PF-08046054 / Pfizer - LARVOL DELTA

Interim results of PDL1V (PF-08046054), a vedotin-based ADC targeting PD-L1, in patients with NSCLC in a phase 1 trial. (ASCO 2025) - P1 | "Clinical Trial Registration Number: NCT05208762 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Initial safety and efficacy of PDL1V (PF-08046054), a vedotin-based ADC targeting PD-L1, in combination with pembrolizumab in patients with recurrent or metastatic (R/M) HNSCC. (ASCO 2025) - P1 | "Clinical Trial Registration Number: NCT05208762 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • Combination therapy • Metastases • Head and Neck Cancer • Squamous Cell Carcinoma of Head and Neck

Nonclinical characterization of the secondary mechanisms of action of PF-08046054 (PDL1V), a novel vedotin ADC directed to PD-L1 that selectively depletes tumor cells without depleting healthy immune cells (AACR 2025) - P1 | "PDL1V is a novel vedotin antibody drug-conjugate (ADC) currently in Phase I clinical development for advanced solid tumors as a monotherapy or in combination with pembrolizumab (NCT05208762). Since T cell-driven antitumor immunity is a key driver for the efficacy of PD-(L)1 blockade, these data suggest PDL1V is a promising combination partner with anti-PD-1 immunotherapies such as pembrolizumab. Future studies will evaluate the effects of PDL1V on immunosuppressive cells, including regulatory T cells and myeloid derived suppressor cells, and the pharmacodynamic effects of PDL1V in syngeneic mouse xenograft models.Ethics Approval: All procedures performed on animals were in accordance with regulations and established guidelines and were reviewed and approved by an Institutional Animal Care and Use Committee or through an ethical review process."

Clinical • Immune cell • IO biomarker • Tumor cell • Oncology • Solid Tumor • CALR • CD4 • CD8 • HMGB1 • PD-L1

PDL1V (PF-08046054): A Firstin- Class PD-L1-Directed ADC with Promising Activity in 2L+ NSCLC (ADC London 2025) - "• PDL1V was engineered for enhanced potency through increased internalization and payload delivery • PDL1V is efficacious across a broad range of PD-L1 expression & induces MMAE-mediated immune activation in vivo • Interim results of a phase 1 Study of PDL1V in patients with PDL1-expressing solid tumours demonstrate promising activity in 2L+ NSCLC"

IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

SGNPDL1V-001: A Study of SGN-PDL1V in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=315 | Recruiting | Sponsor: Seagen Inc. | Trial completion date: Dec 2027 ➔ Nov 2028 | Trial primary completion date: Jul 2025 ➔ Nov 2027

Trial completion date • Trial primary completion date • Breast Cancer • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Cancer • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • PD-L1

SGNPDL1V-001: A Study of PF-08046054/SGN-PDL1V in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=438 | Recruiting | Sponsor: Seagen Inc. | Trial completion date: Dec 2026 ➔ Dec 2027

Metastases • Trial completion date • Breast Cancer • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • PD-L1

Interim results of a phase I study of SGN-PDL1V (PF-08046054) in patients with PDL1-expressing solid tumors (ESMO 2024) - P1 | "Single agent SGN-PDL1V was generally well tolerated with a manageable safety profile. Encouraging preliminary antitumor activity was observed. Enrollment in the phase 1 study continues."

Clinical • IO biomarker • P1 data • Breast Cancer • 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 • Triple Negative Breast Cancer • PD-L1

Pfizer Highlights Diverse Oncology Portfolio and Combination Approaches at ESMO 2024 (Pfizer Press Release) - "Pfizer will also present early clinical-stage research for a number of priority pipeline areas, including encouraging Phase 1 results of the potential first-in-class antibody-drug conjugate (ADC) candidate SGN-PDL1V (PF-08046054) in NSCLC and head and neck squamous cell carcinoma (HNSCC); initial data for the investigational ADC disitamab vedotin in combination with KEYTRUDA (pembrolizumab) in human epidermal growth factor receptor 2 (HER2)-expressing locally advanced or metastatic urothelial cancer (la/mUC); and the first data combining atirmociclib, our highly-selective cyclin-dependent kinase 4 (CDK4) inhibitor (CDK4i), with a novel CDK2 inhibitor (CDK2i) in hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer (MBC) from a Phase 1 dose-escalation study."

P1 data • P2 data • Breast Cancer • Genito-urinary Cancer • Head and Neck 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 • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer

SGNPDL1V-001: A Study of PF-08046054/SGN-PDL1V in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=438 | Recruiting | Sponsor: Seagen Inc. | N=322 ➔ 438

Enrollment change • Metastases • Breast Cancer • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • PD-L1

Phase 1 study of SGN-PDL1V, a novel, investigational vedotin antibody–drug conjugate directed to PD-L1, in patients with advanced solid tumors (SGNPDL1V-001, trial in progress). (ASCO 2022) - P1 | "Objective response rate will be analyzed by tumor type, dose levels, and schedules. Enrollment for Part A is ongoing at sites in North America and is planned in Europe."

Clinical • IO biomarker • P1 data • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Head and Neck Cancer • Immune Modulation • Inflammation • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

SGNPDL1V-001: A Study of SGN-PDL1V in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=305 | Not yet recruiting | Sponsor: Seagen Inc. | Initiation date: Aug 2022 ➔ Nov 2022

Trial initiation date • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

SGNPDL1V-001: A Study of SGN-PDL1V in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=315 | Recruiting | Sponsor: Seagen Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Breast Cancer • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer

A Study of SGN-PDL1V in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=305 | Recruiting | Sponsor: Seagen Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Seagen Reports Fourth Quarter and Full Year 2021 Financial Results (Businesswire) - "Initial data from the innovaTV 207 phase 2 trial of TIVDAK in solid tumors will be presented at the Multidisciplinary Head and Neck Cancers Symposium to be held February 24-26. Initiated Phase 1 Trials with Novel Antibody-Drug Conjugates (ADCs): In January 2022, the Company initiated phase 1 clinical trials of two novel ADCs, SGN-PDL1V and SGN-B7H4V, for advanced solid tumors."

P2 data • Trial initiation date • Oncology • Solid Tumor

A Study of SGN-PDL1V in Advanced Solid Tumors (clinicaltrials.gov) - P1; N=305; Not yet recruiting; Sponsor: Seagen Inc.

New P1 trial • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

SGN-PDL1V, a novel, investigational PD-L1-directed antibody-drug conjugate for the treatment of solid tumors (SITC 2021) - "The vedotin drug-linker, consists of the microtubule disrupting agent, monomethyl auristatin E (MMAE), and a protease-cleavable peptide linker, which has been clinically validated in multiple ADC programs including brentuximab vedotin, enfortumab vedotin and polatuzumab vedotin.1–3 The proposed SGN-PDL1V primary mechanism of action is direct cytotoxicity against PD-L1-expressing malignant cells through delivery of the MMAE payload. Collectively, these data support further evaluation of SGN-PDL1V in a planned, first-in-human Phase 1 study. Trial Registration N/A"

IO biomarker • Oncology • Solid Tumor

Seagen to Highlight Two Novel Antibody-Drug Conjugates (ADCs) at the SITC 36th Annual Meeting - (Businesswire) - "Seagen Inc...announced the presentation of two new vedotin-based antibody-drug conjugate (ADC) programs at the Society for Immunotherapy of Cancer (SITC) 36th Anniversary Annual Meeting, taking place in Washington, D.C. and virtually, November 10-14, 2021. Each program combines antibodies targeted to an immune checkpoint [PD-(L)1 or B7-H4] with the cytotoxic properties of the vedotin payload. Preclinical data demonstrate promising antitumor activity. Both ADCs are set to enter first-in-human phase 1 studies in 2022."

Clinical data • New P1 trial • Preclinical • Oncology • Solid Tumor