Abstract 928P
Background
ISU104 demonstrated anti-tumor efficacy in cetuximab-sensitive and -resistant preclinical models as monotherapy or combination therapy with CET. Dose-escalation study to evaluate the safety, tolerability and pharmacokinetics (PK) of ISU104 was conducted in various advanced solid tumor pts (Ann Oncol, abst #454 PD, 2019). Here we report a dose-expansion study (PART II).
Methods
R/M HNSCC pts, excluding nasopharyngeal cancer, were enrolled and allocated to ISU104 alone (20 mg/kg/day, Q3W; Mono, N=6) or in combination with CET (400 mg/m2 followed by 250 mg/m2, Q1W; Comb, N=12). The study evaluated safety, PK, anti-tumor efficacy and occurrence of anti-drug antibodies. Paired pre-and post-treatment biopsies were conducted to analyze biomarkers including EGFR, ERBB2, ERBB3, pERBB3, NRG1, HPV and other genetic alterations.
Results
Median age of the 18 pts was 62 (range; 30-76, M/F 15/3). As of 17th Jul. 2020, response assessments were available in 17 of 18 pts (4 ongoing, 2 withdrawn, 6 in Mono and 12 in Comb). Most common treatment emergent adverse events (TEAEs) included anorexia (66.7%), mucositis oral (50%) and diarrhea (33.3%) in Mono and diarrhea (75%) and acneiform rash (50%) in Comb. Serious AEs were reported 16.7% in Mono and 58.3% in Comb, but no AEs led to treatment discontinuation. Six pts had dose modification of ISU104 or/and CET in Comb and no case in Mono. Overall response rate and disease control rate were 0% and 50% (3 SD) in Mono (6 pts) and 36.4% (1 CR and 3 PR) and 81.8% (1 CR, 3 PR and 5 SD) in Comb (11 pts), respectively. Duration of response were 62, 46, 162+ and 170+ days (4 pts in Comb), and median progression-free survival was 45 days in Mono and 99 days in Comb group, respectively, with median follow-up of 156 days. Results from mature clinical efficacy data, biomarker analysis and PK will be presented.
Conclusions
ISU104 alone or combination with CET was safe and tolerable with encouraging clinical outcomes in R/M HNSCC treated with Comb. A phase II study of weekly ISU104 in combination with approved dose of CET is planned to further establish the clinical utility of ISU104.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
ISU Abxis Co., Ltd.
Funding
Korea Drug Development Fund.
Disclosure
S-B. Kim: Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Lilly; Advisory/Consultancy: Enzychem; Advisory/Consultancy: Dae Hwa Pharmaceutical Co. Ltd; Advisory/Consultancy: ISU Abxis; Advisory/Consultancy: Daiichi-Sankyo; Research grant/Funding (institution): Sanofi-Aventis; Research grant/Funding (institution): Kyowa-Kirin Inc; Research grant/Funding (institution): DongKook Pharm Co. B. Keam: Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy: MSD Oncology; Advisory/Consultancy: Genexin; Research grant/Funding (self): Ono Pharmaceutical; Research grant/Funding (self): MSD Oncology. K. Park: Advisory/Consultancy: Amgen; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: BluePrint; Advisory/Consultancy: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony: Boehringer Ingelheim; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Hanmi; Advisory/Consultancy: Loxo; Advisory/Consultancy: Merck KGaA; Advisory/Consultancy, Research grant/Funding (institution): MSD; Advisory/Consultancy: Ono Pharmaceutical; Advisory/Consultancy: Roche. T.M. Kim: Honoraria (institution), Advisory/Consultancy, Advisory/consultancy without any compensation: AstraZeneca; Honoraria (institution), Advisory/Consultancy, Advisory/consultancy without any compensation: Boryung; Honoraria (institution), Advisory/Consultancy, Advisory/consultancy without any compensation: Novartis; Honoraria (institution): Regeneron; Honoraria (institution), Advisory/Consultancy, Advisory/consultancy without any compensation: Sanofi; Honoraria (institution), Advisory/Consultancy, Advisory/consultancy without any compensation: Takeda; Honoraria (institution), Advisory/Consultancy, Advisory/consultancy without any compensation: Voronoi; Research grant/Funding (self): AstraZeneca-Khidi. S-B. Hong: Shareholder/Stockholder/Stock options, Full/Part-time employment: ISU Abxis. M-J. Ahn: Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Takeda; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Merck; Advisory/Consultancy: ONO; Advisory/Consultancy: BMS; Advisory/Consultancy: Novartis; Advisory/Consultancy: Alpha pharmaceutical; Advisory/Consultancy: Roche; Advisory/Consultancy: Progeneer. All other authors have declared no conflicts of interest.