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 (SGN-PDL1V) is an investigational vedotin antibody–drug conjugate (ADC) that targets PD-L1 and delivers the cytotoxic payload monomethyl auristatin E (MMAE). It is being evaluated in an ongoing first‑in‑human, multi‑part phase 1 study (NCT05208762) in advanced solid tumors as monotherapy and in combination with pembrolizumab. (pfizeroncologydevelopment.com)

Mechanism of action

Target: PD-L1 on tumor cells. The ADC uses an engineered anti–PD‑L1 antibody designed for increased internalization to enhance payload delivery. (pfizeroncologydevelopment.com)
Payload/linker: MMAE via a protease‑cleavable vedotin linker. (pfizeroncologydevelopment.com)
Proposed antitumor mechanisms: direct MMAE‑mediated cytotoxicity of PD‑L1–expressing tumor cells, a bystander effect enabling killing of neighboring cells, and induction of immunogenic cell death (ICD). Preclinical work presented at SITC 2021 supported these mechanisms. (ascopubs.org)

Efficacy

Interim phase 1 monotherapy results reported at ESMO 2024 (data cutoff March 6, 2024; n=55 across dose levels 0.5–1.75 mg/kg, Q3W D1/8) showed: - Investigator‑assessed objective response rate (ORR): 27.3% across tumor types and doses; confirmed ORR 12.7%.
- Median duration of confirmed responses: 7.9 months.
- Responses observed starting at 1.25 mg/kg and reported as independent of PD‑L1 expression. (oncologypro.esmo.org)

The ongoing trial includes disease‑specific expansion cohorts and planned combination cohorts with pembrolizumab. Additional readouts are expected as enrollment and follow‑up mature. (ascopubs.org)

Safety

In the same ESMO 2024 interim analysis (n=55): - No dose‑limiting toxicities were observed; 1.75 mg/kg was the highest dose evaluated.
- Most common treatment‑related adverse events (TRAEs): peripheral sensory neuropathy (21.8%), asthenia (18.2%), fatigue (18.2%), nausea (18.2%); largely grade 1–2.
- Grade ≥3 TRAEs: 30.9%; most common was decreased neutrophil count (7.3%).
- No immune‑related TRAEs were reported.
- Treatment discontinuation due to treatment‑emergent AEs occurred in 14.5% of patients. (oncologypro.esmo.org)

HealthScout AI Analysis

Goal: Evaluate the safety, tolerability, dose range, and preliminary antitumor activity of the PD-L1–directed antibody-drug conjugate PF-08046054 (SGN-PDL1V) as monotherapy and in combination with pembrolizumab in participants with advanced solid tumors. Define dose-limiting toxicities, characterize pharmacokinetics and immunogenicity, and estimate early efficacy signals to inform future development.

Patients: Adults with metastatic or unresectable solid tumors and ECOG 0–1 with measurable disease per RECIST v1.1. Parts A/B enroll relapsed/refractory NSCLC, HNSCC (non-nasopharyngeal), esophageal SCC, or TNBC with historical PD-L1 testing and no appropriate standard-of-care options. Part C expands to additional tumor types (HNSCC, NSCLC excluding neuroendocrine histology, esophageal SCC, ovarian cancer, melanoma, TNBC, gastric cancer) with historical PD-L1 testing (CPS or TPS ≥1 or <1). Parts D/E enroll HNSCC or NSCLC with PD-L1 expression; NSCLC requires TPS ≥1% and HNSCC requires CPS ≥1. Key exclusions include active CNS metastases (unless controlled), leptomeningeal disease, prior anti–PD-L1 within fewer than five half-lives, prior exposure to MMAE-containing agents, and pre-existing grade ≥2 neuropathy.

Design: Phase 1, multicenter, nonrandomized, multi-part dose-escalation and dose-expansion study. Parts A/B define the recommended dose for monotherapy; Part C evaluates safety and activity at the selected dose across tumor cohorts; Parts D/E assess the safety and activity of PF-08046054 in combination with pembrolizumab. Planned enrollment approximately 315 participants.

Treatments: PF-08046054 (SGN-PDL1V) monotherapy; PF-08046054 plus pembrolizumab. PF-08046054 is a PD-L1–targeted antibody-drug conjugate composed of a PD-L1 monoclonal antibody linked via a protease-cleavable linker to the microtubule-disrupting payload monomethyl auristatin E (MMAE). It is designed for direct cytotoxic delivery to PD-L1–expressing tumor cells with potential bystander effect and immunogenic cell death; the antibody is engineered to minimize complement and Fc-mediated immune effector functions. Interim Phase 1 data in a mixed solid tumor population across 0.5–1.75 mg/kg showed an overall response rate of approximately 27% (about 13% confirmed) with responses emerging at ≥1.25 mg/kg and appearing independent of PD-L1 level; safety was manageable with predominantly grade 1–2 neuropathy, asthenia/fatigue, and nausea, and no reported immune-related AEs; grade ≥3 TRAEs occurred in about 31% with neutropenia the most common high-grade event. Pembrolizumab is a standard anti–PD-1 antibody used broadly in PD-L1–expressing tumors.

Outcomes: Primary: safety and tolerability including adverse events, laboratory abnormalities, and dose-limiting toxicities overall and by dose level. Secondary: pharmacokinetics (AUC, Cmax, trough), confirmed objective response rate by RECIST v1.1, duration of response, progression-free survival, overall survival, and incidence of anti-drug antibodies. Assessments continue through approximately 3 years with safety follow-up up to ~90 days after last dose and PK/immunogenicity sampling up to ~30–37 days after last dose.

Burden on patient: High. As an early-phase, multi-part study with dose escalation and combination cohorts, participants should expect frequent on-site visits, intensive safety monitoring, serial PK and immunogenicity blood draws, and repeated imaging per RECIST. Tumor biopsies may be required in some parts, and historical PD-L1 testing is necessary; fresh biopsies could be requested in expansions. The ADC carries risks of neuropathy and myelosuppression necessitating neurological exams and laboratory monitoring. Combination cohorts add immune checkpoint therapy–related monitoring. Overall, visit frequency and procedures exceed standard-of-care for metastatic patients, with travel and time commitments over many months if deriving benefit.

Last updated: Oct 2025

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 (56)

Institut Jules Bordet

University Health Network, Princess Margaret Hospital

McGill University Health Centre

Beijing Friendship Hospital, Capital Medical University

Beijing Cancer Hospital

Union Hospital Tongji Medical College Huazhong University of Science and Technology

Shanghai East Hospital

Hôpital Saint André - CHU Bordeaux

Gustave Roussy Institute - Service pharmacie

Institut Curie

lnstitut Curie Pharmacy

Clinique Ambroise Pare

Charite Comprehensive Cancer Center

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

START Madrid - CIOCC - Hospital Universitario HM Sanchinarro

Hospital Quiron Salud Barcelona

NEXT Oncology Barcelona - IOB - Hospital Quironsalud Barcelona

Hospital Universitari Vall d'Hebron

The Harley Street Clinic (THSC)

Diagnostic Centre

Royal Marsden Hospital

Pharmacy: Royal Marsden Hospital

Radiology

Sarah Cannon Research Institute

The Royal Marsden NHS Foundation Trust

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

South Texas Accelerated Research Therapeutics, LLC

The University of Texas MD Anderson Cancer Center

The University of Texas MD Anderson Cancer Center Investigational Pharmacy Services

UT Southwestern - Simmons Cancer Center - Fort Worth

University Of Texas Southwestern Medical Center

University of Texas Southwestern Medical Center - William P. Clements, Jr., University Hospital

Univ. of TX Southwestern Medical Center - Zale Lipshy University Hospital

UT Southwestern Medical Center - Redbird

University of Texas Southwestern Medical Center - Simmons Cancer Center

UT Southwestern - Simmons Cancer Center - Richardson/Plano

START Mountain Region

NEXT Virginia