A Phase 1 Study to Evaluate Paclitaxel Conjugated CXC Receptor 4 Antagonist (MB1707) in Patients With Advanced Cancer

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase 1 Study to Evaluate the Pharmacokinetics and Safety of MB1707 in Patients With Advanced Cancer

Conditions
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Advanced Solid Tumor, Breast Cancer, Non Small Cell Lung Cancer, Ovary Cancer, Pancreatic Neoplasms

Intervention / Treatment
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* Drug: MB1707


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MB1707 Single Dose Phase 1<br>Phase 1 MB1707 given as a single intravenous (IV) dose of 0.3 mg/kg | Drug: MB1707<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | 14 days | 
| 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 | 2 days | 
| Time to Cmax (Tmax) | Determine Time of maximum observed MB1707 concentrations (post-dose) | 2 days | 
| 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 | 2 days | 
| 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 | 2 days | 
| Half-life in plasma (t1/2) | Determine Apparent terminal phase half-life of MB1707 | 2 days | 
| Total body clearance (CL) | Determine total body clearance MB1707 | 2 days | 
| Volume of distribution (VZ) | Determine Volume of distribution based on the terminal Phase of MB1707 | 2 days |