felmetatug vedotin (PF-08046048) / Pfizer - LARVOL DELTA

SGNB7H4V-001: A Study of Felmetatug Vedotin/SGN-B7H4V in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=246 | Terminated | Sponsor: Seagen, a wholly owned subsidiary of Pfizer | Trial completion date: Dec 2025 ➔ May 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: Dec 2025 ➔ May 2025; The trial was terminated for strategic reasons. The decision was not based on any safety and/or efficacy concerns

Trial completion date • Trial primary completion date • Trial termination • Adenoid Cystic Carcinoma • Biliary Cancer • Breast Cancer • Cholangiocarcinoma • Endometrial Cancer • Fallopian Tube Cancer • Gallbladder 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 • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • HER-2

SGNB7H4V-001: A Study of Felmetatug Vedotin/SGN-B7H4V in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=236 | Active, not recruiting | Sponsor: Seagen, a wholly owned subsidiary of Pfizer | N=572 ➔ 236 | Trial completion date: Nov 2027 ➔ Dec 2025 | Trial primary completion date: Nov 2027 ➔ Dec 2025

Enrollment change • Trial completion date • Trial primary completion date • Adenoid Cystic Carcinoma • Biliary Cancer • Breast Cancer • Cholangiocarcinoma • Endometrial Cancer • Fallopian Tube Cancer • Gallbladder Cancer • Hepatology • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • HER-2

B7 Homolog 4 (B7-H4)-Directed Agents in Oncology Clinical Trials: A Review. (PubMed, J Immunother Precis Oncol) - "B7-H4-directed agents, particularly antibody-drug conjugates (ADCs) like puxitatug samrotecan (AZD8205), felmetatug vedotin (SGN-B7H4V), and GSK5733584, have demonstrated early clinical activity with promising response rates in triple-negative breast cancer (TNBC). Combination strategies, such as ADCs with anti-PD-1 or PARP inhibitor therapies, have also shown enhanced tumor regression in preclinical models and are the subject of several ongoing clinical trials. This review highlights the current landscape of B7-H4-targeted agents, their progress in clinical trials, and the potential for combination approaches to improve outcomes in B7-H4-expressing cancers."

Journal • Review • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • VTCN1

Pfizer axes B7-H4 ADC, triggering $1B impairment charge as blockbuster vision evaporates (FierceBiotech) - "Pfizer has ended development of a B7-H4-directed antibody-drug conjugate (ADC), triggering a $1 billion impairment charge....'We have made a business decision to discontinue the felmetatug vedotin (FV) development program based on clinical data generated to date indicating that FV is unlikely to achieve a meaningful improvement over standard-of-care chemotherapy in patients with advanced solid tumors, including triple-negative breast cancer'..."

Discontinued • Triple Negative Breast Cancer

SGNB7H4V-001: A Study of SGN-B7H4V in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=572 | Active, not recruiting | Sponsor: Seagen Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Adenoid Cystic Carcinoma • Biliary Cancer • Breast Cancer • Cholangiocarcinoma • Endometrial Cancer • Fallopian Tube Cancer • Gallbladder Cancer • Hepatology • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • HER-2

SGNB7H4V-001: A Study of SGN-B7H4V in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=572 | Recruiting | Sponsor: Seagen Inc. | N=430 ➔ 572 | Trial completion date: Jan 2027 ➔ Nov 2027 | Trial primary completion date: Jun 2025 ➔ Nov 2027

Enrollment change • Trial completion date • Trial primary completion date • Adenoid Cystic Carcinoma • Biliary Cancer • Breast Cancer • Cholangiocarcinoma • Endometrial Cancer • Fallopian Tube Cancer • Gallbladder Cancer • Hepatology • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • HER-2

First-in-human study of SGN-B7H4V, a B7-H4-directed vedotin ADC, in patients with advanced solid tumors: Preliminary results of a phase I study (SGNB7H4V-001) (ESMO 2023) - P1 | "Responses were observed at all tested dose levels and across various tumor types. Dose expansion in select tumor types is planned."

Clinical • Metastases • P1 data • Biliary Cancer • Biliary Tract Cancer • Endometrial Cancer • Gastrointestinal Cancer • Oncology • Ovarian Cancer • Solid Tumor • VTCN1

SGNB7H4V-001: A Study of SGN-B7H4V in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=400 | Recruiting | Sponsor: Seagen Inc. | Active, not recruiting ➔ Recruiting | N=164 ➔ 400

Enrollment change • Enrollment open • Metastases • Adenoid Cystic Carcinoma • Biliary Cancer • Breast Cancer • Cholangiocarcinoma • Endometrial Cancer • Fallopian Tube Cancer • Gallbladder Cancer • Gastrointestinal Cancer • Hepatology • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • HER-2

Seagen to Highlight Overall Survival Data for PADCEV and TIVDAK during Presidential Symposium at ESMO Congress 2023 (Seagen Press Release) - "Seagen Inc...announced the upcoming presentation of detailed results from two pivotal Phase 3 studies at the ESMO Congress 2023....Seagen will also present results from the innovaTV 301 study of TIVDAK (tisotumab vedotin-tftv) compared with chemotherapy in adults with recurrent or metastatic cervical cancer during the same Presidential Symposium. Both presentations are included in the ESMO Communication Activities. Seagen is sharing a total of six abstracts, including five oral presentations at ESMO this year, taking place October 20–24, 2023 in Madrid, Spain....Early clinical data from a Phase 1 study of SGN-B7H4V, a wholly owned vedotin ADC directed to B7-H4, will be shared at ESMO. B7-H4 is a member of the B7 family of immune checkpoint ligands and its expression is elevated on a variety of solid tumors, including breast, ovarian, and endometrial cancers."

P1 data • P3 data • Biliary Cancer • Biliary Tract Cancer • Breast Cancer • Cervical Cancer • Cholangiocarcinoma • Endometrial Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor

SGNB7H4V-001: A Study of SGN-B7H4V in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=164 | Active, not recruiting | Sponsor: Seagen Inc. | Recruiting ➔ Active, not recruiting | N=400 ➔ 164

Enrollment change • Enrollment closed • Metastases • Adenoid Cystic Carcinoma • Biliary Cancer • Breast Cancer • Cholangiocarcinoma • Endometrial Cancer • Fallopian Tube Cancer • Gallbladder Cancer • Gastrointestinal Cancer • Hepatology • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • HER-2

SGN-B7H4V, an investigational vedotin ADC directed to the immune checkpoint ligand B7-H4, shows promising activity in preclinical models (J Immunother Cancer) - "Immunohistochemistry confirmed B7-H4 expression across multiple solid tumors, with the highest prevalence in breast, endometrial, and ovarian tumors....In vivo, SGN-B7H4V demonstrated strong antitumor activity in multiple xenograft models of breast and ovarian cancer, including xenograft tumors with heterogeneous B7-H4 expression, consistent with the ability of vedotin ADCs to elicit a bystander effect."

Preclinical • Breast Cancer • Endometrial Cancer • Ovarian Cancer

SGN-B7H4V, an investigational vedotin ADC directed to the immune checkpoint ligand B7-H4, shows promising activity in preclinical models. (PubMed, J Immunother Cancer) - P1 | "The immune checkpoint ligand B7-H4 is a promising molecular target expressed by multiple solid tumors. SGN-B7H4V demonstrates robust antitumor activity in preclinical models through multiple potential mechanisms. Altogether, these preclinical data support the evaluation of SGN-B7H4V as a monotherapy in the ongoing phase 1 study of SGN-B7H4V in advanced solid tumors (NCT05194072) and potential future clinical combinations with immunotherapies."

IO biomarker • Journal • Preclinical • Endometrial Cancer • Oncology • Ovarian Cancer • Solid Tumor • VTCN1

A Study of SGN-B7H4V in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=355 | Recruiting | Sponsor: Seagen Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Biliary Cancer • Breast Cancer • Cholangiocarcinoma • Endometrial Cancer • Fallopian Tube Cancer • Gallbladder Cancer • Gastrointestinal Cancer • Hepatology • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • HER-2

SGN-B7H4V induces immunomodulatory changes to the tumor microenvironment and pairs well with an anti-PD1 agent in a preclinical model (SITC 2022) - P1 | "This vedotin drug linker system has been clinically validated in multiple ADC programs, including brentuximab vedotin, enfortumab vedotin, and tisotumab vedotin. Moreover, SGN-B7H4V in combination with an anti-PD1 agent led to improved antitumor activity and elicited durable immune memory. Altogether, these nonclinical data further support the evaluation of SGN-B7H4V as a monotherapy in the ongoing Phase 1 Study of SGN-B7H4V in Advanced Solid Tumors ( NCT05194072 ) and potential future clinical combinations with immunotherapies."

IO biomarker • Preclinical • Tumor microenvironment • Endometrial Cancer • Oncology • Ovarian Cancer • Solid Tumor • VTCN1

Phase 1 study of SGN-B7H4V, a novel, investigational vedotin antibody–drug conjugate directed to B7-H4, in patients with advanced solid tumors (SGNB7H4V-001, trial in progress). (ASCO 2022) - P1 | "DOR, PFS, and OS will be estimated using the Kaplan–Meier method. Enrollment for Part A is ongoing in North America and is planned in Europe."

Clinical • P1 data • Biliary Cancer • Breast Cancer • Cholangiocarcinoma • Endometrial Cancer • Fallopian Tube Cancer • Gallbladder Cancer • Gastrointestinal Cancer • Hepatology • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Immune Modulation • Inflammation • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • Squamous Cell Carcinoma • Triple Negative Breast Cancer • HER-2 • VTCN1

SGN-B7H4V Has Immunomodulatory Activity & Combines With Anti-PD1 Agents in Preclinical Models (ADC-USA 2022) - "SGN-B7H4V is an investigational vedotin ADC targeting the immune checkpoint ligand B7-H4 Understand how SGN-B7HAV elicits antitumor activity in vivo, accompanied by immune changes in the tumor microenvironment Assess how combination studies suggest SGN-B7H4V may pair well with an ant-PD-1 agent"

Preclinical • Immune Modulation • Inflammation • Oncology • VTCN1

SGN-B7H4V shows immunomodulatory activity through induction of immunogenic cell death (AACR 2022) - "This vedotin drug linker system has been clinically validated by multiple ADC programs, including brentuximab vedotin, enfortumab vedotin, tisotumab vedotin, and polatuzumab vedotin. Finally, SGN-B7H4V drove robust, curative activity in an immunocompetent tumor model as a monotherapy and paired well with an anti-PD1 agent. Altogether, these data support the evaluation of SGN-B7H4V as a monotherapy in a first-in-human phase 1 clinical study and potential future clinical combinations with immunotherapies."

Immunogenic cell death • IO biomarker • Endometrial Cancer • Oncology • Ovarian Cancer • Solid Tumor • CALR • VTCN1

Seagen to Highlight Preclinical Data for Enfortumab Vedotin and Two Novel Antibody-Drug Conjugates at AACR Annual Meeting 04/08/2022 (Seagen Press Release) - "In preclinical studies, SGN-ALPV exhibited robust antitumor activity in cell line and patient-derived xenograft cancer models with both homogenous and heterogeneous expression of placental alkaline phosphatases ALPP and ALPPL2, consistent with robust monomethyl auristatin E (MMAE)-directed cytotoxicity and bystander activity of vedotin ADCs....SGN-B7H4V shows immunomodulatory activity through induction of immunogenic cell death."

Preclinical • Oncology

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-B7H4V in Advanced Solid Tumors (clinicaltrials.gov) - P1; N=355; Not yet recruiting; Sponsor: Seagen Inc.

New P1 trial • Biliary Cancer • Breast Cancer • Cholangiocarcinoma • Endometrial Cancer • Fallopian Tube Cancer • Gallbladder Cancer • Gastrointestinal Cancer • Hepatology • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • HER-2

SGN-B7H4V, a novel, investigational vedotin antibody-drug conjugate directed to the T cell checkpoint ligand B7-H4, shows promising activity in preclinical models (SITC 2021) - "This ”vedotin” drug linker system has been clinically validated by multiple ADC programs, including brentuximab vedotin, enfortumab vedotin, and polatuzumab vedotin.2–4 Here, we characterize the target antigen B7-H4 and evaluate SGN-B7H4V activity in preclinical models. SGN-B7H4V demonstrates robust anti-tumor activity in preclinical models through multiple potential mechanisms and is tolerated in rat and NHP toxicity studies. Altogether, these data support further evaluation of SGN-B7H4V in a planned, first-in-human phase 1 clinical study."

Preclinical • Breast Cancer • Endometrial Cancer • Oncology • Ovarian Cancer • Solid Tumor • VTCN1

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