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

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

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 Study of SGN-B6A Versus Docetaxel in Previously Treated Non-small Cell Lung Cancer (clinicaltrials.gov) - P3 | N=560 | Not yet recruiting | Sponsor: Seagen Inc.

New P3 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

Seagen Second Quarter 2023 Financial Results Demonstrate Exceptional Commercial Performance Driving Record Product Sales with Strong Growth and Momentum (Businesswire) - "Planned Initiation of a Phase 3 trial for SGN-B6A for Patients with Metastatic Non-Small Cell Lung Cancer: We plan to initiate a phase 3 trial evaluating SGN-B6A monotherapy compared to standard of care, docetaxel, in patients with previously treated non-small cell lung cancer in the fourth quarter of 2023....Of note, PADCEV sales in the second quarter of 2022 included $19 million in sales to another company for a clinical trial they are conducting, while no such sales were booked in the second quarter of 2023. TUKYSA performance reflects the important role it serves in the treatment of HER2-positivive metastatic breast cancer, competitive dynamics in this setting as well as early contributions from its colorectal cancer indication."

New P3 trial • Sales • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

SGN-B6A, an integrin beta-6 (ITGB6)-targeted antibody-drug conjugate (ADC), in patients with advanced solid tumors: Updated results from a phase 1 study (SGNB6A-001). (ASCO 2023) - P1 | "SGN-B6A demonstrated a manageable safety profile, and showed encouraging preliminary antitumor activity and response durability in dose escalation in a heavily pretreated population. Part B dose expansion cohorts in NSCLC, esophageal squamous cell carcinoma (ESCC), and HNSCC are ongoing. Clinical trial information: NCT04389632."

Clinical • Metastases • P1 data • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Fatigue • Gastrointestinal Cancer • Head and Neck Cancer • Hematological Disorders • Infectious Disease • Lung Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Pain • Pneumonia • Respiratory Diseases • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

"Lots of interest around this #Asco23 poster: $SGEN $PFE anti-ITGB6 ADC SGN-B6A. 23% ORR in head & neck, less impressive in NSCLC. Fair amount of tox" (@JacobPlieth)

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

Seagen Reports First Quarter 2023 Financial Results (Businesswire) - "UPCOMING DATA PRESENTATIONS: Presenting Multiple Abstracts at the ASCO Annual Meeting: Seagen will present over a dozen abstracts at the ASCO Annual Meeting taking place June 2-6, demonstrating continued progress of the company’s clinical pipeline. Two oral presentations will highlight long-term follow-up data from a clinical trial of PADCEV in combination with KEYTRUDA, EV-103 dose-escalation and Cohort A, and initial data from a Phase 2 basket study of TUKYSA and trastuzumab in previously treated HER2-positive metastatic biliary tract cancer. Additionally, updated Phase 1 data will be presented for SGN-B6A."

P1 data • P1/2 data • P2 data • Biliary Cancer • Biliary Tract Cancer • Bladder Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Seagen to Highlight Data From Oncology Portfolio and Pipeline at the 2023 American Society of Clinical Oncology Annual Meeting (Businesswire) - "Updated Phase 1 data will be presented for SGN-B6A, a wholly-owned, first-in-class vedotin ADC directed to integrin beta-6, a novel target that is highly expressed in multiple solid tumors....Additionally, initial data will be presented from studies evaluating Seagen’s approved medicines in potential new cancer types. Data from a Phase 2 basket study of TUKYSA® (tucatinib) and trastuzumab in previously treated HER2-positive metastatic biliary tract cancer will be featured in an oral presentation on Friday, June 2."

Clinical data • P1 data • P2 data • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

SGN-B6A induces immunogenic cell death as an additional mechanism of action (AACR 2023) - P1 | "The combination of SGN-B6A with immunotherapy may be utilized as a potential treatment for integrin-beta-6-expressing tumors including NSCLC, head and neck squamous cell carcinoma, and esophageal carcinoma. Altogether, our preclinical and initial clinical results support the ongoing evaluation of SGN-B6A as a single agent and in combination with immune checkpoint inhibitors."

Immunogenic cell death • IO biomarker • Esophageal Cancer • 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 • CALR • HMGB1

SGNB6A-001: A Study of SGN-B6A in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=572 | Recruiting | Sponsor: Seagen Inc. | N=355 ➔ 572

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 • Urothelial Cancer • Uterine Cancer • HER-2