Abstract 887P
Background
Following a dose-escalation study, a dose-expansion study for ISU104 (monotherapy and combination therapy with CET) has been conducted in R/M HNSCC (Ann Oncol, abst #928P, 2020). Here we report updated final safety, clinical efficacy and biomarker analysis results from the dose-expansion study.
Methods
Eighteen R/M HNSCC pts excluding nasopharyngeal cancer, were enrolled and allocated to Mono (ISU104, 20 mg/kg/day, Q3W; N=6) or Combo groups (ISU104 20 mg/kg, Q3W and CET, initially 400 mg/m2 followed by 250 mg/m2, Q1W; N=12). Tumor response assessments (RECIST 1.1), safety and occurrence of anti-drug antibodies (ADA) were determined. Immunohistochemistry, RNAscope® Assay-based in situ hybridization (ISH) and next generation sequencing were performed on sections of biopsy samples.
Results
Most common treatment emergent adverse events (AEs) included decreased appetite (66.7%) and stomatitis (50%) in Mono, and diarrhea (75.0%) and dermatitis acneiform (50%) in Combo. Serious AEs were reported 16.7% in Mono and 58.33% in Combo, but no AEs led to treatment discontinuation. One patient (1/18, 5.56%) developed ADA, which did not have neutralizing activity. Four pts in Combo were responsive to treatment (1 CR and 3 PR out of 11 analyzed pts; 36.36%); one patient remained CR up to now. Duration of responses were 46, 62, 163+ and 449+ days in Combo, and median progression-free survival was 54 and 99 days in Mono and Combo groups, respectively, in median follow-up period of 480 days (as of 30th April 2021). H-scores of potential biomarkers including EGFR-ISH at pre-treatment were correlated with tumor size changes following combination therapy. Potential implication of TP53 mutations and EGFR amplification in patient selection was also noted.
Conclusions
ISU104 alone or in combination with CET were safe and tolerable in R/M HNSCC pts. Encouraging clinical efficacies and potential biomarkers were demonstrated from combination therapy. A phase II study of ISU104 (Q3W, 20 mg/kg/day) in combination with CET (Q1W) is planned to further strengthen the clinical utility of ISU104.
Clinical trial identification
NCT03552406.
Editorial acknowledgement
Legal entity responsible for the study
ISU ABXIS Co. LTD.
Funding
ISU ABXIS Co. LTD.
Disclosure
S. Kim: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Dae Hwa Pharmaceutical Co. Ltd; Financial Interests, Personal, Advisory Board: ISU Abxis; Financial Interests, Personal, Advisory Board: Daiichii-Sankyo; Non-Financial Interests, Institutional, Member of the Board of Directors: KSMO; Non-Financial Interests, Institutional, Member of the Board of Directors: KCA; Financial Interests, Personal, Stocks/Shares: Genopeaks; Financial Interests, Personal, Stocks/Shares: Neogene TC; Financial Interests, Institutional, Funding: Novartis; Financial Interests, Institutional, Funding: Sanofi-Aventis; Financial Interests, Institutional, Funding: DongKook Pharm Co; Non-Financial Interests, Personal and Institutional, Principal Investigator: LEO (IIT); Non-Financial Interests, Personal, Member: ASCO; Non-Financial Interests, Personal, Member: ESMO; Non-Financial Interests, Personal, Member: KSMO. B. Keam: Non-Financial Interests, Personal, Invited Speaker: AstraZeneca; Non-Financial Interests, Personal, Invited Speaker: Merck; Non-Financial Interests, Personal, Invited Speaker: MSD oncology; Non-Financial Interests, Personal, Advisory Board: ABL Bio; Non-Financial Interests, Personal, Advisory Board: AstraZeneca; Non-Financial Interests, Personal, Advisory Board: CbsBioscience; Non-Financial Interests, Personal, Advisory Board: Genexine; Non-Financial Interests, Personal, Advisory Board: Handok; Non-Financial Interests, Personal, Advisory Board: Merck; Non-Financial Interests, Personal, Advisory Board: MSD Oncology; Non-Financial Interests, Personal, Advisory Board: TrailInformatics; Non-Financial Interests, Personal, Funding: AstraZeneca; Non-Financial Interests, Personal, Funding: MSD Oncology; Non-Financial Interests, Personal, Funding: Ono Pharmaceutical. K. Park: Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: BluePrint; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: Hanmi; Financial Interests, Personal, Advisory Board: LOXO; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Ono Pharmaceutical; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Funding: AstraZeneca; Financial Interests, Personal, Funding: MSD. T.M. Kim: Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Boryung; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Invited Speaker: Regeneron; Financial Interests, Institutional, Invited Speaker: Sanofi; Financial Interests, Institutional, Invited Speaker: Takeda; Financial Interests, Institutional, Invited Speaker: Voronoi; Non-Financial Interests, Personal, Advisory Board: AstraZeneca; Non-Financial Interests, Personal, Advisory Board: Boryung; Non-Financial Interests, Personal, Advisory Board: Novartis; Non-Financial Interests, Personal, Advisory Board: Sanofi; Non-Financial Interests, Personal, Advisory Board: Takeda; Non-Financial Interests, Personal, Advisory Board: Voronoi; Financial Interests, Personal, Funding: AstraZeneca. S. Hong: Financial Interests, Institutional, Full or part-time Employment: ISU Abxis; Financial Interests, Personal, Stocks/Shares: ISU Abxis; Financial Interests, Institutional, Funding: KHIDI; Financial Interests, Personal, Invited Speaker: National Institute of Mathematical Sciences; Financial Interests, Personal, Invited Speaker: Human Asia. M. Ahn: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: ONO; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: ONO; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Alpha pharmaceuticals; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: Roche. All other authors have declared no conflicts of interest.