Trial: A Study of SGN-PDL1V in Advanced Solid …

Trial Details

Sponsor: Seagen Inc. (industry)

Phase: 1

Start date: Oct. 25, 2022

Planned enrollment: 315

Trial ID: NCT05208762

More trial details at ClinicalTrials.gov

Show Summary from Sponsor

Investigational Drug AI Analysis

Show for: PF-08046054 (SGN-PDL1V)

Overview

PF-08046054, also known as SGN-PDL1V, is an investigational antibody-drug conjugate (ADC) targeting PD-L1, developed for the treatment of advanced solid tumors, including non-small cell lung cancer (NSCLC), gastric cancer, ovarian cancer, melanoma, head and neck squamous cell carcinoma (HNSCC), triple-negative breast cancer (TNBC), and esophageal squamous cell carcinoma (SCC). (pharmaceutical-technology.com)

Mechanism of Action

SGN-PDL1V comprises a PD-L1-directed antibody linked to monomethyl auristatin E (MMAE), a potent microtubule-disrupting agent. Upon binding to PD-L1-expressing tumor cells, the ADC is internalized, releasing MMAE intracellularly. This process induces direct cytotoxicity, a bystander effect, and immunogenic cell death, collectively enhancing antitumor activity. (ascopubs.org)

Efficacy

Interim results from a Phase I study presented at the European Society for Medical Oncology (ESMO) Congress 2024 indicated that SGN-PDL1V demonstrated preliminary antitumor activity. Among 55 patients with PD-L1-expressing solid tumors, the investigator-assessed objective response rate (ORR) was 27.3%, with a confirmed ORR of 12.7%. The median duration of confirmed responses was 7.9 months. Responses were observed starting at doses of 1.25 mg/kg and were independent of PD-L1 expression levels. (oncologypro.esmo.org)

Safety

In the same Phase I study, SGN-PDL1V was generally well tolerated. Common treatment-related adverse events (TRAEs) included peripheral sensory neuropathy (21.8%), asthenia (18.2%), fatigue (18.2%), and nausea (18.2%), primarily of grade 1-2 severity. Grade ≥3 TRAEs occurred in 30.9% of patients, with decreased neutrophil count being the most common (7.3%). No dose-limiting toxicities or immune-related TRAEs were reported. Treatment discontinuation due to adverse events was observed in 14.5% of patients. (oncologypro.esmo.org)

HealthScout AI Analysis

Goal: The goal of the trial is to assess the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of the investigational drug PF-08046054 (SGN-PDL1V), both as monotherapy and in combination with pembrolizumab, in patients with advanced solid tumors.

Patients: The trial is enrolling adults with metastatic or unresectable solid tumors who have relapsed or refractory disease after standard therapies, or who are unable to receive or have refused such therapies. Tumor types include non-small cell lung cancer, head and neck squamous cell carcinoma, esophageal squamous cell carcinoma, triple negative breast cancer, ovarian cancer, melanoma, and gastric cancer, with documented PD-L1 expression.

Design: This is a non-randomized, multi-part phase 1 trial comprising dose escalation and dose expansion cohorts. Patients receive either PF-08046054 monotherapy to establish safety and dosing, or a combination of PF-08046054 and pembrolizumab to evaluate safety and preliminary efficacy in selected tumor types.

Treatments: The study is evaluating PF-08046054 (SGN-PDL1V), a novel investigational antibody-drug conjugate that targets PD-L1 and delivers the cytotoxic payload monomethyl auristatin E (MMAE) to PD-L1-expressing tumor cells. The agent is designed for direct cell killing, bystander effect, and potential immunogenic cell death, with an antibody engineered to reduce immune-related adverse events. Interim phase 1 results showed objective responses (ORR 27.3%, 12.7% confirmed) and a manageable safety profile, mostly grade 1-2 adverse events, and no dose-limiting toxicities. The trial also includes combination therapy with pembrolizumab, a PD-1 inhibitor, to assess additive or synergistic efficacy and safety.

Outcomes: Primary outcomes are safety and tolerability parameters, including rates of adverse events, laboratory abnormalities, and dose-limiting toxicities. Secondary outcomes include pharmacokinetic measures (AUC, Cmax, and Ctrough), confirmed objective response rate per RECIST v1.1, duration of response, progression-free survival, overall survival, and the incidence of anti-drug antibodies.

Burden on patient: The burden on patients is expected to be moderate to high, typical of phase 1 oncology studies. Participants will undergo frequent clinic visits for safety assessments, multiple pharmacokinetic blood samples, and disease response evaluations via imaging. The investigational nature of the therapy and combination arm may also require additional laboratory and immune monitoring. This level of monitoring and testing exceeds standard of care, reflecting the need for comprehensive safety and pharmacokinetic characterization in early phase trials.

Eligibility

Show Criteria

Inclusion Criteria:

* Parts A and B:

* Participants must have one of the following histologically- or cytologically-confirmed metastatic or unresectable solid tumor types

* Non-small cell lung cancer (NSCLC)

* Head and neck squamous cell carcinoma (HNSCC) (except nasopharyngeal cancer)

* Esophageal squamous cell carcinoma (SCC)

* Triple negative breast cancer (TNBC)

* Participants must have disease that is relapsed or refractory, that has progressed on approved therapies, be intolerant to or refused such therapies, or such and therapies are contraindicated and in the judgement of the investigator, should have no appropriate SoC therapeutic option

* Participants must have PD-L1 expression based on historical testing

* Part C:

* Participants must have disease that is relapsed or refractory or be intolerant to SoC therapies and must have one of the following tumor types

* HNSCC

* Participants with HNSCC must have histologically or cytologically-confirmed HNSCC

* NSCLC

* Participants must have histologically or cytologically-confirmed NSCLC. Participants with SCC and non--SCC histology are eligible. Note: Participants with a neuroendocrine component or histology are not eligible.

* Esophageal SCC

* Ovarian cancer

* Melanoma

* TNBC

* Gastric cancer

* Participants must have been previously tested for PD-L1 expression and should have PD-L1 expression ≥1 or \<1 by CPS or TPS based on historical testing

* Part D and Part E:

* Participants must have histologically or cytologically-confirmed disease of the HNSCC or NSCLC

* Participants must have PD-L1 expression based on historical testing

* Participants with NSCLC; PD-L1 expression ≥ 1% by TPS

* Participants with HNSCC; PD--L1 expression ≥1 by CPS

* Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1

* Measurable disease per RECIST v1.1 at baseline

Exclusion Criteria:

* History of another malignancy within 3 years of first dose of study treatment or any evidence of residual disease from a previously diagnosed malignancy.

* Known active central nervous system metastases. Participants with previously-treated brain metastases may participate provided they:

* Are clinically stable for at least 4 weeks prior to study entry after brain metastasis treatment

* Have no new or enlarging brain metastases

* And are off of corticosteroids prescribed for symptoms associate with brain metastases for at least 7 days prior to first dose of study treatment

* Lepto-meningeal disease

* Prior treatment with an anti-PD-L1 agent within less than 5 half-lives. This duration of time will vary according to the half-life of the specific agent.

* Previous receipt of an monomethylauristatin E (MMAE)-containing agent.

* Pre-existing neuropathy ≥Grade 2 per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0.

Trial Details

Show Summary from Sponsor

Investigational Drug AI Analysis

Show for: PF-08046054 (SGN-PDL1V)

Overview

Mechanism of Action

Efficacy

Safety

Further Reading

HealthScout AI Analysis

Eligibility

Show Criteria

Sites (47)

Institut Jules Bordet

University Health Network, Princess Margaret Hospital

McGill University Health Centre

Beijing Cancer Hospital

Beijing Friendship Hospital, Capital Medical University

Union Hospital Tongji Medical College Huazhong University of Science and Technology

Shanghai East Hospital

Gustave Roussy Institute - Service pharmacie

Institut Curie

Clinique Ambroise Pare

Hôpital Saint André - CHU Bordeaux

lnstitut Curie Pharmacy

Apotheke-Zytostatika Studien Charite- Universitatsmedizin Berlin Campus Virchow Klinkum

Charite Universitatsmedizin Berlin

Divisione di Sviluppo di Nuovi Farmaci per Terapie Innovative lstituto Europeo di Oncologia

Centro Ricerche Cliniche di Verona s.r.l. c/o Policlinico G.B Rossi

Azienda Ospedaliera Universitaria Integrata Verona - Policlinico G.B Rossi

UOC Oncologia - IRCCS Azienda Ospedaliero Universitaria Bologna

National Cancer Center Hospital East

Shizuoka Cancer Center

The Netherlands Cancer Institute

Hospital Duran I Reynals-Institut Català d'Oncologia L'Hospitalet (ICO L'Hospitalet)

CETIR Viladomat

Hospital Universitari Vall d'Hebron

START Madrid - CIOCC - Hospital Universitario HM Sanchinarro

Hospital Quiron Salud Barcelona

NEXT Oncology Barcelona - IOB - Hospital Quironsalud Barcelona

The Harley Street Clinic (THSC)

Diagnostic Centre

Royal Marsden Hospital

Pharmacy: Royal Marsden Hospital

Sarah Cannon Research Institute

Radiology

University of Alabama at Birmingham

University of Alabama at Birmingham

University of Alabama at Birmingham, IDS Pharmacy

University of California, Davis Medical Center

University of California Davis Comprehensive Cancer Center

University of Iowa Hospitals & Clinics

Karmanos Cancer Institute

Karmanos Cancer Institute

University Hospitals Cleveland Medical Center

The University of Texas MD Anderson Cancer Center Investigational Pharmacy Services

The University of Texas MD Anderson Cancer Center

South Texas Accelerated Research Therapeutics, LLC

START Mountain Region

NEXT Virginia