Abstract 1189TiP
Background
Despite intrinsic resistance to PD-(L)1 immunotherapy (immunoTx), some NSCLCs are susceptible to T-cell–mediated antitumor effects. Targeting cancer immunity pathways may enhance response in relapsed or refractory NSCLC. The CD226 Axis includes the T- and NK-cell inhibitory receptors TIGIT, CD96, and PVRIG; the T/NK-cell–activating receptor CD226; and cognate ligands CD155 and CD112. This multifaceted group of immune receptors plays a critical role in regulating antitumor responses. The immune checkpoints TIGIT, CD96, and PVRIG may prevent CD226 from interacting with CD155 and CD112, directly impairing NK- and T-cell function, which may reduce antitumor activity. GSK’859A/EOS-448 and GSK’608 are high-affinity anti-TIGIT and anti-CD96 monoclonal antibodies (mAbs), respectively. They inhibit the immunosuppressive activity of TIGIT and CD96 and allow ligands CD155 and CD112 to bind the costimulatory receptor CD226. Preliminary phase I/II GSK’859A/EOS-448 (NCT05060432) data suggest a manageable safety profile and early signs of clinical activity, including in heavily treated solid tumors refractory to PD-(L)1 inhibition. A phase I study of GSK’608 ± dostarlimab (anti–PD-1 mAb) is ongoing (NCT04446351). Here, we describe the part 1 design of the GSK’859A/EOS-448 + GSK’608 + dostarlimab combination arm of ENTRÉE, a phase II NSCLC platform study (NCT03739710) exploring multiple checkpoint inhibitor–based approaches to overcome immunoTx resistance.
Trial design
Methods: Adults (≥18 years) with ECOG PS 0-1 are eligible if they have histologically or cytologically confirmed NSCLC that progressed during or after ≤2 lines of systemic Tx for locally/regionally advanced stage IIIb/IIIc/IV or metastatic disease, including 1 line of platinum-containing chemoTx and 1 line of PD-(L)1 mAb Tx in the same or separate lines of Tx. Patients will receive IV GSK’859A/EOS-448 + dostarlimab + GSK’608 (dose escalation) q3w for ≤35 cycles or 2 years or until disease progression, consent withdrawal, intolerability, or death. Part 1 endpoints are safety and tolerability (primary) and efficacy and pharmacokinetics (secondary).
Clinical trial identification
NCT03739710.
Editorial acknowledgement
The authors thank the participating patients, families, investigators, site staff, and colleagues at GlaxoSmithKline (GSK) and iTeos Therapeutics. Funding for the study (study 205801) was provided by GSK and iTeos. Writing and editorial support was provided by Peter J. Simon of MediTech Media and funded by GSK and iTeos.
Legal entity responsible for the study
GlaxoSmithKline.
Funding
GlaxoSmithKline and iTeos Therapeutics.
Disclosure
D.R. Spigel: Financial Interests, Other, Consulting or Advisory Role: Genentech/Roche, Novartis, Bristol-Myers Squibb, AstraZeneca, Pfizer, GlaxoSmithKline; Financial Interests, Other, Consulting: EMD Serono, Molecular Templates, Amgen, Curio Sciences, Intellisphere, Jazz Pharmaceuticals, Mirati Therapeutics, Puma Biotechnology, Sanofi/Aventis, Exelixis, Regeneron, Lilly, Janssen, Evidera, BeiGene, Novocure; Financial Interests, Other, Research Funding: Genentech/Roche; Financial Interests, Other, Research: Novartis, Celgene, Bristol-Myers Squibb, Lilly, AstraZeneca, University of Texas Southwestern Medical Center - Simmons Cancer Center, Merck, G1 Therapeutics, Neon Therapeutics, Takeda, Nektar, Celldex, Clovis Oncology, Daiichi Sankyo, EMD Serono, Astellas Pharma, GRAIL, Transgene, Aeglea Biotherapeutics, Ipsen, BIND Therapeutics, Eisai, ImClone Systems, Immunogen, Janssen Oncology, MedImmune, Molecular Partners, Agios, GlaxoSmithKline, Tesaro, Cyteir Therapeutics, Apollomics, Novocure, Elevation Oncology, Calithera Biosciences, Arcus Biosciences, Arrys Therapeutics, Bayer, BeiGene, Blueprint Medicines, Boehringer Ingelheim, Denovo Biopharma, Hutchison MediPharma, Incyte, Kronos Bio, Loxo Oncology, MarcoGenics, Molecular Templates, Oncologie, Pfizer, PTC Therapeutics, Pure Tech Health, Razor Genomics, Repare Therapeutics, Rgenix, Tizona Therapeutics, Inc., Verastem, Evelo Biosciences, BioNTech; Financial Interests, Other, Travel, Accommodations, Expenses: AstraZeneca, Genentech, Novartis. P. Garrido Lopez: Financial Interests, Other, Employment: Teva; Financial Interests, Other, Travel, Accommodations, expenses: AstraZeneca, Roche. P.K. Cheema: Financial Interests, Other, Advisory board/honorarium: Amgen, AstraZeneca, Roche, BMS, Pfizer, BeiGene, Jansen, Merck, Bayer; Financial Interests, Other, Consultancy: Novartis, Roche, AstraZeneca. M.C. Garassino: Financial Interests, Personal and Institutional, Other: AstraZeneca, BMS, Boehringer Ingelheim Italia S.p.A, Celgene, Eli Lilly, Ignyta, Incyte, MedImmune, Novartis, Pfizer, Roche, Takeda; Financial Interests, Personal, Other: MSD International GmbH, Inivata, Seattle Genetics, Mirati, Daiichi Sankyo, Regerenon, Merck; Financial Interests, Institutional, Other: Tiziana, Foundation Medicine, GlaxoSmithKline, Spectrum Pharmaceuticals; Financial Interests, Other: AIRC, AIFA, Italian MoH, TRANSCAN, Research Findings. M. Reck: Financial Interests, Institutional, Invited Speaker, lectures and consultancy: Amgen, AstraZeneca, BMS, BeiGene, Boehringer Ingelheim, GlaxoSmithKline, Merck, MSD, Mirati, Lilly, Novartis, Pfizer, Roche, Sanofi. All other authors have declared no conflicts of interest.