Phase I/II trial shows promising efficacy of nadunolimab in combination with platinum doublet as second-line therapy in patients with NSCLC

BackgroundInterleukin-1 Receptor Accessory Protein (IL1RAP), expressed in several tumors, is essential for IL-1α and IL-1β signaling. IL-1α/IL-1β are implicated in tumor progression and therapy resistance, and platinum chemotherapy upregulates IL-1α in non-small cell lung cancer (NSCLC). Nadunolimab, a fully humanized ADCC-enhanced IgG1 antibody, targets IL1RAP and blocks IL-1α/IL-1β signaling. Here, data are reported from the phase I/IIa clinical trial CANFOUR in NSCLC pts treated with nadunolimab and platinum doublet.MethodsPts with advanced NSCLC, 1st or 2nd line (1L/2L), received nadunolimab at 1 (n=16), 2.5 (n=3) or 5 mg/kg (n=11) with cisplatin/gemcitabine, or at 2.5 mg/kg with carboplatin/pemetrexed (n=10). As an exploratory objective, the composition of immune cells in baseline biopsies were analyzed by immunohistochemistry and baseline serum samples by Olink.ResultsEfficacy parameters for nadunolimab and platinum doublet treatment (n=40) are summarized in the table below. The total population showed a promising OS and PFS of 13.7 and 6.8 months. Stronger efficacy was seen in 2L pts (n=18 in total; n=17 post-pembrolizumab) compared to 1L pts (n=22) (ORR 72% vs 41%; PFS 7.6 mo vs 6.7 mo, p = 0.038; OS 15.7 mo vs 11.5 mo). Biopsy analyses showed that 2L pts had a higher number of IL1RAP-positive immune cells, CD163+ macrophages, CD56+ NK cells and CD8+ T cells in the tumor at baseline. Serum markers showed a T-cell inflammatory profile with increased IFNγ, CXCL9 and CXCL10. Efficacy results were most pronounced in 2L non-squamous pts (n=12; ORR 92%, OS 28.9 mo; PFS 13.0 mo) including two complete responders. Table: 1350P All Non-squamous Efficacy parameter Total (n=40) 1L (n=22) 2L (n=18) 1L (n=14) 2L (n=12) OS; median, mo 13.7 11.5 15.7 11.9 28.9 PFS; median, mo 6.8 6.7 7.6 5.5 13.0 1-year survival 55% (36-70) 39% (16-61) 70% (42-86) 38% (10-67) 82% (45-95) ORR 55% 41% 72% 29% 92% DoR; median, mo 5.8 5.2 9.1 4.8 11.2 ConclusionsNadunolimab plus platinum doublet shows promising efficacy in NSCLC pts. Pts who progressed on pembrolizumab retained an inflammatory profile, although with signs of immunosuppression, and responded strongly to nadunolimab and platinum doublet combination.Clinical trial identificationNCT05116891.Legal entity responsible for the studyCantargia AB.FundingCantargia AB.DisclosureA. Paulus: Other, Funding: Amgen. M. Zemaitis: Financial Interests, Personal, Advisory Role: AstraZeneca, MSD, Janssen, Swixx Biopharma; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, MSD, Swixx Biopharma, Roche, Lilly. C. Rydberg-Millrud, S. Magnusson, N. Losic: Financial Interests, Personal, Full or part-time Employment: Cantargia; Financial Interests, Personal, Stocks/Shares: Cantargia. D. Tersago: Financial Interests, Personal, Speaker, Consultant, Advisor, Consultant: Cantargia. L.G. Paz-Ares: Financial Interests, Personal, Advisory Board, Speaker fees: Roche, MSD, BMS, AZ, Lilly, PharmaMar, BeiGene, Daiichi Sankyo, Medscape, PER; Financial Interests, Personal, Advisory Board: Merck Serono, Pfizer, Bayer, Amgen, Janssen, GSK, Novartis, Takeda, Sanofi, Mirati, Boehringer; Financial Interests, Personal, Other, Board member: Genomica, Altum sequencing; Financial Interests, Personal, Other, lectures: AICME; Financial Interests, Personal, Other, Lectures: CCO; Financial Interests, Personal, Member of Board of Directors, Board member: Stab Therapeutics; Financial Interests, Personal, Other, spinn off (I have arounfd 8% of stocks): Altum sequencing; Financial Interests, Personal, Ownership Interest, spin-off (10%): Stab Therapeutics; Financial Interests, Institutional, Coordinating PI: Daiichi Sankyo, AstraZeneca, Merck Sharp & Dohme Corp, BMS, Janssen-Cilag international NV, Novartis, Roche, Sanofi, Tesaro, Alkermes, Lilly, Takeda, Pfizer, PharmaMar; Financial Interests, Personal, Coordinating PI: Amgen; Financial Interests, Other, Member: AACR, ASCO, ESMO; Financial Interests, Other, Foundation Board Member: AECC; Financial Interests, Other, President ASEICA (Spanish Association of CancerResearch): ASEICA; Financial Interests, Other, Foundation president: ONCOSUR; Financial Interests, Other, member: Small Lung Cancer Group; Non-Financial Interests, Other, Board member of this anti-cancer Charity: AECC; Non-Financial Interests, Member, Past-President: ASEICA (Spanish Cancer Research Association); Non-Financial Interests, Leadership Role, President: Oncosur Foundation. All other authors have declared no conflicts of interest.