Abstract
956P Encouraging antitumor activity of PDL1V (PF-08046054) monotherapy, an ADC targeting PD-L1, correlates with antigen expression in patients with NSCLC
Annals of oncology, Vol.36(Suppl 2), pp.S625-S626
09/2025
DOI: 10.1016/j.annonc.2025.08.1525
Abstract
Background
PDL1V (PF-08046054) is an investigational ADC targeting PD-L1 comprised of MMAE conjugated to an effector-null antibody. Preliminary evidence of activity has been presented in patients (pts) with NSCLC; here we update response data by level of PDL1 expression.
Methods
Ph 1 study (C5851001; NCT05208762) of PDL1V enrolled pts with relapsed/refractory (2L+) NSCLC. Pts who received PDL1V at the recommended expansion dose of 1.5 mg/kg on Days 1 and 8 of a 21-day cycle using adjusted ideal body weight were included in the efficacy analysis. Pts were required to have measurable disease per RECIST v1.1 and ECOG PS ≤1. Safety data were pooled across all pts treated in the Ph 1 study at the recommended expansion dose.
Results
As of April 10, 2025, 45 pts with 2L+ NSCLC received PDL1V. The median age was 62.0 years (range 39-79); 44.4% were male, 66.7% had ECOG PS 1, 28.9% had squamous histology, and 31.1% had TPS <1% tumors (PD-L1 negative). The median number of prior lines of therapy was 2.0 (1, 8). The investigator-assessed cORR for all pts included was 22.2%, while the cORR was 32.3% for pts with TPS ≥1% tumors and 0% for those with TPS <1%. Within the PD-L1 positive group, the cORR for pts with TPS 1-49% tumors (n=15) was 26.7% and 37.5% for those with TPS ≥ 50% (n=16). Objective responses were observed in pts with PD-L1 expressing squamous (n=8) and non-squamous (n=23) tumors (37.5% and 30.4% cORR, respectively). Among all pts treated in the Ph 1 trial at the recommended expansion dose (N=95), peripheral sensory neuropathy (29.5%), nausea (27.4%), fatigue (25.3%), and diarrhea (22.1%) were the most common treatment-related adverse events (TRAEs); the majority were grade 1-2 in severity and 6.3% discontinued therapy due to TRAEs. The most common grade ≥ 3 TRAEs were anemia and neutrophil count decreased (4.2% each). The incidence of treatment-related immune-mediated adverse events was 11.6%; 3.2% were grade 3, with no grade 4 or 5.
Conclusions
PDL1V monotherapy is well tolerated with a manageable safety profile. Encouraging antitumor activity in 2L+ PD-L1 positive NSCLC was observed across a range of PDL1 expression and histology. These data support the design of the planned Ph 3 trial.
Details
- Title: Subtitle
- 956P Encouraging antitumor activity of PDL1V (PF-08046054) monotherapy, an ADC targeting PD-L1, correlates with antigen expression in patients with NSCLC
- Creators
- M. Oliva Bernal - Institut Català d'OncologiaA. Dowlati - University Hospitals Seidman Cancer CenterA. Desai - University of AlabamaN. Kotecki - Institut Jules BordetR. Saleh - McGill University Health CentreA. Sukari - Wayne State UniversityK. Burkitt - Cleveland ClinicN. Steeghs - The Netherlands Cancer InstituteE. Garralda - Vall d'Hebron Institute of OncologyA. Zivi - Azienda Ospedaliera Universitaria Integrata VeronaD. Laux - Division of Hematology, Oncology and Blood & Marrow Transplantation, University of Iowa Hospitals and Clinics, Iowa City, IA, United States of AmericaM. Gillison - The University of Texas MD Anderson Cancer CenterA. Patnaik - South Texas Accelerated Research TherapeuticsA.R. Minchom - NIHR Biomedical Research Centre at The Royal Marsden and the ICRS. Ochsenreither - Charité - Universitätsmedizin BerlinK. Ouali - Drug Development Department (DITEP), Gustave Roussy, Villejuif, FranceC. Le Tourneau - Institut CurieS. Gupta - PfizerR. Zhang - PfizerE. Fontana - Sarah Cannon Research Institute
- Resource Type
- Abstract
- Publication Details
- Annals of oncology, Vol.36(Suppl 2), pp.S625-S626
- DOI
- 10.1016/j.annonc.2025.08.1525
- ISSN
- 0923-7534
- eISSN
- 1569-8041
- Publisher
- Elsevier Ltd
- Grant note
- Seagen Inc.
This study was sponsored by Seagen Inc., which was acquired by Pfizer Inc. in December 2023.
- Language
- English
- Date published
- 09/2025
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9985035032602771
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