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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Pancreatic Cancer, Pleural Mesothelioma, 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, Prostate Cancer, Sarcoma, Tongue Cancer, Thymic Carcinoma, Urinary Tract Cancer

Intervention / Treatment
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* Drug: QBS10072S


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. 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.

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: Sequential Assignment
Interventional Model Description: The dose escalation scheme for this trial employs an mTPI-2 design.
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Peak Plasma Concentration (Cmax) | Determine the maximum plasma concentration of QBS10072S. | 28 days | 
| Area under the plasma concentration versus time curve (AUC) of QBS10072S | Determine the plasma concentration of QBS10072S over time. | 28 days | 
| 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 | 
| Time to maximum concentration of QBS10072S in plasma (Tmax) | Determine the time it takes to achieve maximum concentration of QBS10072S in plasma. | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Blurred vision, Loss of appetite, Speech difficulty, Changes in ability to think and learn, Changes in mood and personality, Persistent headaches, Neuropathologist, Magnetic resonance spectroscopy (MRS), Positron emission tomography (PET scan), Intraoperative MRI, Tumor removal, Craniotomy, Phase 1, Dose escalation, Metastatic, Brain metastasis, Brain metastases, GBM, Astrocytoma, Brain tumor, Cancer, Oncology, Glioblastoma, Glioblastoma multiforme, Brain, Neurology, Neuroscience, Headaches, Vomiting, Seizures, Drowsiness, Chemotherapy, Surgery, Radiation, Neuro-oncology, Standard external beam radiation therapy, Radiosurgery, Temozolomide, Bevacizumab, Avastin, Neurological exam, TMZ