The purpose of this Phase I, Multi-Center, Open-Label Study is to evaluate the safety, tolerability, Pharmacokinetics, Pharmacodynamics and anti-tumor activity of KF-0210 in participants with advanced solid tumors. The study will be conducted in two parts: phase Ia, and phase Ib.
Phase 1a: The primary objective of the phase 1a part of the study is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamic and anti-tumor activity of oral KF-0210 as a single agent in participants with advanced solid tumors, to identify the dose-limiting toxicity and establish the maximum tolerated dose, or maximum administered dose and/or the recommended Phase II dose of KF-0210 in participants with advanced solid tumors. Phase 1b: The primary objective of the phase 1b part of the study is to assess the safety, pharmacokinetics, pharmacodynamic and anti-tumor activity of KF-0210 in combination with Atezolizumab in patients with colorectal cancer (CRC) (MSS), lung cancer (LC), squamous cell carcinoma of the esophagus (SCCE), gastric cancer (GC), and bladder cancer (BC).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
14
KF-0210 tablet will be orally administered as a single agent at 120 mg once daily (QD) continuously, until the disease progression, intolerance, or informed consent withdrawal.
KF-0210 tablet will be orally administered as a single agent at 240 mg once daily (QD) continuously, until the disease progression, intolerance, or informed consent withdrawal.
KF-0210 tablet will be orally administered as a single agent at 450 mg once daily (QD) continuously, until the disease progression, intolerance, or informed consent withdrawal.
Scientia Clinical Research Limited
Randwick, New South Wales, Australia
Percentage of patient with adverse events / serious adverse events (AEs/SAEs) [Safety and Tolerability]
Adverse events will be assessed according to CTCAE V5.0, and be coded according to the MedDRA Dictionary
Time frame: From consent through 28 days (±7 days) after the last dose or before starting other anti-tumor treatment (whichever occurs earlier)(up to approximately 1 year))
Dose limiting toxicity (DLT) of KF-0210 [Tolerability]
Dose limiting toxicity (DLT) will be considered to be related to KF-0210 according to CTCAE V5.0 including hematology toxicities, non-hematological toxicities and any other toxicities.
Time frame: From Cycle 1 Day 1 to Cycle 1 Day 21, each cycle is 21 days.
Maximum tolerated dose (MTD) of KF-0210 alone [Tolerability]
The Maximum tolerated dose (MTD) is defined as the highest dose at which ≤1、6 participants occurred dose limiting toxicity at each dose level.
Time frame: Up to 21 days after first administration in cycle 1, each cycle is 21 days
Change of Body Weight from Baseline [Safety]
Body Weight measured in kilogram (kg)
Time frame: On date of screening (within 7 days before the first dose), Day 1 of each cycle (each cycle is 21 days), and at the end of treatment/withdrawal (up to approximately 1 year)
Change of Body Temperature from Baseline [Safety]
Axillary temperature measured in celsius
Time frame: From screening to the end of treatment/withdrawal (up to approximately 1 year)
Change of Pulse rate from Baseline [Safety]
Pulse rate measured per minute
Time frame: From screening to the end of treatment/withdrawal (up to approximately 1 year)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
KF-0210 tablet will be orally administered as a single agent at 600 mg once daily (QD) continuously, until the disease progression, intolerance, or informed consent withdrawal.
KF-0210 tablet will be orally administered at dosage RP2D-2 once daily (QD) in combination with Atezolizumab that will be administered at 1200 mg every 3 weeks via intravenously infusion.
KF-0210 tablet will be orally administered at dosage RP2D-1 once daily (QD) in combination with Atezolizumab that will be administered at 1200 mg every 3 weeks via intravenously infusion.
KF-0210 tablet will be orally administered at dosage RP2D once daily (QD) in combination with Atezolizumab that will be administered at 1200 mg every 3 weeks via intravenously infusion.
Change of Systolic pressure from Baseline [Safety]
Blood pressure measured in mmHg
Time frame: From screening to the end of treatment/withdrawal (up to approximately 1 year)
Change of Diastolic pressure from Baseline [Safety]
Blood pressure measured in mmHg
Time frame: From screening to the end of treatment/withdrawal (up to approximately 1 year)
Change of Heart rate from Baseline [Safety]
Heart rate in beats per minute (Bpm) through 12-lead ECG assessment
Time frame: From screening to the end of treatment/withdrawal (up to approximately 1 year)
Change of R-R interval from Baseline [Safety]
R-R interval measured in millisecond through 12-lead ECG assessment
Time frame: From screening to the end of treatment/withdrawal (up to approximately 1 year)
Change of P-R interval from Baseline [Safety]
P-R interval measured in millisecond through 12-lead ECG assessment
Time frame: From screening to the end of treatment/withdrawal (up to approximately 1 year)
Change of QRS complex from Baseline [Safety]
QRS complex measured in millisecond through 12-lead ECG assessment
Time frame: From screening to the end of treatment/withdrawal (up to approximately 1 year)
Chang of QT interval from Baseline [Safety]
QT interval measured in millisecond through 12-lead ECG assessment
Time frame: From screening to the end of treatment/withdrawal (up to approximately 1 year)
Change of corrected QT (QTc) interval from Baseline [Safety]
corrected QT (QTc) interval measured in millisecond through 12-lead ECG assessment
Time frame: From screening to the end of treatment/withdrawal (up to approximately 1 year)
Change of Fridericia's Correction QT (QTcF) interval from Baseline [Safety]
Fridericia's Correction QT (QTcF) interval measured in millisecond through 12-lead ECG assessment.
Time frame: From screening to the end of treatment/withdrawal (up to approximately 1 year)
Change of Eastern Cooperative Oncology Group-Performance Status (ECOG PS) from Baseline [Safety]
The performance status will be evaluated in accordance with the Eastern Cooperative Oncology Group (ECOG) criteria with the score range in 0 to 5. A score of 0 represents fully normal activity and a score of 5 represents death.
Time frame: On date of screening (within 7 days before the first dose), Day 1 of each cycle (each cycle is 21 days), and at the end of treatment/withdrawal (up to approximately 1 year)
Change of Total Protein (TP) from Baseline [Safety]
Total Protein (TP) measured in g/dL
Time frame: On date of screening (within 7 days before the first dose), Day 8, Day15, Day 21 of cycle 1 (each cycle is 21 days), Day 1 of each cycle from the cycle 2, and at the end of treatment/withdrawal (up to approximately 1 year)
Change of Albumin (ALB) from Baseline [Safety]
Albumin(ALB) measured in g/dL
Time frame: On date of screening (within 7 days before the first dose), Day 8, Day15, Day 21 of cycle 1 (each cycle is 21 days), Day 1 of each cycle from the cycle 2, and at the end of treatment/withdrawal (up to approximately 1 year)
Change of Alanine aminotransferase (ALT) from Baseline [Safety]
Alanine aminotransferase (ALT) measured in IU/L
Time frame: On date of screening (within 7 days before the first dose), Day 8, Day15, Day 21 of cycle 1 (each cycle is 21 days), Day 1 of each cycle from the cycle 2, and at the end of treatment/withdrawal (up to approximately 1 year)
Change of Aspartate aminotransferase (AST) from Baseline [Safety]
Aspartate aminotransferase (AST) measured in IU/L
Time frame: On date of screening (within 7 days before the first dose), Day 8, Day15, Day 21 of cycle 1 (each cycle is 21 days), Day 1 of each cycle from the cycle 2, and at the end of treatment/withdrawal (up to approximately 1 year)
Change of Alkaline phosphatase (ALP/AKP) from Baseline [Safety]
Alkaline phosphatase (ALP/AKP) measured in IU/L
Time frame: On date of screening (within 7 days before the first dose), Day 8, Day15, Day 21 of cycle 1 (each cycle is 21 days), Day 1 of each cycle from the cycle 2, and at the end of treatment/withdrawal (up to approximately 1 year)
Change of Total bilirubin from Baseline [Safety]
Total bilirubin measured in mg/dL
Time frame: On date of screening (within 7 days before the first dose), Day 8, Day15, Day 21 of cycle 1 (each cycle is 21 days), Day 1 of each cycle from the cycle 2, and at the end of treatment/withdrawal (up to approximately 1 year)
Change of Direct bilirubin from Baseline [Safety]
Direct bilirubin measured in mg/dL
Time frame: On date of screening (within 7 days before the first dose), Day 8, Day15, Day 21 of cycle 1 (each cycle is 21 days), Day 1 of each cycle from the cycle 2, and at the end of treatment/withdrawal (up to approximately 1 year)
Change of Indirect bilirubin from Baseline [Safety]
Indirect bilirubin measured in mg/dL
Time frame: On date of screening (within 7 days before the first dose), Day 8, Day15, Day 21 of cycle 1 (each cycle is 21 days), Day 1 of each cycle from the cycle 2, and at the end of treatment/withdrawal (up to approximately 1 year)
Change of Glutamyl transpeptidase from Baseline [Safety]
Glutamyl transpeptidase measured in U/L
Time frame: On date of screening (within 7 days before the first dose), Day 8, Day15, Day 21 of cycle 1 (each cycle is 21 days), Day 1 of each cycle from the cycle 2, and at the end of treatment/withdrawal (up to approximately 1 year)
Change of Blood glucose from Baseline [Safety]
Blood glucose measured in mg/dL
Time frame: On date of screening (within 7 days before the first dose), Day 8, Day15, Day 21 of cycle 1 (each cycle is 21 days), Day 1 of each cycle from the cycle 2, and at the end of treatment/withdrawal (up to approximately 1 year)
Change of Urea from Baseline [Safety]
Urea measured in mg/dL
Time frame: On date of screening (within 7 days before the first dose), Day 8, Day15, Day 21 of cycle 1 (each cycle is 21 days), Day 1 of each cycle from the cycle 2, and at the end of treatment/withdrawal (up to approximately 1 year)
Change of Uric acid from Baseline [Safety]
Uric acid measured in mg/dL
Time frame: On date of screening (within 7 days before the first dose), Day 8, Day15, Day 21 of cycle 1 (each cycle is 21 days), Day 1 of each cycle from the cycle 2, and at the end of treatment/withdrawal (up to approximately 1 year)
Change of Creatinine from Baseline [Safety]
Creatinine measured in mg/dL
Time frame: On date of screening (within 7 days before the first dose), Day 8, Day15, Day 21 of cycle 1 (each cycle is 21 days), Day 1 of each cycle from the cycle 2, and at the end of treatment/withdrawal (up to approximately 1 year)
Change of Creatinine Kinase from Baseline [Safety]
Creatinine Kinase measured in IU/L
Time frame: On date of screening (within 7 days before the first dose), Day 8, Day15, Day 21 of cycle 1 (each cycle is 21 days), Day 1 of each cycle from the cycle 2, and at the end of treatment/withdrawal (up to approximately 1 year)
Change of Total Cholesterol from Baseline [Safety]
Total Cholesterol measured in mmol/L
Time frame: On date of screening (within 7 days before the first dose), Day 8, Day15, Day 21 of cycle 1 (each cycle is 21 days), Day 1 of each cycle from the cycle 2, and at the end of treatment/withdrawal (up to approximately 1 year)
Change of Triglycerides from Baseline [Safety]
Triglycerides measured in mmol/L
Time frame: On date of screening (within 7 days before the first dose), Day 8, Day15, Day 21 of cycle 1 (each cycle is 21 days), Day 1 of each cycle from the cycle 2, and at the end of treatment/withdrawal (up to approximately 1 year)
Change of Potassium, Sodium, Chloride or Calcium from Baseline [Safety]
Potassium, Sodium, Chloride or Calcium measured in mmol/dL
Time frame: On date of screening (within 7 days before the first dose), Day 8, Day15, Day 21 of cycle 1 (each cycle is 21 days), Day 1 of each cycle from the cycle 2, and at the end of treatment/withdrawal (up to approximately 1 year)
Change of Leukocyte Count from Baseline [Safety]
Leukocyte Count measured in K/uL
Time frame: On date of screening (within 7 days before the first dose), Day 8, Day15, Day 21 of cycle 1 (each cycle is 21 days), Day 1 of each cycle from the cycle 2, and at the end of treatment/withdrawal (up to approximately 1 year)
Change of Neutrophil Count from Baseline [Safety]
Neutrophil Count in K/uL
Time frame: On date of screening (within 7 days before the first dose), Day 8, Day15, Day 21 of cycle 1 (each cycle is 21 days), Day 1 of each cycle from the cycle 2, and at the end of treatment/withdrawal (up to approximately 1 year)
Change of Percentage of Neutrophil from Baseline [Safety]
Percentage of Neutrophil will be measured
Time frame: On date of screening (within 7 days before the first dose), Day 8, Day15, Day 21 of cycle 1 (each cycle is 21 days), Day 1 of each cycle from the cycle 2, and at the end of treatment/withdrawal (up to approximately 1 year)
Change of Lymphocyte Count from Baseline [Safety]
Lymphocyte Count measured in K/uL
Time frame: On date of screening (within 7 days before the first dose), Day 8, Day15, Day 21 of cycle 1 (each cycle is 21 days), Day 1 of each cycle from the cycle 2, and at the end of treatment/withdrawal (up to approximately 1 year)
Change of Percentage of Lymphocyte from Baseline [Safety]
Percentage of Lymphocyte will be measured
Time frame: On date of screening (within 7 days before the first dose), Day 8, Day15, Day 21 of cycle 1 (each cycle is 21 days), Day 1 of each cycle from the cycle 2, and at the end of treatment/withdrawal (up to approximately 1 year)
Change of Monocytes Count from Baseline [Safety]
Monocytes Count measured in K/uL
Time frame: On date of screening (within 7 days before the first dose), Day 8, Day15, Day 21 of cycle 1 (each cycle is 21 days), Day 1 of each cycle from the cycle 2, and at the end of treatment/withdrawal (up to approximately 1 year)
Change of Percentage of Monocytes from Baseline [Safety]
Percentage of Monocytes will be measured
Time frame: On date of screening (within 7 days before the first dose), Day 8, Day15, Day 21 of cycle 1 (each cycle is 21 days), Day 1 of each cycle from the cycle 2, and at the end of treatment/withdrawal (up to approximately 1 year)
Change of Eosinophils Count from Baseline [Safety]
Eosinophils Count measured in K/uL
Time frame: On date of screening (within 7 days before the first dose), Day 8, Day15, Day 21 of cycle 1 (each cycle is 21 days), Day 1 of each cycle from the cycle 2, and at the end of treatment/withdrawal (up to approximately 1 year)
Change of Percentage of Eosinophils from Baseline [Safety]
Percentage of Eosinophils will be measured
Time frame: On date of screening (within 7 days before the first dose), Day 8, Day15, Day 21 of cycle 1 (each cycle is 21 days), Day 1 of each cycle from the cycle 2, and at the end of treatment/withdrawal (up to approximately 1 year)
Change of Basophil Count from Baseline [Safety]
Basophil Count measured in K/uL
Time frame: On date of screening (within 7 days before the first dose), Day 8, Day15, Day 21 of cycle 1 (each cycle is 21 days), Day 1 of each cycle from the cycle 2, and at the end of treatment/withdrawal (up to approximately 1 year)
Change of Percentage of Basophil from Baseline [Safety]
Percentage of Basophil will be measured
Time frame: On date of screening (within 7 days before the first dose), Day 8, Day15, Day 21 of cycle 1 (each cycle is 21 days), Day 1 of each cycle from the cycle 2, and at the end of treatment/withdrawal (up to approximately 1 year)
Change of Erythrocyte Count from Baseline [Safety]
Erythrocyte Count measured in K/uL
Time frame: On date of screening (within 7 days before the first dose), Day 8, Day15, Day 21 of cycle 1 (each cycle is 21 days), Day 1 of each cycle from the cycle 2, and at the end of treatment/withdrawal (up to approximately 1 year)
Change of Hemoglobin from Baseline [Safety]
Hemoglobin measured in mg/dL
Time frame: On date of screening (within 7 days before the first dose), Day 8, Day15, Day 21 of cycle 1 (each cycle is 21 days), Day 1 of each cycle from the cycle 2, and at the end of treatment/withdrawal (up to approximately 1 year)
Change of Hematocrit Platelets from Baseline [Safety]
Hematocrit Platelets measured in K/uL
Time frame: On date of screening (within 7 days before the first dose), Day 8, Day15, Day 21 of cycle 1 (each cycle is 21 days), Day 1 of each cycle from the cycle 2, and at the end of treatment/withdrawal (up to approximately 1 year)
Change of Coagulation test-Activated partial thromboplastin time (APTT) from Baseline [Safety]
Activated partial thromboplastin time (APTT) measured in seconds
Time frame: On date of screening (within 7 days before the first dose), Day 8, Day15, Day 21 of cycle 1 (each cycle is 21 days), Day 1 of each cycle from the cycle 2, and at the end of treatment/withdrawal (up to approximately 1 year)
Change of Coagulation test-Prothrombin time (PT) from Baseline [Safety]
Prothrombin time (PT) measured in seconds
Time frame: On date of screening (within 7 days before the first dose), Day 8, Day15, Day 21 of cycle 1 (each cycle is 21 days), Day 1 of each cycle from the cycle 2, and at the end of treatment/withdrawal (up to approximately 1 year)
Change of Coagulation test-Fibrinogen(FIB) from Baseline [Safety]
Fibrinogen(FIB) measured in mmol/L
Time frame: On date of screening (within 7 days before the first dose), Day 8, Day15, Day 21 of cycle 1 (each cycle is 21 days), Day 1 of each cycle from the cycle 2, and at the end of treatment/withdrawal (up to approximately 1 year)
Change of Coagulation test-Thrombin time (TT) from Baseline [Safety]
Thrombin time (TT) measured in seconds
Time frame: On date of screening (within 7 days before the first dose), Day 8, Day15, Day 21 of cycle 1 (each cycle is 21 days), Day 1 of each cycle from the cycle 2, and at the end of treatment/withdrawal (up to approximately 1 year)
Change of Urine pH from Baseline [Safety]
pH value will be measured
Time frame: On date of screening (within 7 days before the first dose), Day 8, Day15, Day 21 of cycle 1 (each cycle is 21 days), Day 1 of each cycle from the cycle 2, and at the end of treatment/withdrawal (up to approximately 1 year)
Change of Specific gravity of urine from Baseline [Safety]
Specific gravity value will be measured
Time frame: On date of screening (within 7 days before the first dose), Day 8, Day15, Day 21 of cycle 1 (each cycle is 21 days), Day 1 of each cycle from the cycle 2, and at the end of treatment/withdrawal (up to approximately 1 year)
Change in Occult blood result from Baseline [Safety]
The result will be recorded as either positive or negative
Time frame: On date of screening (within 7 days before the first dose), Day 8, Day15, Day 21 of cycle 1 (each cycle is 21 days), Day 1 of each cycle from the cycle 2, and at the end of treatment/withdrawal (up to approximately 1 year)
Change in Urine Bilirubin result from Baseline [Safety]
Urine bilirubin will be measure in µmol/L
Time frame: On date of screening (within 7 days before the first dose), Day 8, Day15, Day 21 of cycle 1 (each cycle is 21 days), Day 1 of each cycle from the cycle 2, and at the end of treatment/withdrawal (up to approximately 1 year)
Change in Urine protein from Baseline [Safety]
Urine protein will be measured in mg/dL
Time frame: On date of screening (within 7 days before the first dose), Day 8, Day15, Day 21 of cycle 1 (each cycle is 21 days), Day 1 of each cycle from the cycle 2, and at the end of treatment/withdrawal (up to approximately 1 year)
Change in Urine Glucose from Baseline [Safety]
Urine Glucose will be measured in mg/dL
Time frame: On date of screening (within 7 days before the first dose), Day 8, Day15, Day 21 of cycle 1 (each cycle is 21 days), Day 1 of each cycle from the cycle 2, and at the end of treatment/withdrawal (up to approximately 1 year)
Change in Ketones from Baseline [Safety]
Ketones will be measured in mg/dL
Time frame: On date of screening (within 7 days before the first dose), Day 8, Day15, Day 21 of cycle 1 (each cycle is 21 days), Day 1 of each cycle from the cycle 2, and at the end of treatment/withdrawal (up to approximately 1 year)
Change in Urobilinogen from Baseline [Safety]
Urobilinogen will be measured in EU/dL
Time frame: On date of screening (within 7 days before the first dose), Day 8, Day15, Day 21 of cycle 1 (each cycle is 21 days), Day 1 of each cycle from the cycle 2, and at the end of treatment/withdrawal (up to approximately 1 year)
Change in Urinary leukocyte from Baseline [Safety]
Urinary leukocyte will be counted in K/uL
Time frame: On date of screening (within 7 days before the first dose), Day 8, Day15, Day 21 of cycle 1 (each cycle is 21 days), Day 1 of each cycle from the cycle 2, and at the end of treatment/withdrawal (up to approximately 1 year)
Change in Urine erythrocytes from Baseline [Safety]
Urine erythrocytes will be counted in K/uL
Time frame: On date of screening (within 7 days before the first dose), Day 8, Day15, Day 21 of cycle 1 (each cycle is 21 days), Day 1 of each cycle from the cycle 2, and at the end of treatment/withdrawal (up to approximately 1 year)
Change in Urine Nitrites from Baseline [Safety]
Urobilinogen will be measured in mg/dL
Time frame: On date of screening (within 7 days before the first dose), Day 8, Day15, Day 21 of cycle 1 (each cycle is 21 days), Day 1 of each cycle from the cycle 2, and at the end of treatment/withdrawal (up to approximately 1 year)
Clinically significant abnormality in physical examinations
Physical examination includes skin, head, eyes, ears, nose and throat, lymph nodes, heart, chest, abdomen and extremities, and nervous system (speech, cranial nerves, motor ability, tendon reflexes, sensations, free movement)
Time frame: On date of screening (within 7 days before the first dose), Day 1 of each cycle (each cycle is 21 days), and at the end of treatment/withdrawal (up to approximately 1 year)
Maximum observed plasma concentration (Cmax)
For KF-0210 alone in phase Ia, and for KF-0210 and Atezolizumab in Phase Ib. Calculated by non-compartmental analysis (NCA) for WinNonlin V8.2 (or above).
Time frame: Phase I a: specific time points from Cycle 1 Day 1 to Cycle 1 Day 8; Phase 1b: specific time points from Cycle 1 Day 1 to Cycle 4 Day 5, each cycle is 21 days.
Time of maximum plasma concentration (Tmax)
For KF-0210 alone in phase Ia, and for KF-0210 and Atezolizumab in Phase Ib. Calculated by non-compartmental analysis (NCA) for WinNonlin V8.2 (or above).
Time frame: Phase I a: specific time points from Cycle 1 Day 1 to Cycle 1 Day 8; Phase 1b: specific time points from Cycle 1 Day 1 to Cycle 4 Day 15. Each cycle is 21 days.
Area under the plasma concentration-time curve from time-zero extrapolated to infinite time (AUC0-inf)
For KF-0210 alone in phase Ia, and for KF-0210 and Atezolizumab in Phase Ib. Calculated by non-compartmental analysis (NCA) for WinNonlin V8.2 (or above).
Time frame: Phase I a: specific time points from Cycle 1 Day 1 to Cycle 1 Day 8; Phase 1b: specific time points from Cycle 1 Day 1 to Cycle 4 Day 15. Each cycle is 21 days.
Area under the plasma concentration-time curve from time-zero to the time of the last measurable concentration (AUC0-t) of KF-0210
For KF-0210 alone in phase Ia, and for KF-0210 and Atezolizumab in Phase Ib. Calculated by non-compartmental analysis (NCA) for WinNonlin V8.2 (or above).
Time frame: Phase I a: specific time points from Cycle 1 Day 1 to Cycle 1 Day 8; Phase 1b: specific time points from Cycle 1 Day 1 to Cycle 4 Day 15. Each cycle is 21 days.
Terminal half-life (T1/2) of KF-0210
For KF-0210 alone in phase Ia, and for KF-0210 and Atezolizumab in Phase Ib. Calculated by non-compartmental analysis (NCA) for WinNonlin V8.2 (or above).
Time frame: Phase I a: specific time points from Cycle 1 Day 1 to Cycle 1 Day 8; Phase 1b: specific time points from Cycle 1 Day 1 to Cycle 4 Day 15. Each cycle is 21 days.
Accumulation ratio (Rac)
For KF-0210 alone in phase Ia, and for KF-0210 and Atezolizumab in Phase Ib. Calculated by non-compartmental analysis (NCA) for WinNonlin V8.2 (or above).
Time frame: Phase I a: specific time points from Cycle 1 Day 1 to Cycle 1 Day 8; Phase 1b: specific time points from Cycle 1 Day 1 to Cycle 4 Day 15. Each cycle is 21 days.
Cmin to Cmax fluctuation between dose time and Tau (DF)
For KF-0210 alone in phase Ia, and for KF-0210 and Atezolizumab in Phase Ib. Calculated by non-compartmental analysis (NCA) for WinNonlin V8.2 (or above).
Time frame: Phase I a: specific time points from Cycle 1 Day 1 to Cycle 1 Day 8; Phase 1b: specific time points from Cycle 1 Day 1 to Cycle 4 Day 15. Each cycle is 21 days.
Blood cytokines/chemokines levels
Biomarker for pharmacodynamic assessment including interferon (IFN-γ), tumor necrosis factor (TNF-α), CXCL10 and CCL5.
Time frame: Up to 21 days after first administration in cycle 1, each cycle is 21 days.
Urine prostaglandin metabolites level
To explore the prostaglandin metabolites in urine
Time frame: Up to 21 days after first administration in cycle 1, each cycle is 21 days.
Tumor T cell infiltration
Tumor biopsies will be analyzed by immunohistochemistry (IHC) for CD3+ T cells, CD8+ T cells and PD-L1 expression.
Time frame: Up to 21 days after first administration in cycle 1, each cycle is 21 days.
Change in tumor size from baseline
Tumor assessment with CT scan or MRI. The anti-tumor activity will be evaluated according to the RECIST V1.1.
Time frame: From screening through the last dose of treatment, each cycle is 21 days.
Objective response rate (ORR)
Tumor assessment with CT scan or MRI. The tumor lesions will be evaluated according to the RECIST V1.1 standard, and categorized into complete response(CR), partial response (PR), stable disease (SD) , and progressive disease (PD).
Time frame: From screening through the last dose of treatment, each cycle is 21 days.
Duration of response (DOR) (days)
Tumor assessment with CT scan or MRI. The tumor lesions will be evaluated according to the RECIST V1.1 standard, and categorized into complete response(CR), partial response (PR), stable disease (SD) , and progressive disease (PD).
Time frame: From screening through the last dose of treatment, each cycle is 21 days.
Disease control rate (DCR)
Tumor assessment with CT scan or MRI. The tumor lesions will be evaluated according to the RECIST V1.1 standard, and categorized into complete response(CR), partial response (PR), stable disease (SD) , and progressive disease (PD).
Time frame: From screening through the last dose of treatment, each cycle is 21 days.
Progression free survival (PFS)
Tumor assessment with CT scan or MRI. The tumor lesions will be evaluated according to the RECIST V1.1 standard, and categorized into complete response(CR), partial response (PR), stable disease (SD) , and progressive disease (PD).
Time frame: From screening through the last dose of treatment, each cycle is 21 days.