A Dose Escalation Study of HFB301001 in Adult Patients with Advanced Solid Tumors

Overview

About this study

The purpose of this study is to characterize the safety and tolerability of single agent HFB301001 and to determine recommended dose expansino (RDE(s) and a recommended Phase 2 dose (RP2D).

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • 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 advanced or metastatic solid tumors of soft tissue sarcoma, renal cell carcinoma, uterine carcinosarcoma, hepatocellular carcinoma, or 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:
    • Soft tissue sarcoma: at least 1 line of therapy (but no more than 2);
    • Renal cell carcinoma: must have received at least 2 lines of therapy (but no more than 4) including an anti-PD-1/PD-L1 inhibitor as single agent or in combination;
    • Uterine carcinosarcoma: not amenable to surgical resection and/or radiation therapy and at least 1 line of therapy (but no more than 2). Patients with known oncogenic driver alterations or MSI-high or TMB-high tumors should have received target therapies or anti-PD-1/L-1 inhibitors respectively;
    • Hepatocellular carcinoma: at least 1 line of therapy (but no more than 2 systemic therapies) including anti-PD-1/PD-L1 inhibitors as single agent or in combination or multi-TKI/VEGF/VEGF receptor 2 (VEGFR2) inhibitors;
    • Head and neck squamous cell carcinoma: must have received at least 2 lines of therapy (but no more than 3 systemic therapies) including a platinum containing regimen and an anti-PD-1/PD-L1 inhibitor (either concurrently or sequentially)
  • 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 RECIST 1.1 and iRECIST; Patient has an Eastern Cooperative Oncology Group performance status of 0 or 1.

Exclusion Criteria:

  • 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 uterine carcinosarcoma patients only:
    • Patient received prior immune therapy; e.g., targeting PD-1, PD-L1, cytotoxic T-lymphocyte associated protein 4 (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 OX40 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 function) defined as:
    • Absolute neutrophil count < 1.0 × 10^9/L;
    • Platelet count < 100 × 10^9/L (< 75 × 10^9/L for hepatocellular carcinoma);
    • 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;
    • 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 1 National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 relating to prior anti-cancer therapy with the following exceptions:
    • All grades of alopecia are acceptable;
    • Endocrine dysfunction on replacement therapy is acceptable. 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); Note: Patients are eligible if neurologic symptoms and CNS imaging are stable for 14 days prior to the first dose of study drug and do not require systemic steroids (> 10 mg/day of prednisone or equivalent) for symptom control.
  • 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).
      • Note: Patients with a prior history of HBV infection who are surface antigen negative (treated/untreated) or patients with a prior history of treated HCV infection who are HCV RNA undetectable may be enrolled.
    • Patients whose disease is controlled under antiviral therapy should not be excluded;
    • 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 14 days prior to the first dose of study drug. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations should not be administered within ± 7 days of HFB301001 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 attributed to compounds of similar chemical or biologic composition to monoclonal antibodies or any excipient of HFB301001.
  • 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 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.

Eligibility last updated 8/30/21. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Mitesh Borad, M.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Jacksonville, Fla.

Mayo Clinic principal investigator

Hani Babiker, M.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Rochester, Minn.

Mayo Clinic principal investigator

Konstantinos Leventakos, M.D., Ph.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available
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