1011P - Model-informed dose optimization of HFB200301, a TNFR2 agonist monoclonal antibody (mAb), in monotherapy and in combination with the anti-PD-1 mAb tislelizumab (TIS), in patients (pts) with advanced solid tumors

Background

Agonism of the TNF-alpha receptor TNFR2 enhances anti-tumor immunity by stimulating T cells and NK-cells in the tumor microenvironment. HFB200301 is a first-in-class anti-TNFR2 agonistic mAb, triggers both innate and adaptive immune stimulation. Based on clinical pharmacokinetics (PK) ngelheim and simulation, we explored 2 dosing regimens for HFB200301 to optimize its clinical benefit. We report a model-informed dose optimization of HFB200301 in monotherapy and in combination with TIS in pts with advanced refractory solid tumors.

Methods

Safety, preliminary efficacy, PK, and pharmacodynamics (PD) of HFB200301 dosed Q4W were investigated in a Phase 1 trial in monotherapy and combined with TIS. Initial monotherapy results were used to construct models and simulate various dosing regimens to optimize HFB200301 exposure and target engagement (TE). Subsequently, two Q2W dose cohorts in monotherapy and in combination with TIS were evaluated. Safety, PK, and PD data were collected at various timepoints, and radiographic responses were assessed every 8 weeks.

Results

Modeling and simulation results indicate administration of comparable doses of HFB200301 at more frequent intervals may provide a more favorable duration of TE and improve therapeutic outcome. As of April 14, 2024, 27 pts in monotherapy and 12 pts in combination received the Q4W dosing regimen, and 5 pts in monotherapy and 1 pt in combination received the Q2W dosing regimen. No dose limiting toxicities nor differences in treatment-related adverse events (TRAEs) were observed in any treatment arm. Emerging data indicates sustained TE with more frequent dosing may provide more favorable clinical outcomes as evidenced by tumor reduction in a HNSCC patient receiving monotherapy HFB200301 Q2W.

Conclusions

Model-optimized dosing of HFB200301 may provide improved therapeutic activity while maintaining a favorable safety profile in pts with advanced solid tumors. Further dose evaluation is underway with HFB200301 as a monotherapy and in combination with TIS.

Clinical trial identification

NCT05238883.

Editorial acknowledgement

Legal entity responsible for the study

HiFiBiO Therapeutics Inc.

Funding

HiFiBiO Therapeutics Inc.

Disclosure

J. Zugazagoitia: Financial Interests, Personal, Invited Speaker: Takeda, BMS, AstraZeneca, NanoString, Guardant Health; Financial Interests, Personal, Advisory Board: Roche, Sanofi, BMS, Pfizer, Novartis; Financial Interests, Personal and Institutional, Funding, Research Grant: AstraZeneca, Roche, BMS. E. Garralda: Financial Interests, Personal, Invited Speaker: MSD, Roche, Thermo Fisher, Novartis, SeaGen; Financial Interests, Personal, Advisory Board: Roche, Ellipses Pharma, Boehringer Ingelheim, Janssen Global Services, Seattle Genetics, Thermo Fisher, MabDiscovery, Anaveon, Hengrui, F-Star Therapeutics, Sanofi, Incyte, Medscape; Financial Interests, Personal, Full or part-time Employment: NEXT Oncology; Financial Interests, Personal, Stocks/Shares: 1TRIALSP; Financial Interests, Institutional, Funding: Novartis, Roche, Thermo Fisher, AstraZeneca, Taiho; Financial Interests, Institutional, Research Grant: BeiGene, Janssen. A.I. Spira: Financial Interests, Personal, Other, Consulting or Advisory Role: Incyte, Mirati Therapeutics, Gritstone Oncology, Jazz Pharmaceuticals, Janssen Research & Development, Mersana, Gritstone Bio, Daiichi Sankyo/AstraZeneca, Array Biopharma, Blueprint Medicines, Regeneron, Lilly, Black Diamond Therapeutics, Sanofi; Financial Interests, Personal, Other, Consulting or Advisory Role / Honoraria: Amgen, Novartis, Takeda, AstraZeneca/MedImmune, Merck, Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: CytomX Therapeutics, Janssen Oncology, Bayer; Financial Interests, Institutional, Officer, CEO: NEXT Oncology Virginia; Financial Interests, Personal, Stocks/Shares: Eli Lilly; Financial Interests, Institutional, Local PI: LAM Therapeutics, Roche, AstraZeneca, Boehringer Ingelheim, Astellas Pharma, MedImmune, Novartis, Newlink Genetics, Incyte, AbbVie, Ignyta, Trovagene, Takeda, Macrogenics, CytomX Therapeutics, Astex Pharmaceuticals, Bristol Myers Squibb, Loxo, Arch Therapeutics, Gritstone, Plexxikon, Amgen, Daiichi Sankyo, ADCT, Janssen Oncology, Mirati Therapeutics, Rubius, Synthekine, Mersana, Blueprint Medicines, Kezar, Revolution Med, Regeneron, Loxo, Alkermes, Medikine, Black Diamond Therapeutics, Nalo Therapeutics, Scorpion Therapeutics, Arrivent Biopharma. A.B. El-Khoueiry: Financial Interests, Personal, Advisory Board: Exelixis, AstraZeneca, Genentech, Agenus, Tallac, ABL Bio, Senti Biosciences, Qurient; Financial Interests, Institutional, Funding: Fulgent, Astex, AstraZeneca; Financial Interests, Personal, Steering Committee Member: Merck; Financial Interests, Personal, Coordinating PI: Genentech; Financial Interests, Institutional, Coordinating PI, trial; funding: Auransa; Non-Financial Interests, Principal Investigator: Agenus, Affimed, Bayer. Y. Zhao: Financial Interests, Personal, Invited Speaker: Cahon, Total Health; Financial Interests, Personal, Other, consultation: keyquest, windrose; Financial Interests, Institutional, Local PI: GI Innovation Inc, AstraZeneca, Incagn, Mirati Therapeutics, PDS Biotechnology, Alpine Immune Science. P. Oppelt: Financial Interests, Institutional, Local PI: HiFiBio. X. Lin, S. Xie: Financial Interests, Personal, Full or part-time Employment: HiFiBio Therapeutics. M. Chen: Financial Interests, Institutional, Full or part-time Employment: HiFiBiO Therapeutics, Inc. J. Gan: Financial Interests, Personal, Full or part-time Employment: HiFiBiO Therapeutics; Financial Interests, Personal, Stocks/Shares: HiFiBiO Therapeutics. J. Russella Pollard: Financial Interests, Personal, Full or part-time Employment, Employer: HiFiBio; Financial Interests, Personal, Stocks/Shares, Share Options: HiFiBio; Financial Interests, Personal, Stocks/Shares, Shares: Moderna, Sanofi. W. Hedrich: Financial Interests, Institutional, Full or part-time Employment: HiFiBiO Therapeutics, Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. J. Pallante: Financial Interests, Personal, Full or part-time Employment, Role is Sr. Vice President, Clinical Operations and Quality Mgmt.: HiFiBiO Therapeutics; Financial Interests, Personal, Stocks/Shares: HiFiBiO Therapeutics. L. Schweizer: Financial Interests, Personal, Officer: HiFiBiO Therapeutics; Financial Interests, Personal, Stocks/Shares: HiFiBiO Therapeutics. R.H.I. Andtbacka: Financial Interests, Personal, Full or part-time Employment: HiFiBiO Therapeutics, Seven and Eight BioPharmaceuticals Inc.; Financial Interests, Personal, Stocks/Shares: HiFiBiO Therapeutics, Seven and Eight BioPharmaceuticals Inc. All other authors have declared no conflicts of interest.