A Study of HFB200301 in Adult Patients With Advanced Solid Tumors

Primary Outcome Measures

1. Number of participants with adverse events (AEs), serious AEs (SAEs), dose-limiting toxicities (DLTs), changes in laboratory values, vital signs and electrocardiogram (ECG) [ Time Frame: Cycle 1 Day 1 to 30 days after the last dose of HFB200301 (each cycle is 28 days), assessed up to 3 years ]
2. To determine a Recommended Phase 2 Dose (RP2D) during Dose Expansion [ Time Frame: Cycle 1 Day 1 to 30 days after the last dose of HFB200301 (each cycle is 28 days), assessed up to 3 years ]

Secondary Outcome Measures

1. Objective Response Rate (ORR) as determined by (modified) Response Evaluation Criteria in Solid Tumors [(m)RECIST] 1.1 and immune-RECIST (iRECIST) [ Time Frame: Baseline to 30 days after the last dose of HFB200301 (each cycle is 28 days), assessed up to 3 years ]
2. Disease Control Rate (DCR) as determined by (m)RECIST 1.1 and iRECIST [ Time Frame: Baseline to 30 days after the last dose of HFB200301 (each cycle is 28 days), assessed up to 3 years ]
3. Duration of Response (DOR) as determined by (m)RECIST 1.1 and iRECIST [ Time Frame: Start of first response to first date of disease progression, clinical progression or death, whichever occurs first, assessed up to 3 years ]
4. Progression Free Survival (PFS) as determined by (m)RECIST 1.1 and iRECIST [ Time Frame: Baseline to disease progression or death, whichever occurs first, assessed up to 3 years ]
5. Minimum serum concentration (Cmin) [ Time Frame: Cycle 1 Day 1 to day of the last dose of HFB200301 (each cycle is 28 days), through study completion, an average of 3 year ]
6. Maximum serum concentration (Cmax) [ Time Frame: Cycle 1 Day 1 to day of the last dose of HFB200301 (each cycle is 28 days), through study completion, an average of 3 year ]
7. Area under the concentration versus time curve (AUC) [ Time Frame: Cycle 1 Day 1 to day of the last dose of HFB200301 (each cycle is 28 days), through study completion, an average of 3 year ]
8. Terminal half-life (T1/2) [ Time Frame: Cycle 1 Day 1 to day of the last dose of HFB200301 (each cycle is 28 days), through study completion, an average of 3 year ]
9. Serum concentration for measurement of anti-HFB200301 antibodies [ Time Frame: Cycle 1 Day 1 to day of the last dose of HFB200301 (each cycle is 28 days), through study completion, an average of 3 year ]
10. To assess the pharmacodynamic (PD) effects of HFB200301 in the blood and in the tumor [ Time Frame: Cycle 1 Day 1 to Cycle 3 Day 2 (each cycle is 28 days) ]
    Percent change in immunologic changes to immune cells in the blood and tumor

Other Outcome Measures

1. AUC vs percent of Tcell changes in the blood [ Time Frame: Cycle 1 Day 1 to Cycle 4 Day 1 (each cycle is 28 days) ]
2. AUC vs percent of Tcell changes in the tumor [ Time Frame: Cycle 1 Day 1 to Cycle 4 Day 1 (each cycle is 28 days) ]
3. AUC vs percent change in tumor size [ Time Frame: Cycle 1 Day 1 to Cycle 4 Day 1 (each cycle is 28 days) ]
4. Percent Tcell changes in the blood vs percent change in tumor size [ Time Frame: Cycle 1 Day 1 to Cycle 4 Day 1 (each cycle is 28 days) ]
5. Percent Tcell changes in the tumor vs percent change in tumor size [ Time Frame: Cycle 1 Day 1 to Cycle 4 Day 1 (each cycle is 28 days) ]

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 3 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
• 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
• 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 2 weeks of the first dose of study drug
• History or presence of drug or non-drug induced interstitial lung disease or pneumonitis ≥Grade 2
• 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