945TiP - JADE: A phase (ph) III study to evaluate dostarlimab vs placebo (PBO) as sequential therapy after chemoradiation (CRT) in patients (pts) with locally advanced unresected head and neck squamous cell carcinoma (LA-HNSCC)

Background

LA-HNSCC treatment involves combined surgery and CRT; however, as <50% of pts are disease free at 2 years, new treatments are needed. Although anti-programmed cell death (ligand) protein 1 (anti–PD-[L]1) therapies are standard of care for pts with recurrent/metastatic HNSCC, recent ph3 studies in LA-HNSCC (KEYNOTE-412; IMvoke010) did not show improved outcomes for anti–PD-(L)1 therapy administered concurrently and sequentially to CRT vs PBO, or in an all-comers population after multimodal definitive treatment. In a post hoc analysis of KEYNOTE-412, pts with HNSCC with high PD-L1 expression had numerically improved outcomes vs pts with low/no expression. A recent ph2 study showed numerically improved outcomes for pts with LA-HNSCC who received the anti–PD-1 pembrolizumab sequential to CRT vs concurrently. JADE will evaluate the efficacy and safety of sequential dostarlimab vs PBO following CRT for pts with PD-L1+ LA-HNSCC.

Trial design

JADE is a global, randomised, double-blind, PBO-controlled ph3 study. Key eligibility includes: ≥18 years of age; newly diagnosed, unresected LA-HNSCC of the oral cavity, oropharynx, hypopharynx, or larynx; completed concurrent CRT with curative intent; no distant metastases and PD-L1+ (combined positive score [CPS] ≥1). 864 pts will be enrolled. Pts will be stratified by tumour site/p16 status (larynx/hypopharynx/oral cavity, and p16 negative/positive oropharynx), cisplatin schedule (high dose, every 3 weeks [Q3W] or low dose, Q1W), and PD-L1 status (CPS 1–19 or ≥20). Following CRT, pts will be randomised 1:1 to receive 500 mg intravenous (IV) dostarlimab or PBO Q3W (4 cycles), followed by 1000 mg IV dostarlimab or PBO Q6W (7 cycles). The primary endpoint is event-free survival (EFS); events are defined as locoregional progression/recurrence/metastasis per blinded independent central review assessment, salvage surgery, neck dissection/surgery >20 weeks after CRT completion, or death. Secondary endpoints include overall survival, EFS per investigator assessment, safety, tolerability, pharmacokinetics, and anti-drug antibodies incidence.

Clinical trial identification

NCT06256588.

Editorial acknowledgement

This study (GSK Study 221530; NCT06256588) was funded by GSK. Medical writing support was provided by Nicholas Thomas, PhD, at Fishawack Indicia Ltd, part of Avalere Health, and was funded by GSK.

Legal entity responsible for the study

GSK.

Funding

GSK.

Disclosure

J. Machiels: Financial Interests, Institutional, Advisory Board, Advisory board member or speaker with honoraria (managed by my Institution): Pfizer, Roche, Bayer, Merck Serono, Boerhinger, BMS, Novartis, Incyte, Cue Biopharma, ALX Oncology, iTEOS, eTheRNA, NEKTAR, F-Star, Seagen, Genmab, Astellas, CureVac, MSD, GSK, Merus; Financial Interests, Personal, Other, Travel expenses: Amgen, BMS, Pfizer, MSD, Gilead, Sanofi; Financial Interests, Personal, Other, Data safety monitoring board with honoraria: Psioxus; Non-Financial Interests, Personal, Other, Investigator and study coordinator, H & N group Chair: EORTC; Financial Interests, Institutional, Research Funding, Institutional conflict of interest (Funding to institution for research support): all companies: Pfizer, Roche, Bayer, Merck Serono, Boehringer Ingelheim, BMS, Novartis, Incyte, Cue Biopharma, ALX Oncology, iTEOS, eTheRNA, NEKTAR, F-Star, Seagen, Genmab, Astellas, CureVac, MSD, GSK, Merus, EORTC, Amgen, MSD, Gilead, Sanofi, Psioxus. B. Burtness: Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Coordinating PI: GSK; Financial Interests, Personal, Research Funding: GSK. K.J. Harrington: Financial Interests, Institutional, Steering Committee Member: GSK, AstraZeneca; Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Local PI: AstraZeneca; Financial Interests, Personal, Advisory Board: MSD, Merck-Serono; Financial Interests, Personal, Invited Speaker: MSD, Merck-Serono; Financial Interests, Personal, Local PI: MSD; Financial Interests, Personal, Steering Committee Member: MSD, Merck-Serono; Financial Interests, Personal, Research Funding: Merck-Serono; Financial Interests, Personal, Speaker, Consultant, Advisor: Merck-Serono. N.F. Saba: Financial Interests, Institutional, Full or part-time Employment: Winship Cancer Institute – Emory University; Financial Interests, Personal, Advisory Board: AstraZeneca Eisai Medical Merck Merck EMD Serono, Pfizer, Kura, Vaccinex, CUE, BionTech, GSK, TOSK, Seagen, Flamingo, Infinity, Inovio, Aveo, Medscape, Onclive, Uptodate, BMS, Cornerstone, Celldex, Surface Oncology Astex, Imugene, Faron Pharmaceutical, Exelixis, Vaccinex; Financial Interests, Personal, Advisory Role: AstraZeneca Eisai Medical Merck Merck EMD Serono, Pfizer, Kura, Vaccinex, CUE, BionTech, GSK, TOSK, Seagen, Flamingo, Infinity, Inovio, Aveo, Medscape, Onclive, Uptodate, BMS, Cornerstone, Celldex, Surface Oncology Astex, Imugene, Faron Pharmaceutical, Exelixis, Vaccinex; Financial Interests, Personal, Funding: Exelixis, Vaccinex. M. Tahara: Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, Boehringer Ingelheim, Lilly, Merck Biopharma, MSD, Ono pharma, Pfizer, Rakuten Medical; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Eisai, Novartis; Financial Interests, Institutional, Local PI: AstraZeneca, Bayer, Bristol Myers Squibb, GSK, Lilly, Loxo, Merck biophama, MSD, Novartis, Ono Pharma, Pfizer, Rakuten Medical; Financial Interests, Institutional, Research Grant: Bayer. T. Crossman, A.D. Perera, E. Zografos: Financial Interests, Personal, Full or part-time Employment: GSK; Financial Interests, Personal, Stocks or ownership: GSK. L. Hua: Financial Interests, Personal and Institutional, Full or part-time Employment: GSK; Financial Interests, Personal and Institutional, Stocks or ownership: GSK. D.S. Theti: Financial Interests, Personal, Full or part-time Employment: GSK; Financial Interests, Personal, Stocks or ownership: GSK, Pfizer. L.L. Siu: Financial Interests, Personal, Advisory Board: Merck, Pfizer, AstraZeneca, Roche, GSK, Voronoi, Arvinas, Navire, Relay, Marengo, Daiichi Sankyo, Amgen, Medicenna, LTZ Therapeutics, Tubulis, Marengo, Nerviano, Pangea, Incyte, Gilead; Financial Interests, Institutional, Research Funding: Merck, Novartis, Bristol Myers Squibb, Pfizer/SeaGen, Boerhinger Ingelheim, GSK, Roche/Genentech, AstraZeneca/Medimmune, Bayer, Abbvie, Amgen, Symphogen, EMD Serono, 23Me, Daiichi Sankyo, Gilead, Marengo, Incyte, LegoChem, Loxo/Eli Lilly, Med; Financial Interests, Personal, Stocks or ownership: Agios; Financial Interests, Personal, Leadership Role: Treadwell Therapeutics.