Abstract 703TiP
Background
This study will assess whether setanaxib, an investigational nicotinamide adenine dinucleotide phosphate oxidase (NOX) 1/4 inhibitor (Calliditas Therapeutics Suisse SA), could increase cancer-associated fibroblast (CAF)-rich tumour response to pembrolizumab in patients (pts) with recurrent/metastatic squamous cell carcinoma of the head and neck (rmSCCHN). Pembrolizumab, a programmed cell death-1 inhibitor, is indicated as first-line treatment (tx) for rmSCCHN in some pts; however, tumour response rates are low.1,2 CAF-rich tumours suppress response to immunotherapy by excluding cluster of differentiation (CD)8+ tumour-infiltrating lymphocytes (TILs).3NOX1/4 are key drivers of fibrogenesis. Pre-clinical models suggest that, as NOX4 inhibition by setanaxib may prevent and reverse differentiation of CAFs, combination tx of setanaxib with pembrolizumab may improve clinical outcomes in CAF-rich tumours.3
Trial design
In this double-blind, placebo-controlled phase 2 trial (NCT05323656), 60 pts with rmSCCHN (Table) will be randomised 1:1 (stratified by tumour human papillomavirus status) to oral setanaxib 800 mg twice daily or placebo, plus intravenous pembrolizumab 200 mg every 3 weeks, for ≤24 months. The primary objective will be to evaluate and compare best percentage change from baseline in tumour diameter (using Response Evaluation Criteria in Solid Tumours [RECIST] 1.1) between tx arms. Key secondary objectives will include comparisons of progression-free survival per RECIST 1.1 and change from baseline in tumour CAF and CD8+ TIL levels between tx arms. The study is currently recruiting in France, Germany, Poland, Spain, the UK and the USA. 1NICE https://www.nice.org.uk/guidance/ta661/ accessed 13/04/22; 2Bauml J Clin Oncol 2017;35:1542–9; 3Ford K Cancer Res 2020;80:1846–60. Table: 703TiP
Key eligibility criteria
| CAF: cancer-associated fibroblast; HPV: human papillomavirus; PD-L: programmed death-ligand; RECIST: Response Evaluation Criteria in Solid Tumours; rmSCCHN: recurrent/metastatic squamous cell carcinoma of the head and neck | |
| Inclusion | Exclusion |
| Aged ≥18 years Histologically/cytologically confirmed rmSCCHN HPV status known at randomisation Tumour CAFs level ≥5% First-line pembrolizumab candidate PD-L1 combined positive score ≥1 Measurable disease (RECIST 1.1) Tumour suitable for biopsy | Active central nervous system metastases Prior pembrolizumab/setanaxib Active autoimmune disease in past 3 months/immunosuppression diagnosis Systemic steroid therapy ≤7 days prior to first dose |
Clinical trial identification
NCT05323656.
Editorial acknowledgement
The authors acknowledge Krassimir Mitchev, MD, PhD, Calliditas Therapeutics AB, London, UK, for publication coordination and Tara Groves, BSc, Olivia Wakeman, BSc, and Sarah Jayne Clements, PhD, from Costello Medical, Cambridge, UK, for medical writing and editorial assistance based on the authors’ input and direction.
Legal entity responsible for the study
Calliditas Therapeutics Suisse SA.
Funding
Calliditas Therapeutics Suisse SA.
Disclosure
D.R. Adkins: Financial Interests, Advisory Role, Consulting: Merck, Cue Biopharma, Blue Print, Exelixis, Kura, Twoxar, Vaccinex, Xilio, Targimmune, Immunitas, Coherus, Eisai. P. Bossi: Financial Interests, Advisory Board, Advisory Board or Conference Honoraria: Merck, Sanofi-Regeneron, Merck Sharp & Dohme, Sun Pharma, Angelini, Molteni, Bristol Myers Squibb, GSK, Nestlé. E.E.W. Cohen: Financial Interests, Advisory Role, Consulting: Axelia, Cel Sci, Eisai, Hoopika, ImmunoSensor, Istari, Janssen, Kahr Medical, Mana Therapeutics, Merck, Mirati, MSD, Nectin Tx, Pangea Therapeutics, Roche; Financial Interests, Other, Data and Safety Monitoring Board: Ayala, Kura; Financial Interests, Member of the Board of Directors: National Comprehensive Cancer Network, Psioxus Therapeutics; Financial Interests, Stocks/Shares: Kinnate Biopharma, Primmune Therapeutics; Financial Interests, Advisory Board: Kinnate Biopharma. A. Daste: Financial Interests, Advisory Role, Consulting: Merck, Bristol Myers Squibb, MSD; Financial Interests, Advisory Board: Merck, Bristol Myers Squibb. K.J. Harrington: Financial Interests, Research Grant: AstraZeneca, Boehringer Ingelheim, MSD, Replimune; Financial Interests, Advisory Board: AstraZeneca, Arch Oncology, Bristol Myers Squibb, Boehringer Ingelheim, Codiak, Inzen, Merck Serono, MSD, Pfizer, Replimune. C. Le Tourneau: Financial Interests, Advisory Board: MSD, Bristol Myers Squibb, Merck Serono, Celgene, Roche, AstraZeneca, Nanobiotix, Seattle Genetics. L.F. Licitra: Financial Interests, Institutional, Research Grant: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Celgene International, Eisai, Exelixis, Debiopharm International SA, Hoffmann-La Roche ltd, IRX Therapeutics, Medpace, Merck Serono, MSD, Novartis, Pfizer, Roche, Buran; Financial Interests, Invited Speaker, Speaker Fees/Advisory Board: AstraZeneca, Bayer, MSD, Merck Serono, AccMed, Neutron Therapeutics, Inc. N. Little: Financial Interests, Personal, Advisory Role, Consulting: Calliditas Therapeutics AB. T. Morris: Financial Interests, Member of the Board of Directors: Oncotherics Ltd; Financial Interests, Advisory Role, Consulting: AstraZeneca Plc, Prism Ideas Ltd, Aptus Clinical Ltd, Medivir AB, Ascelia Pharma AB, Evgen Pharma Plc, Calliditas Therapeutics AB. M. Reinwald: Financial Interests, Advisory Board, Advisory Board/Honoraria: Roche, Bristol Myers Squibb, Boehringer-Ingelheim, AstraZeneca; Financial Interests, Research Grant: Gilead, Pfizer, Roche. All other authors have declared no conflicts of interest.