Abstract 1025TiP
Background
The immune checkpoint inhibitors against programmed death 1 (PD1) or its ligand (PD-L1) has demonstrated significant efficacy in multiple cancer types. Thus, selecting patients most likely to respond to these therapies is necessary. PD-L1 expression by immunohistochemistry has been proposed as a potential predictive biomarker of response. A statistically significant difference in Overall Response Rate (ORR) between PD-L1 positive and PD-L1 negative tumors has been reported. However, there is not a common reference standard for PD-L1 quantification. Moreover, some studies showed efficacy of anti PD1/PD-L1 independently of PD-L1 expression. Recently, association between PD1 mRNA levels and response to anti-PD1 monotherapy across several cancer types has been validated both in silico datasets and in clinical samples, being the 80th percentile of PD1 expressing tumors (PD1-high) strongly correlated with ORR (Pare. Ann Oncol. 2019). We hypothesize that anti-PD1 monotherapy is effective across multiple cancer-types in patients with high mRNA PD1-expressing tumors.
Trial design
ACROPOLI is an open-label, single-arm, non-randomized, phase II study to evaluate the efficacy of the anti-PD-1 spartalizumab in monotherapy in patients with advanced solid PD1-high-expressing tumors (31 different cancer types). Patients could have received any number of previous lines other than immune checkpoint inhibitors. Patients with high levels of PD1 mRNA (Cohort 1; N= 111), as defined by the pre-specified cutoff, will be enrolled in the study. A cohort of 30 patients with PD1-low tumors where the efficacy of PD1 inhibitors in monotherapy has been previously established will also be recruited (Cohort 2). Patients will receive spartalizumab 400 mg/4 weeks. Primary objective is to determine ORR in the PD1-high population. Secondary objectives include other measures of clinical efficacy both in Cohort-1 and 2 (ORR, Clinical Benefit Rate, Progression-Free Survival, Duration of Response, Overall Survival) and evaluation of safety and tolerability. No formal comparison will be performed between two cohorts. Recruitment (10 sites in Spain) started in May 2021.
Clinical trial identification
NCT04802876.
Editorial acknowledgement
Legal entity responsible for the study
SOLTI.
Funding
Novartis.
Disclosure
A. Prat: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: Nanostring Technologies; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Puma; Financial Interests, Personal, Advisory Role: Oncolytics Biotech; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Guardant Health; Financial Interests, Personal, Advisory Role: Peptomyc; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Leadership Role: Reveal Genomics, SL; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Nanostring; Financial Interests, Institutional, Research Grant: Sysmex Europa GmbH; Financial Interests, Institutional, Research Grant: Medica Scientia inno. Research, SL; Financial Interests, Institutional, Research Grant: Celgene; Financial Interests, Institutional, Research Grant: Astellas; Financial Interests, Institutional, Research Grant: Pzifer; Financial Interests, Institutional, Other, Lecture Fees: Nanostring technologies; Financial Interests, Institutional, Other, Clinical Trials: Boehringer Ingelheim; Financial Interests, Institutional, Other, Clinical Trials: Lilly; Financial Interests, Institutional, Other, Clinical Trials: Roche; Financial Interests, Institutional, Other, Clinical Trials: Novartis; Financial Interests, Institutional, Other, Clinical Trials: Amgen; Financial Interests, Institutional, Other, Clinical Trials: Daiichi Sankyo; Financial Interests, Personal, Leadership Role: Beast International Group (BIG); Financial Interests, Personal, Leadership Role: SOLTI Cooperative Group; Financial Interests, Personal, Other, Patronage Committee: SOLTI Foundation; Financial Interests, Personal, Other, Patronage Committee: Actitud Frente al Cáncer Foundation. E. Felip: Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Beigene; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: F. Hoffman-La Roche; Financial Interests, Personal, Advisory Board: Glaxo Smith Kline; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Medical Trends; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Advisory Board: Peptomyc; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Puma; Financial Interests, Personal, Advisory Board: Regeneron; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Syneos Health; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Speaker’s Bureau: Amgen; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Bristol-Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: Eli Lilly; Financial Interests, Personal, Speaker’s Bureau: F. Hoffmann-La Roche; Financial Interests, Personal, Speaker’s Bureau: Janssen; Financial Interests, Personal, Speaker’s Bureau: Medscape; Financial Interests, Personal, Speaker’s Bureau: Merck Sharp & Dohme; Financial Interests, Personal, Speaker’s Bureau: Merck Serono; Financial Interests, Personal, Speaker’s Bureau: Peervoice; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Springer; Financial Interests, Personal, Speaker’s Bureau: Touch Medical; Financial Interests, Personal, Other, Independent Member Of The Board: Grifols; Financial Interests, Personal, Other, Research Funding to Institution: Fundación Merck Salud. A.M. Arance Fernandez: Financial Interests, Personal, Other, Consultant: Pierre Fabre; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Pierre Fabre; Financial Interests, Institutional, Funding: Pierre Fabre; Financial Interests, Personal, Other, Consultant: Novartis; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Other, Travel Accommodations, Expenses: Novartis; Financial Interests, Institutional, Funding: Novartis; Financial Interests, Personal, Invited Speaker, Consultant: Roche; Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Other, Travel Accommodations, Expenses: Roche; Financial Interests, Institutional, Funding: Roche; Financial Interests, Personal, Other, Consultant: BMS; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Other, Travel Accommodations, Expenses: BMS; Financial Interests, Institutional, Funding: BMS; Financial Interests, Personal, Other, Consultant: MSD; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Other, Travel Accommodations, Expenses: MSD; Financial Interests, Institutional, Funding: MSD; Financial Interests, Personal, Other, Consultant: Merck; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Other, Travel Accommodations, Expenses: Merck; Financial Interests, Institutional, Funding: Merck; Financial Interests, Personal, Other, Consultant: Sanofi; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Other, Travel Accommodations, Expenses: Sanofi; Financial Interests, Institutional, Funding: Sanofi; Financial Interests, Institutional, Funding: Amgem. J. Martin-Liberal: Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Research Grant: Sanofi; Financial Interests, Personal, Other, Travel Accommodations, Expenses: Bristol-Myers Squibb; Financial Interests, Personal, Other, Travel: MSD; Financial Interests, Personal, Other, Travel: Novartis; Financial Interests, Personal, Other, Travel: Pierre Fabre; Financial Interests, Personal, Other, Travel: Pfizer; Financial Interests, Personal, Other, Travel: Roche; Financial Interests, Personal, Other, Travel: Ipsen. J. Gavilá: Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Personal, Other: Novartis; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Personal, Other: Pfizer; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Personal, Other: Roche. C. Saura Manich: Financial Interests, Personal, Other, Consultant: AstraZeneca; Financial Interests, Personal, Other, Consultant: Daiichi Sankyo; Financial Interests, Personal, Other, Consultant: Eisai; Financial Interests, Personal, Other, Consultant: Exact Sciences; Financial Interests, Personal, Other, Consultant: Exeter Pharma; Financial Interests, Personal, Other, Consultant: F. Hoffmann - La Roche Ltd; Financial Interests, Personal, Other, Consultant: MediTech; Financial Interests, Personal, Other, Consultant: Merck Sharp & Dohme; Financial Interests, Personal, Other, Consultant: Novartis; Financial Interests, Personal, Other, Consultant: Pfizer; Financial Interests, Personal, Other, Consultant: Philips; Financial Interests, Personal, Other, Consultant: Pierre Fabre; Financial Interests, Personal, Other, Consultant: Puma; Financial Interests, Personal, Other, Consultant: Sanofi; Financial Interests, Personal, Other, Consultant: Aventis; Financial Interests, Personal, Other, Consultant: SeaGen; Financial Interests, Personal, Other, Consultant: Zymeworks; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Exact Sciences; Financial Interests, Personal, Advisory Board: Exeter Pharma; Financial Interests, Personal, Advisory Board: F. Hoffmann - La Roche Ltd; Financial Interests, Personal, Advisory Board: MediTech; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Philips; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: Puma; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Aventis; Financial Interests, Personal, Advisory Board: SeaGen; Financial Interests, Personal, Advisory Board: Zymeworks; Financial Interests, Personal, Other, Travel Grants: AstraZeneca; Financial Interests, Personal, Other, Travel Grants: Daiichi Sankyo; Financial Interests, Personal, Other, Travel Grants: Eisai; Financial Interests, Personal, Other, Travel Grants: Exact Sciences; Financial Interests, Personal, Other, Travel Grants: Exeter Pharma; Financial Interests, Personal, Other, Travel Grants: F. Hoffmann - La Roche Ltd; Financial Interests, Personal, Other, Travel Grants: MediTech; Financial Interests, Personal, Other, Travel Grants: Merck Sharp & Dohme; Financial Interests, Personal, Other, Travel Grants: Novartis; Financial Interests, Personal, Other, Travel Grants: Pfizer; Financial Interests, Personal, Other, Travel Grants: Philips; Financial Interests, Personal, Other, Travel Grants: Pierre Fabre; Financial Interests, Personal, Other, Travel Grants: Puma; Financial Interests, Personal, Other, Travel Grants: Sanofi; Financial Interests, Personal, Other, Travel Grants: Aventis; Financial Interests, Personal, Other, Travel Grants: SeaGen; Financial Interests, Personal, Other, Travel Grants: Zymeworks; Financial Interests, Institutional, Other: AstraZeneca; Financial Interests, Institutional, Other: Daiichi Sankyo; Financial Interests, Institutional, Other: Eli Lilly and Company; Financial Interests, Institutional, Other: Genentech; Financial Interests, Institutional, Other: Immunomedics; Financial Interests, Institutional, Other: Macrogenics; Financial Interests, Institutional, Other: Merck Sharp and Dhome España S.A; Financial Interests, Institutional, Other: Novartis; Financial Interests, Institutional, Other: Pfizer; Financial Interests, Institutional, Other: Piqur Therapeutics; Financial Interests, Institutional, Other: Puma; Financial Interests, Institutional, Other: Roche; Financial Interests, Institutional, Other: Synthon; Financial Interests, Institutional, Other: Zenith Pharma. J. Tabernero: Financial Interests, Personal, Other, Consultant: Array Biopharma; Financial Interests, Personal, Invited Speaker, Consultant: AstraZeneca; Financial Interests, Personal, Invited Speaker, Consultant: Avvinity; Financial Interests, Personal, Invited Speaker, Consultant: Bayer; Financial Interests, Personal, Invited Speaker, Consultant: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker, Consultant: Chugai; Financial Interests, Personal, Invited Speaker, Consultant: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker, Consultant: F. Hoffmann La Roche Ltd; Financial Interests, Personal, Invited Speaker, Consultant: Genentech Inc; Financial Interests, Personal, Invited Speaker, Consultant: HalioDX SAS; Financial Interests, Personal, Invited Speaker, Consultant: Hutchison MediPharma International; Financial Interests, Personal, Invited Speaker, Consultant: Ikena Oncology; Financial Interests, Personal, Invited Speaker, Consultant: IQVIA; Financial Interests, Personal, Invited Speaker, Consultant: Lilly; Financial Interests, Personal, Invited Speaker, Consultant: Menarini; Financial Interests, Personal, Invited Speaker, Consultant: Merck Serono; Financial Interests, Personal, Invited Speaker, Consultant: Merus; Financial Interests, Personal, Invited Speaker, Consultant: MSD; Financial Interests, Personal, Invited Speaker, Consultant: Mirati; Financial Interests, Personal, Invited Speaker, Consultant: Neophore; Financial Interests, Personal, Invited Speaker, Consultant: Novartis; Financial Interests, Personal, Invited Speaker, Consultant: Orion Biotechnology; Financial Interests, Personal, Invited Speaker, Consultant: Peptomyc; Financial Interests, Personal, Invited Speaker, Consultant: Pfizer; Financial Interests, Personal, Invited Speaker, Consultant: Pierre Fabre; Financial Interests, Personal, Invited Speaker, Consultant: Samsung Bioepis; Financial Interests, Personal, Invited Speaker, Consultant: Sanofi; Financial Interests, Personal, Invited Speaker, Consultant: Seattle Genetics; Financial Interests, Personal, Invited Speaker, Consultant: Servier; Financial Interests, Personal, Invited Speaker, Consultant: Taiho; Financial Interests, Personal, Invited Speaker, Consultant: Tessa Therapeutics; Financial Interests, Personal, Invited Speaker, Consultant: TheraMyc; Financial Interests, Personal, Expert Testimony: Imedex; Financial Interests, Personal, Expert Testimony: Medscape Education; Financial Interests, Personal, Expert Testimony: MJH Life Sciences; Financial Interests, Personal, Expert Testimony: PeerView Institute for Medical Education; Financial Interests, Personal, Expert Testimony: Physicians Education Resource (PER). All other authors have declared no conflicts of interest.