Back to resultsA Phase 1 Study to Evaluate Paclitaxel Conjugated CXC Receptor 4 Antagonist (MB1707) in Patients With Advanced Cancer
Primary Purpose
Advanced Solid Tumor, Breast Cancer, Non Small Cell Lung Cancer
Status
Not yet recruiting
Phase
Early Phase 1
Locations
Study Type
Interventional
Intervention
MB1707
Sponsored by
About this trial
This is an interventional treatment trial for Advanced Solid Tumor
Eligibility Criteria
Inclusion Criteria:
- Male or female participants aged ≥18 years at the time of informed consent.
- Patients who have previously received at least one line of standard systemic therapy for their advanced/metastatic cancer and have either progressed, recurred, or were intolerant to the previous treatment eligible for treatment with a paclitaxel-based regimen.
- Clinical Performance Status of Eastern Cooperative Oncology Group (ECOG) 0 or 1.
- Adequate bone marrow reserves
- Adequate major organ system function
- Female patients must not be pregnant or breastfeeding.
Exclusion Criteria:
- Patients with tumor primarily localized to the brainstem or spinal cord. Presence of known active uncontrolled or symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth.
- Patients with advanced/metastatic, symptomatic, visceral spread, that are at risk of life-threatening complications in the short term (including patients with massive uncontrolled effusions [pleural, pericardial, peritoneal], pulmonary lymphangitis, and over 50% liver involvement).
- Patients with any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ.
- Major surgery within 4 weeks prior to study entry.
- Systemic anticancer therapy within 4 weeks prior to study entry
- Bleeding esophageal or gastric varices <2 months prior to the date of informed consent.
- History of severe immediate hypersensitivity reaction to paclitaxel
- Active unstable or clinically significant medical condition
- History of any major cardiovascular conditions within the past 6 months
- Patients with known active, uncontrolled bacterial, fungal, or viral infection
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
MB1707 Single Dose Phase 1
Arm Description
Phase 1 MB1707 given as a single intravenous (IV) dose of 0.3 mg/kg
Outcomes
Primary Outcome Measures
Incidence of Adverse Events (AE) as characterized by type, frequency, severity (NCI CTCAE Version 5.0), timing, seriousness, and relationship to study therapy
Treatment-emergent AEs through 14 days after last protocol therapy will be summarized by Medical Dictionary for Regulatory Activities (MedDRA) Version 14.0 (or higher) System Organ Class and preferred term. The incidences and percentages of participants experiencing each AE preferred term will be summarized with descriptive statistics. AEs will also be summarized by NCI CTCAE, Version 5.0, by grade and by causality (attribution to study treatment).
Peak Plasma Concentration (Cmax)
Determine Maximum observed MB1707 concentration from the time of dosing (0 h) to the time of the last quantifiable MB1707 concentration following dose administration
Time to Cmax (Tmax)
Determine Time of maximum observed MB1707 concentrations (post-dose)
Area under the concentration-time curve from time 0 to the last quantifiable concentration (AUC0-t)
Determine Area under the MB1707 concentration-time curve from the time of dosing (0 h) to the time of the last quantifiable concentration following dose administration
Area under the concentration-time curve extrapolated to infinity (AUC∞)
Determine Area under the MB1707 concentration-time curve from the time of dosing (0 h), extrapolated to infinity
Half-life in plasma (t1/2)
Determine Apparent terminal phase half-life of MB1707
Total body clearance (CL)
Determine total body clearance MB1707
Volume of distribution (VZ)
Determine Volume of distribution based on the terminal Phase of MB1707
Secondary Outcome Measures
Full Information
NCT ID
NCT05465590
First Posted
July 16, 2022
Last Updated
July 18, 2022
Sponsor
Mainline Biosciences, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT05465590
Brief Title
A Phase 1 Study to Evaluate Paclitaxel Conjugated CXC Receptor 4 Antagonist (MB1707) in Patients With Advanced Cancer
Official Title
A Phase 1 Study to Evaluate the Pharmacokinetics and Safety of MB1707 in Patients With Advanced Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
December 2022 (Anticipated)
Primary Completion Date
November 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mainline Biosciences, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The study will evaluate the pharmacokinetics (PK) and safety of a single intravenous (IV) dose of 0.3 mg/kg MB1707 in patients with advanced cancers.
Detailed Description
MB1707, paclitaxel (PTX) conjugated CXC chemokine receptor 4 (CXCR4) peptide antagonist, a peptide-drug conjugate (PDC), for the treatment of cancer. MB1707 is a potent CXCR4 antagonist which inhibits tumor growth and metastasis by blocking the stromal cell derived factor 1 (SDF-1, a.k.a. CXCL12)/CXCR4 signaling pathway. MB1707 contains a conjugated drug, paclitaxel. By specific binding to CXCR4 overexpressed by the tumor cells, MB1707 has a built-in targeted delivery mechanism.
The study will evaluate the PK and safety of a single intravenous (IV) dose of 0.3 mg/kg MB1707 in patients with advanced cancers.
Up to 6 patients will be enrolled.
Patients will be treated with a single intravenous (IV) dose of MB1707 over 3 hours on Day 1 only.
Patients will be pre-medicated with an antihistamine (eg, diphenhydramine), a corticosteroid (e.g., dexamethasone), and a H2 receptor antagonist (e.g., famotidine), within 30 to 60 minutes prior to infusion at doses per institutional guidelines.
Patients will be observed for 60 minutes after Cycle 1 dose administration.
Patients will complete a 14-day Safety Follow-up Visit following the single dose.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Solid Tumor, Breast Cancer, Non Small Cell Lung Cancer, Ovary Cancer, Pancreatic Neoplasms
7. Study Design
Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Model Description
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
MB1707 Single Dose Phase 1
Arm Type
Experimental
Arm Description
Phase 1 MB1707 given as a single intravenous (IV) dose of 0.3 mg/kg
Intervention Type
Drug
Intervention Name(s)
MB1707
Intervention Description
MB1707 is a CXCR4 antagonist peptide-conjugated paclitaxel.
MB1707, paclitaxel (PTX) conjugated CXC chemokine receptor 4 (CXCR4) peptide antagonist, a peptide-drug conjugate (PDC), for the treatment of cancer. MB1707 is a potent CXCR4 antagonist which inhibits tumor growth and metastasis by blocking the stromal cell derived factor 1 (SDF-1, a.k.a. CXCL12)/CXCR4 signaling pathway. MB1707 contains a conjugated drug, paclitaxel. By specific binding to CXCR4 overexpressed by the tumor cells, MB1707 has a built-in targeted delivery mechanism.
Primary Outcome Measure Information:
Title
Incidence of Adverse Events (AE) as characterized by type, frequency, severity (NCI CTCAE Version 5.0), timing, seriousness, and relationship to study therapy
Description
Treatment-emergent AEs through 14 days after last protocol therapy will be summarized by Medical Dictionary for Regulatory Activities (MedDRA) Version 14.0 (or higher) System Organ Class and preferred term. The incidences and percentages of participants experiencing each AE preferred term will be summarized with descriptive statistics. AEs will also be summarized by NCI CTCAE, Version 5.0, by grade and by causality (attribution to study treatment).
Time Frame
14 days
Title
Peak Plasma Concentration (Cmax)
Description
Determine Maximum observed MB1707 concentration from the time of dosing (0 h) to the time of the last quantifiable MB1707 concentration following dose administration
Time Frame
2 days
Title
Time to Cmax (Tmax)
Description
Determine Time of maximum observed MB1707 concentrations (post-dose)
Time Frame
2 days
Title
Area under the concentration-time curve from time 0 to the last quantifiable concentration (AUC0-t)
Description
Determine Area under the MB1707 concentration-time curve from the time of dosing (0 h) to the time of the last quantifiable concentration following dose administration
Time Frame
2 days
Title
Area under the concentration-time curve extrapolated to infinity (AUC∞)
Description
Determine Area under the MB1707 concentration-time curve from the time of dosing (0 h), extrapolated to infinity
Time Frame
2 days
Title
Half-life in plasma (t1/2)
Description
Determine Apparent terminal phase half-life of MB1707
Time Frame
2 days
Title
Total body clearance (CL)
Description
Determine total body clearance MB1707
Time Frame
2 days
Title
Volume of distribution (VZ)
Description
Determine Volume of distribution based on the terminal Phase of MB1707
Time Frame
2 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female participants aged ≥18 years at the time of informed consent.
Patients who have previously received at least one line of standard systemic therapy for their advanced/metastatic cancer and have either progressed, recurred, or were intolerant to the previous treatment eligible for treatment with a paclitaxel-based regimen.
Clinical Performance Status of Eastern Cooperative Oncology Group (ECOG) 0 or 1.
Adequate bone marrow reserves
Adequate major organ system function
Female patients must not be pregnant or breastfeeding.
Exclusion Criteria:
Patients with tumor primarily localized to the brainstem or spinal cord. Presence of known active uncontrolled or symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth.
Patients with advanced/metastatic, symptomatic, visceral spread, that are at risk of life-threatening complications in the short term (including patients with massive uncontrolled effusions [pleural, pericardial, peritoneal], pulmonary lymphangitis, and over 50% liver involvement).
Patients with any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ.
Major surgery within 4 weeks prior to study entry.
Systemic anticancer therapy within 4 weeks prior to study entry
Bleeding esophageal or gastric varices <2 months prior to the date of informed consent.
History of severe immediate hypersensitivity reaction to paclitaxel
Active unstable or clinically significant medical condition
History of any major cardiovascular conditions within the past 6 months
Patients with known active, uncontrolled bacterial, fungal, or viral infection
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jaymes Holland
Phone
16502732627
Email
jaymes.holland@mainlinebiosciences.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Aaron Weitzman, MD
Organizational Affiliation
Mainline Biosciences
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Phase 1 Study to Evaluate Paclitaxel Conjugated CXC Receptor 4 Antagonist (MB1707) in Patients With Advanced Cancer
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