinary Cancer • Lung Cancer • Oncology • Solid Tumor

Advancing next-generation pipeline of novel mechanisms and differentiated combinations across solid tumors (Businesswire) - "Updated Phase 2 data for PF‑08634404 (PF’4404), a novel bispecific antibody targeting PD-1 and VEGF, as monotherapy in first-line PD-L1-expressing NSCLC...Updated results from a Phase 1 study of sigvotatug vedotin (SV), a novel integrin β6 (IB6)–directed ADC, in combination with pembrolizumab in NSCLC...The first results from a Phase 2 study of neoadjuvant atirmociclib, a highly selective CDK4 inhibitor, in combination with letrozole versus letrozole alone in people with hormone receptor-positive (HR+), HER2- breast cancer....Findings from a Phase 1b study of a brain-penetrant MEK inhibitor, PF-07799544 (polfurmetinib), plus a next-generation BRAF inhibitor, PF-07799933 (claturafenib), in advanced BRAF-mutant melanoma."

P1 data • P2 data • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Melanoma • Non Small Cell Lung Cancer

Integrin beta-6: Its emerging role as a therapeutic target in solid tumors. (PubMed, Cancer Treat Rev) - "Sigvotatug vedotin, an IB6-directed antibody-drug conjugate linked to a monomethyl auristatin E payload showed promising efficacy in a phase 1 study in patients with advanced solid tumors, particularly non-small cell lung cancer, and is being investigated in two phase 3 studies. Additionally, several other IB6-directed antibody-drug conjugates have demonstrated antitumor activity in preclinical studies and are entering the clinical stage of development. Results from these studies will enable greater understanding of IB6 as an anticancer therapeutic target, as well as IB6 expression as a potential biomarker."

Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A phase Ib/II trial of a PD-1/VEGF bispecific antibody (PF-08634404) in combination with anticancer agents in first-line (1L) for advanced solid tumors (Symbiotic-Lung-20) (ELCC 2026) - P1/2 | "In parts A and B, PF-08634404 is combined with different vedotin-based antibody-drug conjugates (ADCs; sigvotatug vedotin and PDL1V) in patients (pts) with pathologically confirmed locally advanced (stage IIIB/IIIC) or metastatic (stage IV) NSCLC who have not received prior systemic therapy in 1L. Key secondary endpoints include DCR, DOR, and PFS all by investigator, and OS. Enrollment has begun."

Bispecific • Clinical • Combination therapy • IO biomarker • Metastases • P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-1

C6461020: A Study to Learn about the Study Medicine called PF-08634404 in Combination With Different Anticancer Agents in Advanced Cancers (clinicaltrialsregister.eu) - P1/2 | N=43 | Not yet recruiting | Sponsor: Pfizer Inc.

New P1/2 trial • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1