A Study of HFB200301 as a Single Agent and in Combination With Tislelizumab in Adult Patients With Advanced Solid Tumors

This is a Phase 1a/1b, first in human, open-label, dose escalation and expansion study in adults with advanced cancers. The study will comprise of

• A Screening Period
• A Treatment Period during which participants will receive the study drug on the first day of each cycle
• A Follow-up Period

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.