607O - Interim results of a phase I study of SGN-PDL1V (PF-08046054) in patients with PDL1-expressing solid tumors

Background

To assess the safety/tolerability and antitumor activity of SGN-PDL1V, a novel investigational antibody-drug conjugate that delivers monomethyl auristatin E to cells that express Programmed Cell Death Ligand 1 (PDL1).

Methods

SGNPDL1V-001 (NCT05208762) is a phase 1 study enrolling patients (pts) with relapsed/refractory PDL1-expressing solid tumors (non-small cell lung cancer [NSCLC], head and neck squamous cell carcinoma [HNSCC], triple negative breast cancer [TNBC], and esophageal cancer [EC]) who progressed on standard of care therapies. Measurable disease per RECIST v1.1, and ECOG PS of ≤1 are required. In dose escalation, pts received doses of SGN-PDL1V from 0.5-1.75 mg/kg on days 1, and 8 of every 21-day cycle using adjusted ideal body weight. The primary objectives of this study are safety/tolerability and pharmacokinetics with antitumor activity as a secondary objective.

Results

As of March 6, 2024, 55 pts were dosed with a median age of 60 years (range 24–72); 54.5% were male, 72.7% had ECOG PS 1, 54.5% had HNSCC, 29.1% NSCLC, 14.5% TNBC, and 1.8% EC. No dose-limiting toxicities (DLTs) were seen; 1.75 mg/kg was the highest dose evaluated. Peripheral sensory neuropathy (21.8%), asthenia (18.2%), fatigue (18.2%), and nausea (18.2%), were the most common treatment-related adverse events (TRAEs); the majority were grade 1-2 in severity. No immune-related TRAEs were seen. Overall grade ≥ 3 TRAEs was 30.9%. The most common grade ≥ 3 TRAE was decreased neutrophil count (7.3%). Treatment discontinuation due to treatment-emergent AEs was seen in 14.5% of pts. The investigator-assessed objective response rate (ORR) across all doses and tumor types was 27.3% (12.7% confirmed), and the median duration of confirmed responses was 7.9 months. Objective responses were observed starting at 1.25 mg/kg and independent of PDL1 expression.

Conclusions

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 trial identification

NCT05208762.

Editorial acknowledgement

Editorial support was provided by Haniya Javaid of Engage Scientific Solutions.

Legal entity responsible for the study

Seagen, which was acquired by Pfizer in 2023.

Funding

This study was sponsored by Seagen Inc., which was acquired by Pfizer in December 2023.

Disclosure

M. Oliva: Financial Interests, Personal, Advisory Board: Merck, MSD; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Invited Speaker, Teaching Activities: Merck, MSD; Financial Interests, Personal, Writing Engagement: MSD; Financial Interests, Personal, Other, IDMC: Transgene; Non-Financial Interests, Institutional, Local PI: AbbVie, ALX Oncology, Ayala Therapeutics, Bayer, BeiGene, Boehringer Ingelheim, Debiopharm, Gilead, ISA Therapeutics BV, Merck, MSD, Nykode, Seagen; Non-Financial Interests, Institutional, Funding: GSK; Financial Interests, Institutional, Local PI: Roche; Non-Financial Interests, Personal, Funding: Roche; Financial Interests, Product Samples: Roche. C. Le Tourneau: Consulting: MSD, BMS, Merck Serono, ALX Oncology, Seatle Genetics, Roche, Nanobiotix, MaxiVax, Exscientia, Seagen, Merus, Immutep, Kumar Therapeutics, PCI Biotech, Onxeo. A. Spreafico: Study funding: PFE. A.R. Minchom: Advisory boards: Janssen Pharmaceuticals, Merck Pharmaceuticals, Takeda Pharmaceuticals, MSD Pharmaceuticals, Genmab Pharmaceuticals and Immutep Pharmaceuticals; Honoraria: Chugai Pharmaceuticals, Faron Pharmaceuticals, Merck Pharmaceuticals, GSK, Seagen and Janssen Pharmaceuticals; Travel support: Amgen Pharmaceuticals and Janssen Pharmaceuticals; Research funding: Astex Pharmaceutical, Merck Pharmaceuticals and MSD. A. Patnaik: Financial Interests, Institutional research funding: Compugen. E. Fontana: Financial Interests, Personal, Invited Speaker: Caris Life Science, Repair Therapeutics; Financial Interests, Personal, Conference attendance: Sapience Pharma; Financial Interests, Personal, Invited Speaker, Conference Attendance: Bicycles Therapeutics; Financial Interests, Personal, Full or part-time Employment: Hospital Corporation of America (HCA) International; Financial Interests, Personal Officer: EORTC; Financial Interests, Institutional, Local PI: Bicycle Therapeutics, Artios Pharma, Seagen, Nurix Therapeutics, BioNTech SE, Relay Therapeutics, Pfizer, Roche, Daiichi Sankyo, Gilead Science, Basilea Pharmaceutica, Jiangsu Hengrui Medicine, Mereo Biopharma, Hutchmed, Merus, Crescendo Biologics, GSK Plc, BeiGene, Turning Point Therapeutics, Sapience Pharma, Arcus Bioscience, Exelixis, Nerviano Medica, Elipsees, Deciphera, Ribon Therapeutics; Financial Interests, Coordinating PI, Institutional: Repair Therapeutics, Amgen, Taiho Pharmaceutical. E. Garralda: Financial Interests, Personal, Invited Speaker: MSD, Roche, Thermo Fisher, Novartis, SeaGen; Financial Interests, Personal, Advisory Board: Roche, Ellipses Pharma, Boehringer Ingelheim, Janssen Global Services, Seattle Genetics, Thermo Fisher, MabDiscovery, Anaveon, Hengrui, F-Star Therapeutics, Sanofi, Incyte, Medscape; Financial Interests, Personal, Full or part-time Employment: Next Oncology; Financial Interests, Personal, Stocks/Shares: 1TRIALSP; Financial Interests, Institutional, Funding: Novartis, Roche, Thermo Fisher, AstraZeneca, Taiho; Financial Interests, Institutional, Research Grant: BeiGene, Janssen. J.W. Riess: Financial Interests, Personal, Advisory Board: Biodesix, Merus, Bayer, Regeneron, Sanofi, Seattle Genetics, BMS, Daiichi Sankyo, Roche/Genentech, Janssen, Amgen, Catalyst; Financial Interests, Personal, Consulting fees: EMD Serono, Novartis; Financial Interests, Institutional, Steering Committee Member: AstraZeneca; Financial Interests, Institutional, Local PI: ArriVent, Revolution Medicines, Seattle Genetics, Nuvalent, Kinnate; Financial Interests, Personal, Trial Chair: Merck; Financial Interests, Institutional, Trial Chair: Novartis; Financial Interests, Institutional, Coordinating PI: Summit, IO Biotech. S. Gupta, R. Zhang: Other, Institutional, Full or part-time Employment: Pfizer. M. Gillison: Consulting: Debiopharm, Sensei Biotherapeutics, Inc., iTeos Therapeutics, Caladrius Biosciences, Exelixis Inc., GSK Llc, Merus N.V., EMD Serono, Gilead Sciences, Kura Oncology, Shattuck Labs, Eisai Medical Research, Istari Oncology, LLX Solutions, Mirati Therapeutics, Caladrius Biosciences, Nektar Therapeutics, Pilant Therapeutics, Onclive, Bicara Therapeutics, Ispen BioPharmaceuticals, Coherus Biosciences, Surface Oncology, Bristol Myers Squibb, BioNTech, Aptitude Health, AH EPICS Consulting, Axiom Healthcare, Adaptimmune, Guidepoint Global, Brightly Network, Pfizer, AbbVie; Editorial role: Journal of Clinical Oncology; Research Funding to Genocea Biosciences, Inc., Bristol Myers Squibb, Genentech, Kura, Cullinan Labs, Agenus, LaRoche, NRG, University of Cincinnati. All other authors have declared no conflicts of interest.