Clinical trial NCT05465590: 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
Overall status: WITHDRAWN
Phase: EARLY_PHASE1
Conditions: Advanced Solid Tumor
Breast Cancer
Non Small Cell Lung Cancer
Ovary Cancer
Pancreatic Neoplasms
Lead sponsor: Mainline Biosciences, Inc.
Sponsor class: INDUSTRY
First posted: 2022-07-20
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single Group Assignment
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Male or female participants aged ≥18 years at the time of informed consent.
2. 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.
3. Clinical Performance Status of Eastern Cooperative Oncology Group (ECOG) 0 or 1.
4. Adequate bone marrow reserves
5. Adequate major organ system function
6. Female patients must not be pregnant or breastfeeding.

Exclusion Criteria:

1. 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.
2. 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).
3. 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.
4. Major surgery within 4 weeks prior to study entry.
5. Systemic anticancer therapy within 4 weeks prior to study entry
6. Bleeding esophageal or gastric varices \<2 months prior to the date of informed consent.
7. History of severe immediate hypersensitivity reaction to paclitaxel
8. Active unstable or clinically significant medical condition
9. History of any major cardiovascular conditions within the past 6 months
10. Patients with known active, uncontrolled bacterial, fungal, or viral infection

Primary outcomes:
measure: Incidence of Adverse Events (AE) as characterized by type, frequency, severity (NCI CTCAE Version 5.0), timing, seriousness, and relationship to study therapy
timeFrame: 14 days
measure: Peak Plasma Concentration (Cmax)
timeFrame: 2 days
measure: Time to Cmax (Tmax)
timeFrame: 2 days
measure: Area under the concentration-time curve from time 0 to the last quantifiable concentration (AUC0-t)
timeFrame: 2 days
measure: Area under the concentration-time curve extrapolated to infinity (AUC∞)
timeFrame: 2 days
measure: Half-life in plasma (t1/2)
timeFrame: 2 days
measure: Total body clearance (CL)
timeFrame: 2 days
measure: Volume of distribution (VZ)
timeFrame: 2 days
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Mainline Biosciences
name: Aaron Weitzman, MD
role: STUDY_DIRECTOR
References: