120MO - Inupadenant combined with chemotherapy in patients with non-squamous NSCLC progressing on or after immune checkpoint inhibitor therapy: Results from dose-finding part of the A2A-005 trial

Background

Immunosuppressive adenosine accumulates at high levels in advanced non-small cell lung cancer (NSCLC), where treatment options remain limited following immune checkpoint inhibitor (ICI) therapy. Inupadenant, a selective adenosine-2A receptor (A2AR) inhibitor, counteracts the adenosine immunosuppressive effects. Combining inupadenant with standard chemotherapy may enhance anti-tumor immunity leading to more durable clinical outcomes in advanced NSCLC.

Methods

In the dose finding part of this phase 1/2, open-label trial, participants with advanced, non-squamous NSCLC who progressed after ICI therapy underwent dose escalation of inupadenant combined with standard carboplatin and pemetrexed chemotherapy (NCT05403385). The primary endpoint for this part was safety and tolerability of the combination. Secondary endpoints included PK and efficacy.

Results

At data cutoff (30 Aug 2024), 36 participants were treated across 3 dose levels of inupadenant, (40, 60 and 80 mg), combined with chemotherapy. All participants experienced treatment-emergent adverse events (TEAEs); most common events reported across all doses included anemia (67%), constipation (44%), diarrhea (39%), asthenia (39%), fatigue (39%) and neutropenia (36%). High grade events (Grade ≥3) reported in 69% participants were mostly laboratory abnormalities consistent with known chemotherapy toxicities. MTD was not reached. RECIST 1.1 responses were observed in 23 (64%) participants. The highest ORR of 73%, including 2 confirmed CR’s, was observed at the 80 mg dose. A total of 34 participants had at least 6 months follow up; median PFS in this subset was 7.7 months (95% CI 4.9,11.0). Preliminary translational analyses indicate that serum CXCL13 increase may be associated with responses.

Conclusions

The combination of inupadenant and carboplatin-pemetrexed had a manageable safety profile and preliminary clinical activity in advanced NSCLC post ICI therapy. The study is ongoing and updated safety, efficacy, and translational data will be presented.

Clinical trial identification

EudraCT 2021-005487-22, Release date: 6th October 2021. EU CTR number 2024-515393-27-00.

Legal entity responsible for the study

iTeos Therapeutics.

Funding

iTeos Therapeutics.

Disclosure

K. Cuppens: Financial Interests, Personal, Advisory Board: F. Hoffmann-La Roche, AstraZeneca, Pfizer, Merck Sharp & Dohme, AstraZeneca, Bristol Myers Squibb, Pierre Fabre Oncology, Amgen, Daiichi Sankyo, Janssen, Iteos Therapeutics; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Merck Sharp & Dohme, Hoffmann-La Roche, Janssen, Merck Sharp & Dohme. G. Lo Russo: Financial Interests, Personal, Advisory Board: MSD, Novartis, AstraZeneca, BMS, Sanofi, Pfizer, Roche, Lilly, GSK, Daichi, Johnson and Johnson, Regeneron, Merck, Pierre Fabre; Financial Interests, Personal, Invited Speaker: Italfarmaco; Financial Interests, Institutional, Other, Contribute For Meeting Organization: Janssen; Financial Interests, Institutional, Other, Contribute For Meeting Organization: Bayer; Financial Interests, Personal, Other, Travel Accommodation: Amgen, MSD; Financial Interests, Institutional, Other, Contribute To Meeting Organization: Beigene; Financial Interests, Personal, Writing Engagement: Merck, BMS, Lilly; Financial Interests, Institutional, Local PI: MSD, BMS, Roche, GSK, Celgene, Novartis, AstraZeneca, Amgen, Lilly; Financial Interests, Personal, Local PI: Sanofi. O.J. Juan Vidal: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Roche/Genentech, Lilly, Takeda, AstraZeneca, Janssen; Financial Interests, Personal, Other, Travel expenses: MSD; Financial Interests, Personal, Invited Speaker: Bristol Myers Squib, Amgen, Roche/Genentech, Pfizer; Financial Interests, Institutional, Funding: AstraZeneca. E. Felip: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AstraZeneca, Bayer, Beigene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Gilead, GSK, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, Peptomyc, Regeneron, Sanofi, Takeda, Turning Point, Pfizer, Genmab; Financial Interests, Personal, Invited Speaker: Amgen, Daiichi Sankyo, Genentech, Janssen, Medical Trends, Medscape, Merck Serono, Peervoice, Pfizer, Sanofi, Takeda, AstraZeneca, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Merck Sharp & Dohme; Financial Interests, Personal, Member of Board of Directors, Independent member: Grifols; Financial Interests, Institutional, Local PI, Clinical Trial: AstraZeneca AB, AbbVie, Amgen, Bayer Consumer Care AG, Beigene, Boehringer Ingelheim GmbH, Bristol Myers Squibb International Corporation, Daiichi Sankyo Inc., Exelixis Inc., F. Hoffmann-La Roche Ltd., Genentech Inc., Glaxo Smith Kline Research and Development Limited, Janssen Cilag International NV, Merck Sharp & Dohme Corp, Merck KGAA, Mirati Therapeutics Inc., Novartis Pharmaceutica SA, Pfizer, Takeda Pharmaceuticals International; Financial Interests, Institutional, Local PI: Nuvalent; Non-Financial Interests, Personal, Leadership Role, President (2021-2023): SEOM (Sociedad Espanola de Oncologia Medica); Non-Financial Interests, Personal, Member, Member of Scientific Committee: ETOP (European Thoracic Oncology Platform); Non-Financial Interests, Personal, Member, Member of the Scientific Advisory Committee: CAC Hospital Universitari Parc Taulí. M.C. Areses Manrique: Non-Financial Interests, Institutional, Principal Investigator: Complexo Hospitalario Universitario de Ourense. A. Chiappori: Financial Interests, Personal, Stocks/Shares: Merck. E. Govaerts: Non-Financial Interests, Personal, Principal Investigator: iTeos Therapeutics. P.K. Cheema: Financial Interests, Personal, Advisory Board: AstraZeneca, Amgen, Bristol Myers Squibb, Merck, Novartis, Hoffmann-La Roche, Janssen, GSK, Pfizer, Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Janssen, Merck, Daiichi Sankyo, Hoffman La Roche, Pfizer; Financial Interests, Personal, Steering Committee Member: AstraZeneca, Merck; Financial Interests, Institutional, Local PI: AstraZeneca, Bristol Myers Squibb, Taiho, Takeda, Hoffmann La Roche, iTEOS Therapeutics, Merck, Gilead, GSK. L. Greillier: Financial Interests, Personal, Advisory Board: AbbVie, AstraZeneca, BMS, MSD, Novartis, Sanofi, Takeda, Roche; Financial Interests, Personal, Invited Speaker: Lilly, Pfizer; Financial Interests, Institutional, Local PI: AstraZeneca, AbbVie, BMS, MSD, Novartis, Takeda, Pfizer, Roche, PharmaMar; Financial Interests, Institutional, Coordinating PI: Sanofi. L. Toschi: Non-Financial Interests, Institutional, Advisory Board: MSD, Sanofi, Roche, Novartis; Non-Financial Interests, Institutional, Invited Speaker, AstraZeneca: Lilly; Non-Financial Interests, Institutional, Invited Speaker: AstraZeneca. E. Schaefer: Non-Financial Interests, Institutional, Principal Investigator: iTeos Therapeutics. M. Clouseau, C. Martinoli, H. Shehade, N. Byrne: Financial Interests, Personal, Full or part-time Employment: iTeos Therapeutics; Financial Interests, Institutional, Stocks/Shares: AstraZeneca. O. De Henau: Financial Interests, Personal, Full or part-time Employment: iTeos Belgium SA; Financial Interests, Personal, Stocks/Shares: iTeos Belgium SA, Bristol Myers Squibb. S. Ross: Financial Interests, Personal, Full or part-time Employment, I am the Program Head for inupadenant and a Vice President within the company: iTeos Belgium; Financial Interests, Personal, Stocks/Shares, I own shares and share options granted as an employee of iTeos: iTeos Belgium. S. Peters: Financial Interests, Institutional, Advisory Board: Vaccibody, Takeda, Seattle Genetics, Sanofi, Roche/Genentech, Regeneron, Phosplatin Therapeutics, PharmaMar, Pfizer, Novartis, Mirati, Merck Serono, MSD, Janssen, Incyte, Illumina, IQVIA, GSK, Gilead, Genzyme, Foundation Medicine, F-Star, Eli Lilly, Debiopharm, Daiichi Sankyo, Boehringer Ingelheim, Blueprint Medicines, Biocartis, Bio Invent, BeiGene, Bayer, BMS, AstraZeneca, Arcus, Amgen, AbbVie, iTheos, Novocure; Financial Interests, Institutional, Invited Speaker: Takeda, Sanofi, Roche/Genentech, RTP, Pfizer, PRIME, PER, Novartis, Medscape, MSD, Imedex, Illumina, Fishawack, Eli Lilly, Ecancer, Boehringer Ingelheim, BMS, AstraZeneca, Oncology Education, RMEI, Mirati; Financial Interests, Personal, Other, Associate Editor Annals of Oncology and Deputy Editor Lung Cancer: Elsevier; Financial Interests, Institutional, Advisory Board, Permanent independent scientific advisor: Hutchmed; Financial Interests, Institutional, Member of Board of Directors, Swiss network of pharmacies: Galenica; Financial Interests, Institutional, Coordinating PI, MERMAID-1: AstraZeneca; Financial Interests, Institutional, Steering Committee Member, MERMAID-2, POSEIDON, MYSTIC: AstraZeneca; Financial Interests, Institutional, Steering Committee Member, Clinical Trial Steering committee CheckMate 743, CheckMate 73L, CheckMate 331 and 451: BMS; Financial Interests, Institutional, Steering Committee Member, RELATIVITY 095: BMS; Financial Interests, Institutional, Steering Committee Member, BGB-A317-A1217-301/AdvanTIG-301: Beigene; Financial Interests, Institutional, Trial Chair, Clinical Trial Chair ZEAL-1: GSK; Financial Interests, Institutional, Steering Committee Member, Clinical Trial steering Committee PEARLS, MK-7684A: MSD; Financial Interests, Institutional, Steering Committee Member, Clinical Trial Steering Committee SAPPHIRE: Mirati; Financial Interests, Institutional, Steering Committee Member, LAGOON: PharmaMar; Financial Interests, Institutional, Steering Committee Member, phase 1/2 trials: Phosplatin Therapeutics; Financial Interests, Institutional, Trial Chair, Clinical Trial Chair Skyscraper-01; chair ALEX; steering committee BFAST; steering committee BEAT-Meso; steering committee ImPower-030, IMforte: Roche/Genentech; Financial Interests, Institutional, Steering Committee Member, Phase 2 Inupadenant with chemo: iTeos; Non-Financial Interests, Personal, Officer, ESMO President 2020-2022: ESMO; Non-Financial Interests, Personal, Officer, Council Member & Scientific Committee Chair: ETOP/IBCSG Partners; Non-Financial Interests, Personal, Officer, Vice-President Lung Group: SAKK; Non-Financial Interests, Personal, Other, Involved in Swiss politics: Swiss Political Activities; Non-Financial Interests, Personal, Officer, President and Council Member: Ballet Béjart Lausanne Foundation; Non-Financial Interests, Personal, Principal Investigator, Involved in academic trials: ETOP / EORTC / SAKK; Non-Financial Interests, Personal, Member: Association of Swiss Physicians FMH (CH), ASCO, AACR, IASLC; Non-Financial Interests, Personal, Leadership Role, ESMO President: ESMO; Non-Financial Interests, Personal, Member, Vice-President Lung Group: SAKK; Non-Financial Interests, Personal, Leadership Role, Vice -President: SAMO; Non-Financial Interests, Personal, Member, Association of Swiss interns and residents: ASMAC/VSAO.