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

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

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 | Not yet recruiting | Sponsor: Pfizer | Initiation date: Jan 2025 ➔ May 2025

Monotherapy • Trial initiation date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

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 | Not yet recruiting | Sponsor: Pfizer

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

Pfizer ADC new drug substance 'Sigbotaug Vedotin' enters domestic lung cancer phase 3 trial [Google translation] (HIT News) - "Pfizer's phase 3 clinical trial for non-small cell lung cancer (NSCLC) treatment of 'sigvotatug vedotin (SGN-B6A),' a new antibody-drug conjugate (ADC) drug currently under development, is beginning. On the 13th, the Ministry of Food and Drug Safety approved a phase 3 clinical trial plan to confirm the safety and efficacy of sigbotatug vedotin as a second-line or higher treatment for non-small cell lung cancer patients...The research team set the primary efficacy endpoints of this study as overall survival (OS) and objective response rate (ORR) assessed by an independent central blinded evaluation (BICR). Key secondary efficacy endpoints include progression-free survival (PFS) by BICR and duration of response (DoR) by BICR."

New P3 trial • Non Small Cell Lung Cancer

Sigvotatug vedotin may eliminate TGFβ-dependent immunosuppression in the tumor microenvironment by eliminating integrin-β6 (IB6) expressing cells, but not through direct TGFβ signaling blockade (SITC 2024) - "In vitro and in vivo data shown here suggest the antibody backbone of SV may not provide robust blockade of the αvβ6/TGFB axis. However, these data support the potential for immunomodulation through ADC killing of IB6 expressing cancer cells, removing a potent axis of TGFβ release."

Biomarker • IO biomarker • Tumor microenvironment • Oncology • CD8 • TGFB1 • VTCN1

Be6A Lung-01, a phase III study of sigvotatug vedotin (SV), an investigational antibody-drug conjugate (ADC) versus docetaxel in patients (pts) with previously treated non-small cell lung cancer (NSCLC) (ESMO 2024) - P3 | "The key secondary endpoint is PFS by BICR per RECIST v1.1; other secondary endpoints include confirmed ORR, PFS by investigator, DOR by BICR and investigator per RECIST v1.1, safety, and patient-reported outcomes. Enrollment has begun in the US and the EU and is planned for other regions, including APAC and LATAM."

Clinical • P3 data • 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=12 | Recruiting | Sponsor: Seagen Inc. | Not yet recruiting ➔ Recruiting

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

A Study of SGN-B6A in Chinese Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=12 | Not yet recruiting | Sponsor: Seagen Inc.

Metastases • New P1 trial • Esophageal Adenocarcinoma • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

SGNB6A-001: A Study of SGN-B6A in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=824 | Recruiting | Sponsor: Seagen Inc. | Trial completion date: Oct 2028 ➔ Feb 2028

Metastases • Trial completion date • Bladder Cancer • Breast Cancer • Cervical Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Head and Neck Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • 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

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

Sixteen Researchers from Florida Cancer Specialists & Research Institute Share Cancer Care Discoveries at 2024 ASCO Annual Meeting (PRNewswire) - "Florida Cancer Specialists & Research Institute, LLC (FCS) physicians will present findings from multiple clinical studies that are contributing to global advancements in cancer care at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago. Clinical research originating from trials conducted at the three FCS Phase 1 Drug Development Units and late-phase studies at FCS clinics throughout Florida are among those being published or presented during the five-day international gathering of oncology physicians and professionals."

Clinical data • P1 data • P1/2 data • Breast Cancer • Liver Cancer • Non Small Cell Lung Cancer • Solid Tumor

Pfizer's potential "first-in-class" ADC therapy approved for clinical use in China [Google translation] (163.com) - "Today (April 19), the official website of the Center for Drug Evaluation (CDE) of the China State Food and Drug Administration announced that SGN-B6A, a Class 1 new drug applied by Seagen, has received implicit approval for clinical trials and is planned to be developed to treat adult patients with advanced solid tumors."

New trial • Oncology • Solid Tumor

Pfizer Highlights Progress in Accelerating Breakthrough Cancer Medicines at ASCO 2024 Annual Meeting (Pfizer Press Release) - "Pfizer Inc...highlights its progress in advancing new potential standards of care in Oncology at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, taking place May 31 to June 4 in Chicago....Pfizer will also present Phase 1 data for several priority pipeline therapies, including oral presentations with updated results for sigvotatug vedotin (B6A; integrin beta-6 [IB6]-directed ADC) in NSCLC and data for PF-07248144, a potential first-in-class KAT6 inhibitor, in hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC)."

P1 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • 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=824 | Recruiting | Sponsor: Seagen Inc. | Trial completion date: Oct 2024 ➔ Oct 2028 | Trial primary completion date: Jul 2024 ➔ Nov 2026

Metastases • Trial completion date • Trial primary completion date • Bladder Cancer • Breast Cancer • Cervical Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Head and Neck Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • 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

Pfizer Oncology Hosts Innovation Day, Highlighting Fully Integrated Organization, Robust Portfolio, and Strategic Priorities to Drive Long-Term Sustainable Growth (Pfizer Press Release) - "The company outlined potential significant catalysts anticipated through the first half of 2025, including: Six anticipated Phase 3 study starts, which includes three new trials recently initiated for key pipeline assets: atirmociclib (CDK4i) in second-line hormone receptor positive (HR+) mBC, sigvotatug vedotin (B6A; integrin beta-6 (IB6)-directed ADC) in second/third-line non-small cell lung cancer (NSCLC), and ELREXFIO in patients with multiple myeloma after their cancer progresses on anti-CD38 treatment (MagnetisMM-32 trial). Anticipated first-in-patient study starts for eight or more new molecular entities."

New trial • Trial status • Breast Cancer • Hematological Malignancies • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Multiple Myeloma • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Be6A Lung-01: A Study of SGN-B6A Versus Docetaxel in Previously Treated Non-small Cell Lung Cancer (clinicaltrials.gov) - P3 | N=600 | Recruiting | Sponsor: Seagen Inc. | Not yet recruiting ➔ Recruiting | Trial completion date: Jan 2029 ➔ Jul 2028 | Initiation date: Nov 2023 ➔ Mar 2024 | Trial primary completion date: Nov 2026 ➔ Jul 2026

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

Seagen Third Quarter 2023 Financial Results Reflect Strong Product Sales Growth, and Significant Portfolio and Pipeline Progress (Seagen Press Release) - "The Company expects to initiate a phase 3 trial for SGN-B6A, a novel, vedotin ADC targeting integrin beta-6, as a monotherapy in previously treated patients with NSCLC before the end of 2023....The Company initiated a phase 1 trial for SGN-EGFRd2, a gamma delta bispecific T-cell engager for EGFR-expressing solid tumors. Year to date, the Company has submitted INDs for three novel targeted cancer therapies, including SGN-EGFRd2, SGN-35T and SGN-CEACAM5C, with the goal of submitting one additional IND before year end."

IND • Trial status • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

SGN-B6A: A Vedotin Antibody-Drug Conjugate that Targets Integrin Beta-6 & Shows Clinical Efficacy in Multiple Solid Tumor Indications (ADC-USA 2023) - "SGN-B6A is an investigational, first-in-class ADC, that shows high specificity towards integrin beta-6; Overview of SGN-B6A preclinical and clinical safety and efficacy data; Rationale for clinical combination between SGN-B6A and CPIs"

Clinical • Oncology • Solid Tumor

SGNB6A-001: A Study of SGN-B6A in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=1006 | Recruiting | Sponsor: Seagen Inc. | N=572 ➔ 1006

Enrollment change • Metastases • Bladder Cancer • Breast Cancer • Cervical Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Head and Neck Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Non-melanoma Skin Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • 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