Dose Escalation Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of QBS10072S

Phase 1

Completed

• Conditions: Astrocytoma; Brain Metastases; Gastric Cancer; Kidney Cancer; Melanoma; Sarcoma; Bladder Cancer; Breast Cancer; Colorectal Cancer; Pancreatic Cancer
• Interventions: Drug: QBS10072S

• Registration Number: NCT04430842
• Lead Sponsor: Quadriga Biosciences, Inc.

Brief Summary

This is a multi-center, open-label, dose escalation study to determine the safety, tolerability, pharmacokinetics, pharmacodynamics, and maximum tolerated dose (MTD) of QBS10072S in patients with advanced or metastatic cancers with high LAT1 expression. The MTD of QBS10072S will be confirmed in patients with relapsed or refractory grade 4 astrocytoma.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-06-02
• Study First Submitted QC: 2020-06-10
• Study First Posted: 2020-06-12
• Study Start: 2020-07-20
• Primary Completion: 2022-09-21
• Study Completion: 2022-12-22
• Status Verified: 2023-01
• Last Update Submitted: 2023-01-16
• Last Update Posted: 2023-01-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

1. Male or female participants aged ≥18 years at the time of informed consent.

2. Adequate Bone Marrow Function

3. Adequate renal function

4. Adequate Liver Function

5. Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤1 except for AEs not constituting a safety risk by Investigator judgment.

6. A histological or cytological diagnosis of a solid tumor that is advanced/metastatic, patients intolerant to standard treatment or, resistant to standard therapy* (per NCCN guidelines) or for which no curative therapy is available for the following tumor types:

   • Bladder, Brain, Breast, Cervical, Cholangiocarcinoma, Colorectal, Esophageal, Gastric, Head and Neck, Kidney, Liver, Lung, Melanoma, Ovarian, Pancreatic, Pleural mesothelioma, Prostate, Sarcoma, Tongue cancer, Thymic carcinomas, Urinary tract

7. At least one measurable lesion (as defined by RECIST version 1.1) that has not been previously irradiated.

8. An ECOG PS 0 to 2.

Exclusion Criteria

1. Patients with tumor primarily localized to the brainstem or spinal cord. Presence of known active uncontrolled or symptomatic 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. Radiation therapy within 4 weeks prior to receiving the first QBS10072S dose (bone lesions requiring radiation may be treated with limited radiation therapy during this period).
6. Systemic anticancer therapy within 4 weeks prior to study entry
7. Bleeding esophageal or gastric varices <2 months prior to the date of informed consent.
8. Unmanageable ascites.
9. Baseline 12 lead ECG that demonstrates clinically relevant abnormalities that may affect patient safety or interpretation of study results
10. On therapeutic anticoagulation, except low molecular weight heparin, vitamin K antagonists or factor Xa inhibitors may be allowed following discussion with the Sponsor.
11. Any of the following in the previous 6 months: myocardial infarction, congenital long QT syndrome, Torsade de Pointes, clinically significant arrhythmias (including sustained ventricular tachyarrhythmia and ventricular fibrillation), left anterior hemiblock, bifascicular block, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (New York Heart Association class III or IV), cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary embolism or other clinical significant episode of thromboembolic disease. Ongoing cardiac dysrhythmias of NCI CTCAE Grade ≥2, atrial fibrillation of any grade (Grade ≥2 in the case of asymptomatic lone atrial fibrillation).
12. Hypertension that cannot be controlled by medications (>150/90 mmHg despite optimal medical therapy) or requiring more than two medications for adequate control.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Dose escalation of QBS10072S	QBS10072S	Intravenous administration of QBS10072S once every 4 weeks starting at 3mg/m2 and increasing dose levels in subsequent cohorts.

Primary Outcome Measures

Name	Time	Method
Determination of maximum tolerated dose (MTD)	28 days	MTD will be determined by presence of AEs as characterized by type, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study therapy.

Secondary Outcome Measures

Name	Time	Method
Peak Plasma Concentration (Cmax)	28 days	Determine the maximum plasma concentration of QBS10072S.
Safety and tolerability assessed by adverse events and serious adverse events	28 days	Safety and tolerability will be determined by adverse events as characterized by type, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study therapy.
Area under the plasma concentration versus time curve (AUC) of QBS10072S	28 days	Determine the plasma concentration of QBS10072S over time.
Half-life of QBS10072S in plasma (t1/2)	28 days	Determine the half life of QBS10072S in plasma; the half-life of a drug is the time taken for the plasma concentration of a drug to reduce to half its original value.
Time to maximum concentration of QBS10072S in plasma (Tmax)	28 days	Determine the time it takes to achieve maximum concentration of QBS10072S in plasma.

Trial Locations

Locations (2)

Sydney Southwest Private Hospital; 🇦🇺 Liverpool, New South Wales, Australia

St George Private Hospital; 🇦🇺 Kogarah, New South Wales, Australia