MC# 21-22 - A Phase I/II randomized, double-blind, placebo-controlled trial examining XB2001 (anti-IL-1⍺ True Human antibody) in combination with ONIVYDE + 5-FU/LV (+folinic acid) in advanced pancreatic cancer

  • Agent(s): XB2001
  • Disease Type(s): Pancreatic
  • Phase(s): I, II
  • Drug Classification(s): Targeted Therapy, Monoclonal Antibody
  • Molecular Target(s): IL-1α

Mechanism of Action

XB2001 is a recombinant human IgG4 monoclonal antibody specific for human interleukin-1⍺ (IL-1⍺).  IL-1⍺ induces upregulation of VEGF and angiogenesis in the tumor microenvironment; IL-1⍺ also acts to recruit infiltration by leukocytes (such as myeloid suppressor cells) that can suppress anti-tumor immunity.

Purpose

In this study, the sponsor and investigators want to learn:

  • About the safety and tolerability of XB2001 in combination with chemotherapy treatment
  • How proteins that indicate the status of your disease are affected with use of XB2001
  • If XB2001 prevents or delays tumor growth or shrinks existing tumors
  • How much of XB2001 is absorbed into the blood and how fast it is removed
Inclusion Criteria
  1. Written informed consent provided by the patient
  2. Age ≥18 years
  3. Histologically or cytologically confirmed pancreatic adenocarcinoma of exocrine pancreas that is metastatic, unresectable, or recurrent
  4. At least one measurable lesion according to Response Evaluation Criteria in Solid Tumor (RECIST v1.1)
  5. Documented disease progression after one prior gemcitabine-based therapy OR one FOLFIRINOX and gemcitabine combination therapy
  6. Eastern Cooperative Oncology Group (ECOG) performance of 0 or 1 or Karnofsky performance status (KPS) ≥ 70
  7. Adequate hepatic, renal and bone marrow function within 4 weeks prior to registration defined as:
    • Serum total bilirubin ≤ upper normal limit (UNL)
    • Serum albumin ≥ 3.0 g/dL
    • Aspartate aminotransferase (AST) & alanine aminotransferase (ALT) ≤ 3 x UNL (≤ 5 x UNL is acceptable if liver metastases are present)
    • CLcr > 30 ml/min (calculated by Cockcroft-Gault method)
    • Leukocytes ≥ 3000/mL
    • Absolute neutrophil count ≥ 1500 mm3
    • Platelets ≥ 100,000 mm3; must not have had transfusion in the prior 2 weeks
    • Hemoglobin ≥ 9 g/dL; must not have had transfusion in the prior 2 weeks
  8. Full understanding of the study protocol procedures and willingness to comply with them
  9. Normal ECG or ECG without any clinically significant findings with QTc < 470 ms
  10. For women of childbearing potential (WOCBP), a negative serum pregnancy test result at Screening
  11. In case of female subjects of childbearing potential, willingness to use one method of contraception of high efficacy during the entire study period.  These methods can include but not limited to hormonal contraceptives, intrauterine devices, condoms, diaphragms etc.  Women of non-childbearing potential include those considered to have a medical history that indicates that pregnancy is not a reasonable risk, including post-menopausal women and those with a history of hysterectomy or surgically sterilized. 
  12. If you are a male participating in this clinical reserach study, you should not get a sexual partner pregnant during your participation in this research study as the effect of the research drug on sperm is not known.  The male contraception methods can include but not limited to mechanical methods (abstinence, withdrawal, non-vaginal intercourse) or contemporary methods comprising condoms and vasectomy.
  13. At least 14 days since the last cancer treatment including: chemotherapy, radiation therapy, surgery, hormonal therapy prior to baseline visit
Exclusion Criteria
  1. History of treatment with XB2001 for any reason
  2. Clinically significant GI disorders
  3. Severe arterial thromboembolic events less than 6 months before inclusion
  4. Severe hypersensitivity to 5-FU
  5. Use of warfarin within 4 weeks of screening or any time during the study
  6. Prior Whole Brain Radiation Therapy (WBRT)
  7. Evidence of brain metastases
  8. NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure (defined as ≥ 160/100 mm Hg)
  9. Active infection or uncontrolled fever
  10. Clinically significant decrease in performance status (medical records) within 2 weeks of intended first dose administration
  11. Any other severe concomitant disease, disorder, or condition that could interfere with patient’s safety, ability to participate, or interpretation of study results
  12. Malignancies other than metastatic pancreatic adenocarcinoma within the last 3 years before study start, except for cervical carcinoma in situ, treated basal or squamous cell carcinoma
  13. Investigational therapy administered within 4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, whichever was longer, prior to the first scheduled day of dosing in this study
  14. Pregnant or breastfeeding subjects
  15. Known or suspected history of immunosuppression, including history of invasive opportunistic infections (e.g. tuberculosis [TB], histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, aspergillosis) despite infection resolution
  16. History of interstitial lung disease
  17. Stage C Child-Pugh liver cirrhosis
  18. Use of strong CYP3A4 inducers or inhibitors and/or strong UGT1A1 inhibitors within 14 days prior to Visit 1/Baseline visit
  19. Current use, or up to 14 days use prior to Visit1/Baseline visit, of an immunotherapy and live virus vaccines
  20. Participant must not have received colony stimulating factors (eg, granulocyte colony-stimulating factor, granulocyte macrophage colony stimulating factor, or recombinant erythropoietin) within 4 weeks prior initiating protocol therapy
  21. Participant has had any known Grade 3 or 4 anemia, neutropenia or thrombocytopenia due to prior chemotherapy that persisted > 4 weeks and was related to the most recent treatment
  22. Subjects that, in the investigator’s judgement, are likely to require whole brain irradiation, Whipple procedure, or distal and/or total pancreatectomy within 8 weeks from start of study

Location

  • Dallas, TX - Mary Crowley Cancer Research - Medical City
More Info: https://clinicaltrials.gov/ct2/show/NCT04825288

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Re: MC# 21-22