Patient must have the ability to understand and voluntarily sign a written informed consent form (ICF) and willingness and ability to comply with all protocol requirements. If consent cannot be obtained in writing, it must be documented and witnessed.
Patient must have signed informed consent prior to any study procedure.
Patient must be male or non-pregnant/non-lactating female (a negative serum pregnancy test at Screening is mandatory) ≥ 18 years of age.
Patient must have histologically documented and advanced or metastatic solid tumors. The following tumor types are permitted:
EBV+ gastric cancer as determined on archival material by in situ hybridization or other institutional standard based on local laboratory data;
Clear cell renal cell carcinoma;
Cutaneous melanoma;
Soft tissue sarcoma;
Testicular germ cell tumors;
PD-L1+ cancers (combined positive score [CPS] or tumor positive score [TPS] ≥ 1 or PD-L1-stained, tumor-infiltrated immune cells of any intensity covering ≥ 1% of the
tumor area) as determined by an FDA-approved test on an archival tumor specimen based on local, available laboratory data. The following tumor types are permitted:
Cervical cancer;
Pleural mesothelioma;
Lung adenocarcinoma;
Head and neck squamous cell carcinoma with a primary site of the oral cavity, oropharynx, larynx, or hypopharynx.
Patient must have previously received the following lines of systemic therapy for the advanced/metastatic disease:
EBV+ gastric cancer: Patient must have received at least 2 lines of therapy (but no more than 4) including fluoropyrimidine, platinum-based regimens, and anti-PD-1/PD-L1 inhibitors as a single agent or in combination. HER-2+ patients must have received an anti-HER-2 treatment;
Clear cell renal cell carcinoma: at least 2 lines of therapy (but no more than 3) such as vascular endothelial growth factor (VEGF) tyrosine kinase inhibitors (TKIs), mammalian target of rapamycin (mTOR) inhibitors, or anti-PD-1/PD-L1 inhibitors as single agents or in combination;
Cutaneous melanoma:
BRAF V600E mutant: Patient must have received at least 2 lines of therapy (but no more than 3) including anti-PD-1/PD-L1 inhibitors as single agents or in combination (such as anti-CTLA-4 therapy) and BRAFV600E inhibitor therapy either as a single agent or in combination with a MEK inhibitor;
BRAF V600E wild type: Patient must have received at least 1 line of therapy (but no more than 2) including anti-PD-1/PD-L1 inhibitors as single agents or in combination (such as anti-CTLA-4 therapy).
Soft Tissue Sarcoma: at least 1 line of Standard of Care therapy (but no more than 2);
Testicular germ cell tumor: at least 2 lines of Standard of Care therapy (but no more than 3);
PD-L1+ cervical cancer: at least 2 lines of therapy (but no more than 3) including bevacizumab in combination with chemotherapy and an anti-PD-1 inhibitor as a single agent or in combination;
PD-L1+ pleural mesothelioma: at least 2 lines of therapy (but no more than 3) including platinum-based regimens and an anti-PD-1 inhibitor as a single agent or in combination;
PD-L1+ non-small cell lung cancer adenocarcinoma: at least 3 lines of therapy (but no more than 4) including platinum-based regimens and anti-PD-1/PD-L1 inhibitors. Patients with known oncogenic driver alterations must have failed TKIs;
PD-L1+ head and neck squamous cell carcinoma: at least 2 lines of therapy (but no more than 3 systemic therapies) including platinum-based regimens, epidermal growth factor receptor (EGFR) inhibitors (eg, cetuximab), or anti-PD-1/PD-L1 inhibitors as single agents or in combination.
Patient must have a site suitable to biopsy according to the treatment institution’s guidelines. Patient must be willing to undergo pre-treatment and on-treatment biopsies.
Patient must have measurable disease, defined as at least 1 lesion measured in at least 1 dimension by computed tomography (CT) scan, magnetic resonance (MR) imaging, or calipers by clinical exam as determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or modified RECIST (mRECIST) for mesothelioma.
Patient has an Eastern Cooperative Oncology Group performance status of 0 or 1.
Patient received systemic anti-cancer therapy within 2 weeks prior to start of study drug. For cytotoxic agents with major delayed toxicity (e.g., mitomycin C), 6 weeks of washout are mandated.
For soft tissue sarcoma and testicular germ cell tumor patients only: Patient received prior immune therapy; e.g., targeting PD-1, PD-L1, CTLA-4, or immune agonist antibodies.
Patient received therapeutic radiation therapy within the past 2 weeks (palliative radiotherapy to a limited field is allowed).
Patient received prior exposure to agents targeting the TNFR2 receptor.
Patient has an active autoimmune disease requiring systemic treatment in the previous 2 years.
Note: This includes patients with a history of inflammatory bowel disease, ulcerative colitis and Crohn’s Disease, rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythematosus, autoimmune vasculitis (e.g., Wegener’s granulomatosis), central nervous system (CNS) or motor neuropathy considered of autoimmune origin (e.g., Guillain Barré Syndrome, myasthenia gravis, multiple sclerosis), and moderate or severe psoriasis. However, patients with rheumatoid arthritis or psoriasis in stable remission for at least 6 months and without contraindications to possible co-treatment with corticosteroids for immune-related adverse events, vitiligo, Sjogren’s syndrome, interstitial cystitis, Graves’or Hashimoto’s disease, or hypothyroidism stable on hormone replacement are permitted.
Patient has laboratory values (indicating organ and bone marrow dysfunction) defined as:
Absolute neutrophil count ≤ 1.0 × 10^9/L;
Platelet count ≤ 100 × 10^9/L;
Hemoglobin < 9.0 g/dL or equivalent. Criteria must be met without packed red blood cell transfusion within the prior 2 weeks. Patients can be on a stable dose of erythropoietin (≥ 3 months);
Total bilirubin > 1.5 × upper limit of normal (ULN) or > 3.0 × ULN unless known Gilbert syndrome has been diagnosed;
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) > 3.0 × ULN;
Serum creatinine > 1.5 × ULN or creatinine clearance < 40 mL/min using Cockcroft-Gault formula.
Patient received systemic steroid therapy (> 10 mg/day of prednisone or equivalent) or any immune suppressive therapy. Replacement-dose steroids for managing adrenal insufficiency within 7 days of first study treatment and non-systemic steroids; topical, intraocular, intranasal, intra-articular, or inhalation steroids are allowed.
Patient has persisting toxicity of ≥ Grade 2 (≥ Grade 1 for diarrhea) NCI CTCAE version 5.0 relating to prior anti-cancer therapy with the following exceptions:
Patient has symptomatic or uncontrolled CNS metastases, leptomeningeal carcinomatosis, or untreated spinal cord compression requiring concomitant treatment such as surgery, radiation, or steroids (≥ 10 mg/day of prednisone or equivalent);
Patient has severe or unstable cardiac conditions including, but not limited to, the following:
Congestive heart failure (New York Heart Association Class III or IV);
Uncontrolled hypertension;
Uncontrolled cardiac arrhythmia requiring medication (≥ Grade 2 according to NCI CTCAE version 5.0);
Myocardial infarction within 6 months prior to starting study drug, or any other significant or unstable concurrent cardiac illness;
Congenital long QTcF interval > 470 msec at Screening.
Patient has severe or unstable medical condition, including uncontrolled diabetes, coagulopathy (where the Investigator considers interruption of anticoagulation for biopsies as high risk), or unstable psychiatric condition;
Patient had major surgery within 2 weeks of the first dose of study drug;
Patient has known infections, including the following:
Human immunodeficiency virus, hepatitis B virus (HBV) (i.e., hepatitis B surface antigen positive), or hepatitis C virus (HCV) (i.e., detectable HCV RNA);
Active infections requiring systemic therapy (including asymptomatic infections with positive virus titers and the Investigator’s judgment that worsening of the condition is likely with study drug or the condition would impair or prohibit a patient’s participation in the study).
Patient has received a live vaccine within 30 days prior to the first dose of study drug. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations should not be administered within ±14 days of HFB200301 infusion
Patient has a history or presence of drug or non-drug induced interstitial lung disease or pneumonitis ≥ Grade 2;
Patient has a 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.
Patient is using sensitive substrates of major cytochrome P450 (CYP450) enzymes.
Patient has a known active malignancy, with the exception of the specific cancer under investigation in this trial, that required treatment within the previous 2 years. Exceptions include basal or squamous cell skin cancer, superficial bladder cancer, or other tumors that,in the opinion of the Investigator, should not impact life expectancy.
If patient is a woman of childbearing potential, defined as a woman physiologically capable of becoming pregnant, she must use a highly effective method of contraception during treatment and for 3 months following the last dose of study drug. Highly effective methods of contraception are highly effective birth control methods with a failure rate of < 1% per year when used consistently and correctly, including:
Combined estrogen- and progestin-containing hormonal contraception associated with inhibition of ovulation given orally, intravaginally, or transdermally; progestin-only hormonal contraception associated with inhibition of ovulation given orally, by injection, or by implant; intrauterine devices; and intrauterine hormone-releasing systems;
Female sterilization (surgical bilateral oophorectomy with/without hysterectomy, total hysterectomy, bilateral tubal occlusion/ligation) at least 6 weeks before study treatment;
Male sterilization (at least 6 months prior to first study treatment dose);
Complete sexual abstinence. Periodic abstinence (e.g., calendar) and withdrawal are not acceptable. Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study drug. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the patient.
If patient is male able to father children, he must agree to use 2 acceptable methods of contraception throughout the study (e.g., condom plus spermicidal gel). Sperm donation is prohibited during the duration of participation in this study and for 30 days after the last dose of study drug.