MC# 21-22 - A Phase I/II Randomized, Double-Blind, Placebo-Controlled Trial (1-Better) Examining Xb2001 (Anti-Il-1⍺ True Human Antibody) In Combination With Onivyde + 5-Fluorouracil + Leucovorin In Advanced Pancreatic Cancer
-
Agent(s): XB2001
-
Disease Type(s): Pancreatic
-
Phase(s): I, II
-
Drug Classification(s): Monoclonal Antibody, Targeted Therapy
-
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
- Written informed consent provided by the patient
- Age ≥18 years
- Histologically or cytologically confirmed pancreatic adenocarcinoma of exocrine pancreas that is metastatic, unresectable, or recurrent
- At least one measurable lesion according to Response Evaluation Criteria in Solid Tumor (RECIST v1.1)
- Documented disease progression after one prior gemcitabine-based therapy OR one FOLFIRINOX and gemcitabine combination therapy
- Eastern Cooperative Oncology Group (ECOG) performance of 0 or 1 or Karnofsky performance status (KPS) ≥ 70
- 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
- Full understanding of the study protocol procedures and willingness to comply with them
- Normal ECG or ECG without any clinically significant findings with QTc < 470 ms
- For women of childbearing potential (WOCBP), a negative serum pregnancy test result at Screening
- 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.
- 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.
- At least 14 days since the last cancer treatment including: chemotherapy, radiation therapy, surgery, hormonal therapy prior to baseline visit
Exclusion Criteria
- History of treatment with XB2001 for any reason
- Clinically significant GI disorders
- Severe arterial thromboembolic events less than 6 months before inclusion
- Severe hypersensitivity to 5-FU
- Use of warfarin within 4 weeks of screening or any time during the study
- Prior Whole Brain Radiation Therapy (WBRT)
- Evidence of brain metastases
- NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure (defined as ≥ 160/100 mm Hg)
- Active infection or uncontrolled fever
- Clinically significant decrease in performance status (medical records) within 2 weeks of intended first dose administration
- Any other severe concomitant disease, disorder, or condition that could interfere with patient’s safety, ability to participate, or interpretation of study results
- 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
- 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
- Pregnant or breastfeeding subjects
- Known or suspected history of immunosuppression, including history of invasive opportunistic infections (e.g. tuberculosis [TB], histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, aspergillosis) despite infection resolution
- History of interstitial lung disease
- Stage C Child-Pugh liver cirrhosis
- Use of strong CYP3A4 inducers or inhibitors and/or strong UGT1A1 inhibitors within 14 days prior to Visit 1/Baseline visit
- Current use, or up to 14 days use prior to Visit1/Baseline visit, of an immunotherapy and live virus vaccines
- 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
- 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
- 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
