A Phase I, Dose Escalation Study of BNC101 (Anti-LGR5 Humanized Monoclonal Antibody) in Patients With Metastatic Colorectal Cancer.
Overview
- Phase
- Phase 1
- Intervention
- BNC101 Solution for Infusion
- Conditions
- Colorectal Cancer
- Sponsor
- Bionomics Limited
- Enrollment
- 22
- Locations
- 4
- Primary Endpoint
- Maximum Tolerated Dose
- Status
- Terminated
- Last Updated
- 7 years ago
Overview
Brief Summary
The purpose of this study is to determine the maximum tolerated dose (which will be the dose recommended for a Phase 2 study), safety, tolerability and pharmacokinetic profile (study of movement of the drug within the body, including absorption and distribution) of the study drug, BNC101 when administered intravenously as a single agent or in combination with chemotherapy in patients with metastatic colorectal cancer who have failed at least 1 or 2 lines of chemotherapy.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Signed written Informed Consent
- •Age \> 18 years
- •Eastern Cooperative Oncology Group (ECOG) score 0 -
- •Histologically or cytologically confirmed colorectal cancer patients who have failed at least 2 lines of chemotherapy (monotherapy treatment cohorts) or at least 1 line of chemotherapy (combination treatment cohorts) for metastatic disease, and in the opinion of both physician and patient it is not unreasonable to try experimental therapy. Adjuvant FOLFOX within the last 6 months is considered a line of therapy. A maintenance strategy post 1st line treatment is not considered as an additional line of therapy.
- •Patients must have accessible tumor lesions amenable to biopsy which would not put the patient or their treatment at risk. Patients in monotherapy escalation cohort 3 and onwards, the monotherapy expansion cohort, and all combination treatment patients, agree and are willing to provide 2 serial tumor lesion biopsies (a minimum of 2 fresh cores/punches preferred whenever possible). Biopsies can be from liver metastases, in lieu of the primary tumor. The presence of tumor tissue in fresh biopsies is to be certified by a trained pathologist using appropriate extemporaneous histology or cytology procedures. Refer to Appendix 6 for biopsy procedures.
- •All AEs of any prior chemotherapy, surgery, or radiotherapy, must have resolved to Grade ≤
- •Measurable or evaluable disease per RECIST version 1.
- •No known brain metastases (see also exclusion criterion No. 10).
- •Life expectancy of at least \> 12 weeks.
- •Normal organ and marrow function:
Exclusion Criteria
- •Inability to comply with study and follow-up procedures (including, but not limited to: geographical or administrative reasons, and planned vacation absences for more than 7 consecutive days during the study).
- •Women who are pregnant or lactating.
- •Colorectal cancer patients going on to receive 1st line therapy for metastatic disease.
- •Treatment with chemotherapy, immunotherapy, biologic therapy, or radiation therapy as cancer therapy within 4 weeks before initiation of study treatment. Six weeks should have elapsed if prior chemotherapy treatment included nitrosoureas or mitomycin C.
- •Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to Day 1 of Cycle
- •Patients who have received antibody-based therapies within 28 days or 5 half-lives of the agent, whichever is longer.
- •Major surgery, other than diagnostic surgery, within 6 weeks before first study drug administration.
- •Clinically detectable (by physical exam) third-space fluid collections (e.g., ascites or pleural effusion) that cannot be controlled by drainage or other procedures prior to study entry.
- •Any uncontrolled medical or psychiatric risk factors which would contraindicate the use or impair the ability of the patient to provide informed consent, receive protocol therapy or may impose excessive risk to the patient.
- •Central nervous system (CNS) metastases, unless previously treated and well-controlled for at least 3 months (defined as clinically stable, no edema, no steroids and stable in 2 scans at least 4 weeks apart). Patients who display signs or symptoms of CNS metastases or should be imaged with CT or magnetic resonance imaging (MRI) of the head. Should metastases, including meningeal deposits be detected, these patients will not be treated with BNC
Arms & Interventions
Group/Stream 1 - Monotherapy
Patient group: Patients who have failed at least two lines of chemotherapy for metastatic disease. Treatment: BNC101 administered via intravenous infusion over 60 minutes weekly. Patients with stable disease or a response at or after day 56 (2 cycles) will be allowed to continue to receive weekly doses of BNC101 until disease progression.
Intervention: BNC101 Solution for Infusion
Group/Stream 2 - Combination Chemo
Patient Group: Patients who have failed at least one line of chemotherapy for metastatic disease. Treatment: BNC101 administered in combination with FOLFIRI Participants will be treated until disease progression, intolerable toxicity, withdrawal of consent, or study termination by the Sponsor, whichever occurs first.
Intervention: BNC101 in combination with FOLFIRI
Outcomes
Primary Outcomes
Maximum Tolerated Dose
Time Frame: DLT period of 28 days per dose level
To determine the maximum tolerated dose (MTD) of BNC101, both as single agent and in combination chemotherapy in metastatic colorectal cancer patients.