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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Phase 1a: Cohort 1 | Experimental | KF-0210 tablet will be administered at 120 mg as a single agent orally once daily (QD) continuously in cycles (1 cycle=21 days) until the disease progression, intolerance, or informed consent withdrawal. |
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| Phase 1a: Cohort 2 | Experimental | KF-0210 tablet will be administered at 240 mg as a single agent orally once daily (QD) continuously in cycles (1 cycle=21 days) until the disease progression, intolerance, or informed consent withdrawal. |
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| Phase 1a: Cohort 3 | Experimental | KF-0210 tablet will be administered at 450 mg as a single agent orally once daily (QD) continuously in cycles (1 cycle=21 days) until the disease progression, intolerance, or informed consent withdrawal. |
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| Phase 1a: Cohort 4 | Experimental | KF-0210 tablet will be administered at 600 mg as a single agent orally once daily (QD) continuously in cycles (1 cycle=21 days) until the disease progression, intolerance, or informed consent withdrawal. |
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| Phase Ib, Cohort 1 | Experimental |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| KF-0210 tablets, 120 mg | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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. | 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. | 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) | 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 | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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). | 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. |
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Inclusion Criteria:
Age ≥ 18 years old, male and female;
Patients are confirmed by available pathology records or current biopsy having advanced, nonresectable, or recurrent and progressing solid tumors since last anti-tumor therapy, and who are unavailable or intolerable for available standard therapy or there is no standard available therapy.
Must have at least 1 measurable lesion, according RECIST V1.1 criteria (CT-scans or MRI no longer than 4 weeks before signing ICF);
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
Life expectancy≥ 3 months;
Females must not be lactating or pregnant at screening or baseline (negative pregnant test).
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Rasha Cosman, MD | Scientia Clinical Research Ltd | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Scientia Clinical Research Limited | Randwick | New South Wales | 2031 | Australia |
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KF-0210 (dose RP2D-2, orally once daily)+ Atezolizumab (1200 mg every 3 weeks) continuously until disease progression/recurrence or death from any cause, or serious adverse events (SAE) observed (whichever occurs earlier) for up to 2 years.
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| Phase Ib, Cohort 2 | Experimental | KF-0210 (dose RP2D-1, orally once daily)+ Atezolizumab (1200 mg every 3 weeks) continuously until disease progression/recurrence or death from any cause, or serious adverse events (SAE) observed (whichever occurs earlier) for up to 2 years. |
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| Phase Ib, Cohort 3 | Experimental | KF-0210 (dose RP2D, orally once daily)+ Atezolizumab (1200 mg every 3 weeks) continuously until disease progression/recurrence or death from any cause, or serious adverse events (SAE) observed (whichever occurs earlier) for up to 2 years. |
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| KF-0210 tablets, 240 mg | Drug | 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. |
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| KF-0210 tablets, 450 mg | Drug | 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. |
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| KF-0210 tablets, 600 mg | Drug | 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. |
|
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| KF-0210 (dosage RP2D-2) + Atezolizumab | Drug | 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. |
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| KF-0210 (dosage RP2D-1) + Atezolizumab | Drug | 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. |
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| KF-0210 (dosage RP2D) + Atezolizumab | Drug | 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. |
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| From screening to the end of treatment/withdrawal (up to approximately 1 year) |
| Change of Systolic pressure from Baseline [Safety] | Blood pressure measured in mmHg | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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. | 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. | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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) | 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) |
| 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). | 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). | 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). | 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). | 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). | 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). | 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. | 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 | 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. | 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. | 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). | 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). | 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). | 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). | From screening through the last dose of treatment, each cycle is 21 days. |
| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| D008175 | Lung Neoplasms |
| D000077277 | Esophageal Squamous Cell Carcinoma |
| D013274 | Stomach Neoplasms |
| D001749 | Urinary Bladder Neoplasms |
| ID | Term |
|---|---|
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002294 | Carcinoma, Squamous Cell |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D018307 | Neoplasms, Squamous Cell |
| D004938 | Esophageal Neoplasms |
| D006258 | Head and Neck Neoplasms |
| D004935 | Esophageal Diseases |
| D013272 | Stomach Diseases |
| D014571 | Urologic Neoplasms |
| D014565 | Urogenital Neoplasms |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D001745 | Urinary Bladder Diseases |
| D014570 | Urologic Diseases |
| D052801 | Male Urogenital Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C000594389 | atezolizumab |
Not provided
Not provided
Not provided