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

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

A Study of SGN-B6A in Chinese Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=6 | Completed | Sponsor: Seagen, a wholly owned subsidiary of Pfizer | Active, not recruiting ➔ Completed

Trial completion • Esophageal Adenocarcinoma • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Frontline sigvotatug vedotin plus pembrolizumab vs pembrolizumab for non-small cell lung cancer with PD-L1 tumor proportion score ≥50%: phase III study design. (PubMed, Future Oncol) - P3 | "Approximately 714 patients will be randomized 1:1. The dual primary endpoints are progression-free survival as assessed by blinded independent central review per Response Evaluation Criteria in Solid Tumors v1.1 and overall survival; secondary endpoints include additional efficacy, safety and tolerability, pharmacokinetics, and immunogenicity endpoints.Clinical trial registration: NCT06758401 (https://clinicaltrials.gov/study/NCT06758401)."

IO biomarker • Journal • P3 data • Tumor proportion score • Lung 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

Molecular Portrait of Integrin Beta-6 (IB6): IB6 Expression Patterns and Its Association with Non-Small Cell Lung Cancer (NSCLC) Biomarkers: Insights from a US Real-World Data Study (AMP 2025) - "The investigational IB6-directed antibody-drug conjugate sigvotatug vedotin has shown encouraging activity in NSCLC (Peters, ASCO 2024)... In this sample of diverse US patients with mNSCLC, high IB6 expression was common, particularly in non-squamous histology, underscoring the potential of IB6 as a novel therapeutic target. Initial results support a correlation between IB6 expression by IHC and RNA sequencing. No notable trend was observed between IB6 expression status and PD-L1, TACSTD2, or cMET expression."

Biomarker • Clinical • IO biomarker • Real-world • Real-world evidence • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • ITGB6 • KRAS • PD-L1 • TACSTD2

A multi-integrin targeting peptide-drug conjugate induces durable tumor regression with a strong preclinical safety profile (SITC 2025) - "In head-to-head studies, PIP-MMAE outperformed clinical-stage benchmarks BT8009 (Nectin-4-targeting peptide-MMAE conjugate; Bicycle Therapeutics) and SGN-B6A (αvβ6 integrin-targeting ADC-MMAE; Pfizer).In a head and neck cancer model with high αvβ6 integrin expression, strong initial responses were observed with SGN-B6A treatment, but tumors eventually became resistant and continued to grow even when additional doses were administered. Finally, in repeated-dose toxicology studies, PIP-MMAE was well tolerated in both rats and NHPs with no indication of any PIP-related (target-dependent) toxicities.Conclusions PIP-MMAE demonstrates robust efficacy across various solid tumors, alongside a 'fast-in, fast-out' PK profile that confers remarkable safety. These preclinical data support the continued development of PIP-MMAE, with clinical trials planned to further evaluate its safety, PK, and anti-tumor activity in cancer patients.Ethics Approval All the procedures related..."

Preclinical • Head and Neck Cancer • Oncology • Solid Tumor • NECTIN4

Sigvotatug vedotin, an integrin-beta 6 directed antibody drug conjugate, demonstrates potent single-agent antitumor activity across NSCLC subtypes and the potential to combine with targeted therapies (AACR-NCI-EORTC 2025) - "SV is currently being evaluated in NSCLC as a monotherapy and NSCLC and HNSCC in combination with pembrolizumab. Additionally, SV may contribute to antitumor activity by depleting neighboring IB6-negative tumor cells via the bystander effect. These findings support the continued development of SV in NSCLC and provide scientific rationale to further explore SV efficacy in lung tumors with actionable genomic alterations."

Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • ALK • EGFR • KRAS

A novel Integrin beta-6-targeted antibody-drug conjugate featuring a topoisomerase I inhibitor, PBX-004 with potent antitumor activity in multiple preclinical solid tumor models (AACR-NCI-EORTC 2025) - "The anti-tumor activity of PBX-004 was comparable to, or exceeded, that of the MMAE-based ADC Sigvotatug Vedotin (SGN-B6A; Pfizer/Seagen) at equivalent dose levels. Enhanced efficacy is anticipated through a next-generation antibody and the novel PBX-7016 payload. PBX-004 may overcome the limitations of MMAE-based ADCs and offer a superior option for patients with various integrin beta-6–expressing solid tumors, including NSCLC, HNSCC, and TNBC."

Preclinical • Breast Cancer • Cervical Cancer • Colorectal Cancer • Gastric Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • ITGB6 • TOP1

PF-08052667: An antibody-drug conjugate optimized for intravesical delivery to treat non-muscle-invasive bladder cancer (ESMO 2025) - "PF-08052667 targets IB6 with the same antibody backbone as sigvotatug vedotin. The PF-08052667 design and functional data support its clinical development to evaluate its safety and anti-tumor activity in a phase I first-in-human study. Legal entity responsible for the study Pfizer Inc."

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

Unveiling integrin beta-6 (IB6): real-world data from the IB6 expression and clinical outcomes in non-small cell lung cancer study (ESMO 2025) - "Sigvotatug vedotin, an investigational IB6-directed antibody-drug conjugate, has shown encouraging activity in NSCLC (Peters, ASCO 2024)...Conclusions In this diverse patient population, high IB6 expression is common in mNSCLC, particularly in nonsquamous histology, underscoring the potential of IB6 as a novel biomarker and therapeutic target. Further investigation into IB6-directed therapies is warranted."

Clinical • Clinical data • Real-world • Real-world evidence • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ITGB6

Integrin-ß6 Modulates the Tumor Microenvironment and Serves as a Prognostic Marker in Lung Squamous Cell Carcinoma (IASLC-WCLC 2025) - "Interest in ITGB6 has recently grown with the development of sigvotatug vedotin, an ITGB6-targeted antibody-drug conjugate (ADC) conjugated to monomethyl auristatin E (MMAE), which has shown promising efficacy in heavily pretreated NSCLC...Conclusions : High ITGB6 expression is an independent poor prognostic marker of OS in LUSC and is associated with an immunosuppressive and fibrotic TME characterized by active CAFs and increased ECM remodeling. These findings suggest that ITGB6 may not only serve as a therapeutic target but also as a biomarker for patient stratification in LUSC, particularly in the context of ADC therapy."

Biomarker • Tumor microenvironment • Fibrosis • Non Small Cell Lung Cancer • Oncology • CAFs • CAV1 • CD4 • ITGB6

A Study of SGN-B6A in Chinese Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=6 | Active, not recruiting | Sponsor: Seagen, a wholly owned subsidiary of Pfizer | Trial completion date: Aug 2025 ➔ Nov 2025 | Trial primary completion date: Aug 2025 ➔ Nov 2025

Trial completion date • Trial primary completion date • Esophageal Adenocarcinoma • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Be6A Lung-01: A Study of SGN-B6A Versus Docetaxel in Previously Treated Non-small Cell Lung Cancer (clinicaltrials.gov) - P3 | N=703 | Active, not recruiting | Sponsor: Seagen, a wholly owned subsidiary of Pfizer | N=470 ➔ 703

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

Development of a novel integrin beta-6 IHC assay for clinical evaluation of sigvotatug vedotin in nonsquamous non-small cell lung cancer specimens (ECP 2025) - "The novel Integrin Beta-6 IHC 6.2A1 pharmDx assay demonstrated high sensitivity, specificity, and precision for the detection of IB6 expression. The assay is suitable for testing of nsqNSCLC subjects for investigational use in an ongoing SV phase 3 trial."

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

SGNB6A-001: A Study of Sigvotatug Vedotin in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=1006 | Recruiting | Sponsor: Seagen, a wholly owned subsidiary of Pfizer | Trial completion date: May 2028 ➔ Mar 2029 | Trial primary completion date: Aug 2026 ➔ Jun 2027

Trial completion date • Trial primary completion date • Bladder Cancer • Breast Cancer • Cervical Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Head and Neck Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Adenocarcinoma • Pancreatic Cancer • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer • Uterine Cancer • HER-2

Sigvotatug Vedotin: “Comparable ORRs for TPS ≥1 & TPS <1” Non-small cell lung cancer (Pfizer) - Q2 2025 Results

P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Sigvotatug Vedotin: Data from P3 trial (NCT06012435) for 2L+ NSCLC in 2026 (Pfizer) - Q2 2025 Results

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

Be6A Lung-01: A Study of SGN-B6A Versus Docetaxel in Previously Treated Non-small Cell Lung Cancer (clinicaltrials.gov) - P3 | N=470 | Active, not recruiting | Sponsor: Seagen, a wholly owned subsidiary of Pfizer | Recruiting ➔ Active, not recruiting

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

BE6A LUNG-02: This is a Study to Learn About How the Combination of the Study Medicines Sigvotatug Vedotin Plus Pembrolizumab Works in People With Non-small Cell Lung Cancer With High Levels of PD-L1. (clinicaltrials.gov) - P3 | N=714 | Recruiting | Sponsor: Pfizer | Not yet recruiting ➔ Recruiting

Enrollment open • Monotherapy • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

SGNB6A-001: A Study of SGN-B6A in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=1006 | Recruiting | Sponsor: Seagen, a wholly owned subsidiary of Pfizer | Trial primary completion date: Nov 2026 ➔ Aug 2026

Trial primary completion date • Bladder Cancer • Breast Cancer • Cervical Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Head and Neck Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Adenocarcinoma • Pancreatic Cancer • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer • Uterine Cancer • HER-2

Sigvotatug vedotin: Initiation of P3 trial (NCT06758401) for 1L PD-L1-high NSCLC in H1 2025 (Pfizer) - Q1 2025 Results

Trial initiation date • Lung Cancer • Non Small Cell Lung Cancer • Oncology

PF-08046876: A new camptothecin antibody-drug conjugate directed to integrin beta-6 with potent antitumor activity in multiple preclinical solid tumor models (AACR 2025) - "PF-08046876 leverages the same antibody backbone from Sigvotatug Vedotin (SV) and is specific for IB6 but does not bind other alpha-v family members. These results suggest that PF-08046876 is promising ADC for the treatment of multiple carcinomas and supports further clinical investigation. A Phase 1, first-in-human study is planned to evaluate the safety and anti-tumor activity of PF-08046876."

Preclinical • Cervical Cancer • Gastric Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • TOP1

Be6A Lung-01: A Study of Sigvotatug Vedotin Versus Docetaxel in Previously Treated Non-small Cell Lung Cancer (clinicaltrials.gov) - P3 | N=670 | Recruiting | Sponsor: Seagen, a wholly owned subsidiary of Pfizer | Trial completion date: Jul 2028 ➔ Mar 2028 | Trial primary completion date: Jul 2026 ➔ Mar 2026

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

A Study of SGN-B6A in Chinese Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=6 | Active, not recruiting | Sponsor: Seagen Inc. | Recruiting ➔ Active, not recruiting | N=12 ➔ 6 | Trial completion date: Oct 2025 ➔ Jun 2025 | Trial primary completion date: Oct 2025 ➔ Jun 2025

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Esophageal Adenocarcinoma • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck