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

Sponsor

Quadriga Biosciences, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04430842

Collaborator

Novotech (Australia) Pty Limited (Industry)

Enrollment

Locations

Arm

28.4

Anticipated Duration (Months)

Patients Per Site

0.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Astrocytoma Brain Cancer Brain Metastases Bladder Cancer Breast Cancer Cervical Cancer Cholangiocarcinoma Colorectal Cancer Esophagus Cancer Gastric Cancer Head and Neck Cancer Kidney Cancer Liver Cancer Lung Cancer Melanoma Ovarian Cancer Pancreatic Cancer Pleural Mesothelioma Prostate Cancer Sarcoma Tongue Cancer Thymic Carcinoma Urinary Tract Cancer	Drug: QBS10072S	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

Intervention Model Description:

The dose escalation scheme for this trial employs an mTPI-2 design.The dose escalation scheme for this trial employs an mTPI-2 design.

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jul 20, 2020

Anticipated Primary Completion Date :

Sep 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose escalation of QBS10072S Intravenous administration of QBS10072S once every 4 weeks starting at 3mg/m2 and increasing dose levels in subsequent cohorts.	Drug: QBS10072S QBS10072S targets cancers with high LAT1 expression.

Arm

Intervention/Treatment

Experimental: Dose escalation of QBS10072S

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

Drug: QBS10072S

QBS10072S targets cancers with high LAT1 expression.

Outcome Measures

Primary Outcome Measures

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

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.
Peak Plasma Concentration (Cmax) [28 days]
Determine the maximum plasma concentration of QBS10072S.
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or female participants aged ≥18 years at the time of informed consent.
Adequate Bone Marrow Function
Adequate renal function
Adequate Liver Function
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.
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

At least one measurable lesion (as defined by RECIST version 1.1) that has not been previously irradiated.
An ECOG PS 0 to 2.

Exclusion Criteria:

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.
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.
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).
Systemic anticancer therapy within 4 weeks prior to study entry
Bleeding esophageal or gastric varices <2 months prior to the date of informed consent.
Unmanageable ascites.
Baseline 12 lead ECG that demonstrates clinically relevant abnormalities that may affect patient safety or interpretation of study results
On therapeutic anticoagulation, except low molecular weight heparin, vitamin K antagonists or factor Xa inhibitors may be allowed following discussion with the Sponsor.
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).
Hypertension that cannot be controlled by medications (>150/90 mmHg despite optimal medical therapy) or requiring more than two medications for adequate control.