Abstract 538P
Background
Interleukin-1 Receptor Accessory Protein (IL1RAP) is expressed on cancer and stromal cells in many tumors. IL-1 pathway is upregulated in response to cytotoxics as a survival signal. CAN04 targets IL1RAP, blocking IL-1α and β signaling and triggering antibody-dependent cellular cytotoxicity. CAN04 has been assessed as monotherapy without reaching maximum tolerated dose (Awada el al. ASCO 2019). We report the results of CAN04 in combination with gemcitabine/nab-paclitaxel (PDAC) and gemcitabine/cisplatin (NSCLC).
Methods
Primary objective was to determine safety of CAN04 in combination with standard of care chemotherapy. Efficacy by iRECIST is a secondary endpoint. Initial CAN04 dose was 5 mg/kg weekly. Priming dose of 0.5 mg/kg was given on Day -7 to reduce the risk of infusion related reaction (IRR).
Results
58 pts were available for safety analysis: 36 with PDAC (enrollment completed) and 22 with NSCLC (enrollment ongoing). Median age 58 years (39-87), 45% female, 60% ECOG 0, 87% stage IV. PDAC patients were all first line; 9 (41%) of NSCLC patients had received previous pembrolizumab monotherapy. G1/2 IRRs were observed in 40% (G3 3%); 61% occurred at the priming dose. Most frequent (>10%) G3/4 adverse events (AE): neutropenia 64%, thrombocytopenia 24%, infection 24%, febrile neutropenia 19%, and anemia 17%. In 33 PDAC evaluable patients, Objective response rate (ORR) is 27%, clinical benefit rate 57.6%. Median duration of response (DoR) 6.5 mo (range 1.9 to 13.8). 5 pts with initial PD at first evaluation showed benefit beyond progression per iRECIST with concomitant CA19-9 reduction. iPFS per iRECIST is 7.8 mo [95% CI: 5.2-10.2] with 50% of events. Median OS is 12.6 mo [95% CI not estimable] and 1-year survival 55%. 15 NSCLC pts are so far included in the efficacy analysis. ORR is 60% (1 CR, 6 confirmed PR, 2 unconfirmed PR ongoing), median DoR is 6.2 mo (3.4 to 18.7). Median PFS is 8.2 mo [95% CI: 6.4-11.1] with 40% still on treatment. 6 pts continued CAN04 monotherapy as maintenance >3 mo (3.7 to 14.5+).
Conclusions
CAN04 combined with standard chemotherapy shows encouraging activity in PDAC and NSCLC. Benefit beyond PD has been observed in several patients with PDAC.
Clinical trial identification
NCT03267316.
Editorial acknowledgement
Legal entity responsible for the study
Cantargia AB.
Funding
Cantargia AB.
Disclosure
A.H. Awada: Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Roche; Non-Financial Interests, Personal, Member: BSMO; Non-Financial Interests, Personal, Member of the Board of Directors: Fondation contra le cancer; Non-Financial Interests, Personal, Member of the Board of Directors: Oncodistinct network for clinical research; Non-Financial Interests, Personal, Advisory Role: Cantargia AB; Other, Personal, Other, Travel: Pfizer; Other, Personal, Other, Travel: Roche; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: Genomic Health; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Invited Speaker: Leo Pharma; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Invited Speaker: Daiichi; Financial Interests, Personal, Invited Speaker: SEattle Genetics. M. Zematis: Financial Interests, Personal, Other, Honoraria/travel: Roche; Financial Interests, Personal, Other, Honoraria/travel: AstraZeneca; Financial Interests, Personal, Other, Honoraria/travel: MSD; Financial Interests, Personal, Other, Honoraria/travel: Merck; Financial Interests, Personal, Other, Honoraria/travel: Pfizer; Financial Interests, Personal, Other, Honoraria/travel: Lilly. S. Ochsenreither: Financial Interests, Personal, Advisory Board, Honoraria/travel: MSD; Financial Interests, Personal, Advisory Board, Honoraria/travel: BMS; Financial Interests, Personal, Advisory Board, Honoraria/travel: Merck; Financial Interests, Personal, Advisory Board: Jansen; Financial Interests, Personal, Advisory Board, Honoraria/travel: Ipsen; Financial Interests, Personal, Advisory Board, Honoraria/travel: Pfizer; Financial Interests, Personal, Advisory Board: Curevac; Financial Interests, Personal, Advisory Board: AstraZeneca. R.L. Eefsen: Financial Interests, Personal, Expert Testimony: Amgen. D. Arnold: Financial Interests, Personal, Training: ACE Oncology; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Training: Aptitude Health; Financial Interests, Personal, Training: Art Tempi Media; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: Boston Scientific; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Advisory Board: Clinical Care Options; Financial Interests, Personal, Advisory Board: CRA international; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: From Research to Practice; Financial Interests, Personal, Advisory Board: Hexal; Financial Interests, Personal, Invited Speaker: Imedex; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Advisory Board: IQIVIA; Financial Interests, Personal, Advisory Board: Ketchum; Financial Interests, Personal, Invited Speaker: MedAhead; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: PharmaCept; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Invited Speaker: PRIMA consulting; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Samsung Bioepis; Financial Interests, Personal, Advisory Board: Samsung Bioepis; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Invited Speaker: Servier; Financial Interests, Personal, Invited Speaker: Streamitup; Financial Interests, Personal, Invited Speaker: Tactis; Financial Interests, Personal, Invited Speaker: Terumo; Financial Interests, Personal, Advisory Board: Terumo; Financial Interests, Personal, Invited Speaker: WebMD; Other, Personal, Other, Associated editor Clin Colorect Cancer: Elsevier; Other, Personal, Other, Associated editor Ann Oncol: Elsevier; Other, Personal, Other, Associated editor: Oxford University Press; Financial Interests, Institutional, Funding, Educational grant: AbbVie; Non-Financial Interests, Institutional, Principal Investigator: BMS; Non-Financial Interests, Institutional, Principal Investigator: OncoLytics; Non-Financial Interests, Institutional, Principal Investigator: Pierre Fabre; Non-Financial Interests, Institutional, Other, Steering Committee: Roche; Financial Interests, Institutional, Other, DSMB member: Sanofi; Financial Interests, Personal, Project Lead: Oncolytics; Non-Financial Interests, Personal, Member: AIO; Non-Financial Interests, Personal, Member: ASCO; Non-Financial Interests, Personal, Member: DGHO; Non-Financial Interests, Personal, Leadership Role: EORTC; Non-Financial Interests, Personal, Member: ESO. L. Paz-Ares: Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: AZ; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Advisory Board: Mirati; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: PharmaMar; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: Tesaro; Financial Interests, Personal, Member of the Board of Directors: Altum sequencing; Financial Interests, Institutional, Principal Investigator: Alkermes; Financial Interests, Personal, Principal Investigator: Amgen; Financial Interests, Institutional, Principal Investigator: AZ; Financial Interests, Institutional, Principal Investigator: BMS; Financial Interests, Institutional, Principal Investigator: Daiichi Sankyo; Financial Interests, Institutional, Principal Investigator: IO Biotech; Financial Interests, Institutional, Principal Investigator: Janssen clilag; Financial Interests, Institutional, Principal Investigator: Lilly; Financial Interests, Institutional, Principal Investigator: MSD; Financial Interests, Institutional, Principal Investigator: Novartis; Financial Interests, Institutional, Principal Investigator: Pfizer; Financial Interests, Institutional, Principal Investigator: PharmaMar; Financial Interests, Institutional, Principal Investigator: Roche; Financial Interests, Institutional, Principal Investigator: Sanofi; Financial Interests, Institutional, Principal Investigator: Takeda; Financial Interests, Institutional, Principal Investigator: Tesaro. R. Greil: Financial Interests, Personal, Advisory Role: Celgene; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Takeda; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Sandoz; Financial Interests, Personal, Advisory Role: Abbvie; Financial Interests, Personal, Advisory Role: Gilead; Financial Interests, Personal, Advisory Role: Daiichi Sankyo. E. Van Cutsem: Financial Interests, Institutional, Funding: Amgen; Financial Interests, Institutional, Funding: Merck Serono; Financial Interests, Institutional, Funding: Pfizer; Financial Interests, Institutional, Funding: Roche; Financial Interests, Institutional, Funding: Sanofi. I. Garcia Ribas: Financial Interests, Personal, Full or part-time Employment: Cantargia AB; Financial Interests, Personal, Stocks/Shares: Sanofi. L. Thorsson: Financial Interests, Personal, Full or part-time Employment: Cantargia AB. J.J. Collignon: Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Invited Speaker: Servier; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: Sirtex; Financial Interests, Personal, Invited Speaker: Celgene; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Invited Speaker: Novartis; Other, Personal, Other, Travel/Accomodation: Roche; Other, Personal, Other, Travel/Accomodation: Amgen; Other, Personal, Other, Travel/Accomodation: Novartis. All other authors have declared no conflicts of interest.