A Phase 1a/1b, Open-Label, Multi-Center, Dose Escalation and Expansion Study of HFB200301 (TNFR2 Agonist Antibody) as a Single Agent and in Combination With Tislelizumab (Anti-PD-1 Antibody) in Adult Patients With Advanced Solid Tumors

More details:

Overview

HFB200301, also known as HFB2003, is an investigational monoclonal antibody developed by HiFiBiO Therapeutics. It targets tumor necrosis factor receptor 2 (TNFR2) and is being evaluated for the treatment of advanced solid tumors.

Mechanism of Action

HFB200301 functions as an agonist to TNFR2, a receptor expressed on various immune cells, including CD4+ and CD8+ T cells, as well as natural killer (NK) cells. By activating TNFR2, HFB200301 enhances the proliferation and activation of these effector cells within the tumor microenvironment, potentially leading to improved anti-tumor responses. Notably, this activation occurs without affecting regulatory T cell (Treg) numbers, which are often associated with immunosuppression in tumors. (aacrjournals.org)

Clinical Development

A Phase I clinical trial (NCT05238883) is underway to assess the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of HFB200301, both as a monotherapy and in combination with tislelizumab, an anti-PD-1 monoclonal antibody. The trial includes adult patients with advanced solid tumors. (ascopubs.org)

Efficacy

Preliminary data from the ongoing Phase I trial indicate that HFB200301 exhibits anti-tumor activity. Early response evaluations have shown durable clinical responses exceeding six months in patients with PD-L1 positive pleural mesothelioma and Epstein-Barr virus-positive gastric cancer who received the combination therapy. (ascopubs.org)

Safety

HFB200301 has demonstrated a favorable safety profile in the Phase I trial. No dose-limiting toxicities have been observed in either the monotherapy or combination therapy cohorts. Treatment-related adverse events (TRAEs) occurred in 44% of monotherapy patients and 50% of combination therapy patients. The most common TRAEs included pruritus (11%), tremor (7%), fatigue (7%), asthenia (7%), and nausea (7%). Importantly, no Grade 3 or higher TRAEs were reported, and no patients discontinued treatment due to TRAEs. (ascopubs.org)

Further Reading

• Mechanism of Action and Biomarker Strategy for HFB200301
• Phase I Dose Escalation Trial of HFB200301

Last updated: Apr 2025

Inclusion Criteria:

* Previously received the following lines of systemic therapy for the advanced/metastatic disease:

* Gastric cancer: at least 2 lines of therapy

* Renal cell carcinoma: at least 2 lines of therapy

* Melanoma:

* BRAF V600E mutant: must have received at least 2 lines of therapy

* BRAF V600E wild type: must have received at least 1 line of therapy

* Sarcoma: at least 1 line of therapy

* Testicular germ cell tumor: at least 2 lines of therapy

* Cervical cancer: at least 2 lines of therapy

* Mesothelioma: at least 2 lines of therapy

* Non-small cell lung cancer: at least 2 lines of therapy

* Head and neck squamous cell carcinoma: at least 2 lines of therapy

* Suitable site to biopsy at pre-treatment and on-treatment

* Measurable disease as determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or modified RECIST (mRECIST) for mesothelioma

* Eastern Cooperative Oncology Group performance status of 0 or 1

Exclusion Criteria:

* Systemic anti-cancer therapy within 2 weeks prior to start of study drug or within 4 weeks for immune-oncologic therapy

* For soft tissue sarcoma and testicular germ cell tumor patients only: prior immune therapy

* Therapeutic radiation therapy within the past 2 weeks

* Prior exposure to agents targeting the Tumor Necrosis Factor Receptor type 2 (TNFR2) receptor

* Active autoimmune disease requiring systemic treatment in the previous 2 years

* Systemic steroid therapy (\>10 mg/day of prednisone or equivalent) or any immune suppressive therapy ≤ 14 days before first dose

* Persisting toxicity of ≥Grade 2 (≥Grade 1 for diarrhea) relating to prior anti cancer therapy with the following exceptions:

* All grades of alopecia are acceptable

* Endocrine dysfunction on replacement therapy is acceptable

* Severe or unstable medical condition, including uncontrolled diabetes, coagulopathy, or unstable psychiatric condition

* Major surgery within 4 weeks of the first dose of study drug

* History or presence of drug or non-drug induced interstitial lung disease or pneumonitis ≥Grade 2. For combination only: non-small cell lung cancer patients, mesothelioma or patients with significantly impaired pulmonary function or who require supplemental oxygen at baseline must undergo an assessment of pulmonary function at screening

* History of allergic reactions, immune related reactions, or cytokine release syndrome (CRS) attributed to compounds of similar chemical or biologic composition to monoclonal antibodies or any excipient of HFB200301

* Using sensitive substrates of major cytochrome P450 (CYP450) enzymes

* Known active malignancy, with the exception of the specific cancer under investigation in this trial, that required treatment within the previous 2 years

* For combination only:

* Prior randomization in a tislelizumab study regardless of the treatment arm, until the primary and key secondary endpoints of the study have read out

* Hypersensitivity to tislelizumab or any of its excipients.