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

Breast Cancer Clinical Trial

Official title:

A Phase 1, Open Label, Multi-Center, Single and Multiple Dose, Dose Escalation and Expansion Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of QBS10072S in Previously Treated Patients With Advanced or Metastatic Cancers With High LAT1 Signatures, and in Patients With Relapsed or Refractory Grade 4 Astrocytoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04430842
• Other study ID #: QBS-72S-1001
• Status: Completed
• Phase: Phase 1
• Start date: July 20, 2020
• Est. completion date: December 22, 2022

Study information

• Verified date: January 2023
• Source: Quadriga Biosciences, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: December 22, 2022
• Est. primary completion date: September 21, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Astrocytoma
• Bladder Cancer
• Brain Cancer
• Brain Metastases
• Brain Neoplasms
• Breast Cancer
• Cervical Cancer
• Cholangiocarcinoma
• Colorectal Cancer
• Esophageal Neoplasms
• Esophagus Cancer
• Gastric Cancer
• Head and Neck Cancer
• Kidney Cancer
• Liver Cancer
• Lung Cancer
• Melanoma
• Mesothelioma
• Neoplasm Metastasis
• Ovarian Cancer
• Pancreatic Cancer
• Pleural Mesothelioma
• Prostate Cancer
• Sarcoma
• Thymic Carcinoma
• Thymoma
• Tongue Cancer
• Tongue Neoplasms
• Urinary Tract Cancer
• Urologic Neoplasms

Intervention

Drug:
• QBS10072S
QBS10072S targets cancers with high LAT1 expression.

Locations

Country	Name	City	State
Australia	St George Private Hospital	Kogarah	New South Wales
Australia	Sydney Southwest Private Hospital	Liverpool	New South Wales

Sponsors (2)

Lead Sponsor	Collaborator
Quadriga Biosciences, Inc.	Novotech (Australia) Pty Limited

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determination of maximum tolerated dose (MTD)	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.	28 days
Secondary	Safety and tolerability assessed by adverse events and serious adverse events	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.	28 days
Secondary	Peak Plasma Concentration (Cmax)	Determine the maximum plasma concentration of QBS10072S.	28 days
Secondary	Area under the plasma concentration versus time curve (AUC) of QBS10072S	Determine the plasma concentration of QBS10072S over time.	28 days
Secondary	Half-life of QBS10072S in plasma (t1/2)	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.	28 days
Secondary	Time to maximum concentration of QBS10072S in plasma (Tmax)	Determine the time it takes to achieve maximum concentration of QBS10072S in plasma.	28 days