# Phase I study of HFB200301, a First-in-Class TNFR2 agonist monoclonal antibody in patients with solid tumors # selected via Drug Intelligent Science (DIS™) # TPS2670 ## Presented at ASCO® June 3-7, 2022, Chicago, IL **Alexander I. Spira**¹**, Aung Naing**²**, Hani M. Babiker**³**, Mitesh J. Borad**⁴**, Elena Garralda**⁵**, Konstantinos Leventakos**⁶**, Peter John Oppelt**⁷**, Desamparados Roda**⁸**, Jon Zugazagoitia**⁹**, Christos Hatzis**¹⁰**, Margaret E. Chen**¹⁰**, Jinping Gan**¹⁰**, Andreas Raue**¹⁰**,** **Francisco Adrian**¹⁰**, Luigi Manenti**¹⁰**, Anthony B. El-Khoueiry**¹¹ ¹Virginia Cancer Specialists, Fairfax, VA; Department of Investigational Cancer Therapeutics, ²The University of Texas MD Anderson Cancer Center, Houston, TX; ³Mayo Clinic, Jacksonville, FL; Mayo Clinic, Phoenix, AZ; Vall d'Hebron Institute of 4 5 Oncology (VHIO), Barcelona, Spain; Mayo Clinic, Rochester, MN; ⁶ ⁷Washington University School of Medicine, Saint Louis, MO; ⁸Department of Medical Oncology, INCLIVA Biomedical Research Institute, University of Valencia, Instituto de Salud Carlos III, CIBERONC, Valencia, Spain; Hospital Clinico San Carlos, Madrid, Spain; ⁹ ¹⁰HiFiBiO Inc., Cambridge, MA; ¹¹University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, CA ## Therapeutic Hypothesis *HFB200301 stimulates TNFR2* *on tumor infiltrating T and NK* *cells to activate NK cells and* *enhance CD8+ T cell mediated* *anti-tumor response.*¹ *HFB200301 treatment (3 and 10 mg/kg, q3dx7) of MC38 bearing TNFR2 KI mice results in dose dependent* *antitumor activity (stasis) and improved survival compared to anti-PD-1 alone.*² ## HFB200301 - Humanized IgG1 mAb with sub-nM affinity for human TNFR2 with cyno cross-reactivity. - Enhanced and of conventional CD4+ and CD8+ effector T cells and robust activation of NK cells inactivation vitro and in the proliferation tumor microenvironment. - Single agent anti-tumor activity comparable to anti-PD-1 in syngeneic tumor models and prolonged survival in combination with anti-PD-1 compared to anti-PD-1 alone. ## DIS™ Selected Indications - Acceptable safety profile in GLP toxicological studies; favorable developability and pharmacokinetic (PK) profiles. **Rationale for indication selection based on DIS™** - Single-cell immune-profiling platform used to identify unique tumor-infiltrating T cell signatures - Focused on cytotoxic T lymphocytes as major component for HFB200301 activity using TNFR2-high and CD8A-high expression signature on The Cancer Genome Atlas dataset. - Preclinical biomarker signatures identified based on single cell analyses of ex vivo models³ will be validated from single-cell data from the Phase I study. ## Study Design # First-in-human, multicenter, open-label, dose escalation and dose expansion study ## Dose Escalation - Using modified Toxicity Probability Interval 2 (mTPI-2) design⁴ with target dose-limiting toxicity (DLT) rate of 30%. - At least 3 patients (up to 6) must be enrolled for dose escalation to occur. Back-filling cohorts is permitted. - Dosing 5 mg with provisional dose levels of 15, 50, 100, and initiated 150 mg at. - HFB200301 is administered as a 60-minute IV infusion every 4 weeks. - DLT period is the first 28 days after cycle 1 day 1 treatment. ## Dose Expansion - Expansions of up to 3 cohorts with up to 20 patients each. - EBV+ gastric cancer, PD-L1+ pleural mesothelioma, and clear cell renal cell carcinoma (ccRCC) cohorts may be initiated for. - Pending emerging data, additional patients with soft tissue sarcoma (STS), testicular germ cell tumors (TGCT), cutaneous melanoma, and PD-L1+ cancers including cervical cancer, lung adenocarcinoma, and head and neck squamous cell carcinoma (HNSCC). ## Key Eligibility Criteria - Male/female adult patients with histologically documented and advanced or metastatic solid tumors. Permitted tumor types: ➢ **Cutaneous melanoma** ➢ **ccRCC** ➢ **EBV+ gastric cancer** ➢ **Cervical cancer** ***PD-L1+ cancers*** ➢ **Lung adenocarcinoma** ➢ **Pleural mesothelioma** ➢ **TGCT** Additional cohort(s) - Patient must have measurable disease based on RECIST 1.1 (or mRECIST for mesothelioma). ➢ **HNSCC** ➢ **STS** *Other protocol defined inclusion criteria may apply.* - Patient cannot be using sensitive substrates of major cytochrome P450 enzymes. - Patient must be willing to undergo pre-treatment and on-treatment biopsies. - Patient cannot have hemoglobin <9.0 g/dL or equivalent. - Patient must have exhausted standard lines of systemic therapy.* ## Key Objectives ## Primary - Characterize safety and tolerability of single agent HFB200301 - Determine RDE(s) ## Secondary - Assess the PK profile and pharmacodynamic effects of HFB200301 - Determine biologically active dose(s) and anti-tumor efficacy of HFB200301 - Evaluate immunogenicity in the blood and tumor ## Exploratory - Assess relationship between PK, baseline and on treatment biomarkers, and/or anti-tumor efficacy - Immune modulation ## Enrollment | Enrollment opened | February 2022 | |-------------------|----------------| | Planned # US sites | 7 | | Planned # Spain sites | 3 | | Planned # China sites | 5 | | Planned # patients-Escalation | 30-60 | | Planned # patients-Expansion | 60-180 | ## References 1. Wei et al. AACR 2021; Poster #1883 2. Wei et al. AACR 2020; Poster #2282 3. Lee et al. AACR 2022; Poster #4732 4. Guo et al. *Contemp Clin Trials*. 2017;58:23-33 ## Acknowledgments We extend our thanks to the patients, their families, and the investigators and their site staff members who are making this trial possible. Thank you to Olja Rapaic, John Pallante, and Medpace, Inc. for their efforts and collaboration in this trial. This study is supported by HiFiBiO Inc. ## Contact Information This poster was presented at the 2022 American Society of Clinical Oncology Annual Meeting (June 3-7, 2022); Chicago, IL. Corresponding Author: aspira@nextoncology.com Clinicaltrials.gov Identifier: NCT05238883