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A Study of KF-0210 in Advanced Solid Tumors Patients

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ClinicalTrials.gov Identifier: NCT04713891
Recruitment Status : Recruiting
First Posted : January 19, 2021
Last Update Posted : January 26, 2021
Sponsor:
Information provided by (Responsible Party):
Keythera (Suzhou) Pharmaceuticals Co. Ltd ( Keythera Pharmaceuticals (Australia) Pty Ltd )

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumor Colorectal Cancer Lung Cancer Squamous Cell Carcinoma of the Esophagus Gastric Cancer Bladder Cancer Drug: KF-0210 tablets, 120 mg Drug: KF-0210 tablets, 240 mg Drug: KF-0210 tablets, 450 mg Drug: KF-0210 tablets, 600 mg Drug: KF-0210 (dosage RP2D-2) + Atezolizumab Drug: KF-0210 (dosage RP2D-1) + Atezolizumab Drug: KF-0210 (dosage RP2D) + Atezolizumab Phase 1

Detailed Description:

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).

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 64 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I, Multi-Center, Open-Label Study to Evaluate the Safety and Tolerability, Pharmacokinetics, Pharmacodynamics and Anti-tumor Activity of KF-0210 in Patients With Advanced Solid Tumors
Estimated Study Start Date : January 25, 2021
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : December 31, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Phase 1a: Cohort 1
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.
Drug: KF-0210 tablets, 120 mg
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.
Other Name: KF-0210-0

Experimental: Phase 1a: Cohort 2
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.
Drug: KF-0210 tablets, 240 mg
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.
Other Name: KF-0210-0

Experimental: Phase 1a: Cohort 3
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.
Drug: KF-0210 tablets, 450 mg
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.
Other Name: KF-0210-0

Experimental: Phase 1a: Cohort 4
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.
Drug: KF-0210 tablets, 600 mg
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.
Other Name: KF-0210-0

Experimental: Phase Ib, Cohort 1
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.
Drug: KF-0210 (dosage RP2D-2) + Atezolizumab
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.
Other Names:
  • KF-0210-0
  • Tecentriq

Experimental: Phase Ib, Cohort 2
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.
Drug: KF-0210 (dosage RP2D-1) + Atezolizumab
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.
Other Names:
  • KF-0210-0
  • Tecentriq

Experimental: Phase Ib, Cohort 3
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.
Drug: KF-0210 (dosage RP2D) + Atezolizumab
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.
Other Names:
  • KF-0210-0
  • Tecentriq




Primary Outcome Measures :
  1. Percentage of patient with adverse events / serious adverse events (AEs/SAEs) [Safety and Tolerability] [ 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)) ]
    Adverse events will be assessed according to CTCAE V5.0, and be coded according to the MedDRA Dictionary

  2. Dose limiting toxicity (DLT) of KF-0210 [Tolerability] [ Time Frame: From Cycle 1 Day 1 to Cycle 1 Day 21, each cycle is 21 days. ]
    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.

  3. Maximum tolerated dose (MTD) of KF-0210 alone [Tolerability] [ Time Frame: Up to 21 days after first administration in cycle 1, each cycle is 21 days ]
    The Maximum tolerated dose (MTD) is defined as the highest dose at which ≤1、6 participants occurred dose limiting toxicity at each dose level.

  4. Change of Body Weight from Baseline [Safety] [ 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) ]
    Body Weight measured in kilogram (kg)

  5. Change of Body Temperature from Baseline [Safety] [ Time Frame: From screening to the end of treatment/withdrawal (up to approximately 1 year) ]
    Axillary temperature measured in celsius

  6. Change of Pulse rate from Baseline [Safety] [ Time Frame: From screening to the end of treatment/withdrawal (up to approximately 1 year) ]
    Pulse rate measured per minute

  7. Change of Systolic pressure from Baseline [Safety] [ Time Frame: From screening to the end of treatment/withdrawal (up to approximately 1 year) ]
    Blood pressure measured in mmHg

  8. Change of Diastolic pressure from Baseline [Safety] [ Time Frame: From screening to the end of treatment/withdrawal (up to approximately 1 year) ]
    Blood pressure measured in mmHg

  9. Change of Heart rate from Baseline [Safety] [ Time Frame: From screening to the end of treatment/withdrawal (up to approximately 1 year) ]
    Heart rate in beats per minute (Bpm) through 12-lead ECG assessment

  10. Change of R-R interval from Baseline [Safety] [ Time Frame: From screening to the end of treatment/withdrawal (up to approximately 1 year) ]
    R-R interval measured in millisecond through 12-lead ECG assessment

  11. Change of P-R interval from Baseline [Safety] [ Time Frame: From screening to the end of treatment/withdrawal (up to approximately 1 year) ]
    P-R interval measured in millisecond through 12-lead ECG assessment

  12. Change of QRS complex from Baseline [Safety] [ Time Frame: From screening to the end of treatment/withdrawal (up to approximately 1 year) ]
    QRS complex measured in millisecond through 12-lead ECG assessment

  13. Chang of QT interval from Baseline [Safety] [ Time Frame: From screening to the end of treatment/withdrawal (up to approximately 1 year) ]
    QT interval measured in millisecond through 12-lead ECG assessment

  14. Change of corrected QT (QTc) interval from Baseline [Safety] [ Time Frame: From screening to the end of treatment/withdrawal (up to approximately 1 year) ]
    corrected QT (QTc) interval measured in millisecond through 12-lead ECG assessment

  15. Change of Fridericia's Correction QT (QTcF) interval from Baseline [Safety] [ Time Frame: From screening to the end of treatment/withdrawal (up to approximately 1 year) ]
    Fridericia's Correction QT (QTcF) interval measured in millisecond through 12-lead ECG assessment.

  16. Change of Eastern Cooperative Oncology Group-Performance Status (ECOG PS) from Baseline [Safety] [ 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) ]
    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.

  17. Change of Total Protein (TP) from Baseline [Safety] [ 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) ]
    Total Protein (TP) measured in g/dL

  18. Change of Albumin (ALB) from Baseline [Safety] [ 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) ]
    Albumin(ALB) measured in g/dL

  19. Change of Alanine aminotransferase (ALT) from Baseline [Safety] [ 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) ]
    Alanine aminotransferase (ALT) measured in IU/L

  20. Change of Aspartate aminotransferase (AST) from Baseline [Safety] [ 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) ]
    Aspartate aminotransferase (AST) measured in IU/L

  21. Change of Alkaline phosphatase (ALP/AKP) from Baseline [Safety] [ 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) ]
    Alkaline phosphatase (ALP/AKP) measured in IU/L

  22. Change of Total bilirubin from Baseline [Safety] [ 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) ]
    Total bilirubin measured in mg/dL

  23. Change of Direct bilirubin from Baseline [Safety] [ 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) ]
    Direct bilirubin measured in mg/dL

  24. Change of Indirect bilirubin from Baseline [Safety] [ 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) ]
    Indirect bilirubin measured in mg/dL

  25. Change of Glutamyl transpeptidase from Baseline [Safety] [ 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) ]
    Glutamyl transpeptidase measured in U/L

  26. Change of Blood glucose from Baseline [Safety] [ 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) ]
    Blood glucose measured in mg/dL

  27. Change of Urea from Baseline [Safety] [ 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) ]
    Urea measured in mg/dL

  28. Change of Uric acid from Baseline [Safety] [ 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) ]
    Uric acid measured in mg/dL

  29. Change of Creatinine from Baseline [Safety] [ 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) ]
    Creatinine measured in mg/dL

  30. Change of Creatinine Kinase from Baseline [Safety] [ 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) ]
    Creatinine Kinase measured in IU/L

  31. Change of Total Cholesterol from Baseline [Safety] [ 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) ]
    Total Cholesterol measured in mmol/L

  32. Change of Triglycerides from Baseline [Safety] [ 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) ]
    Triglycerides measured in mmol/L

  33. Change of Potassium, Sodium, Chloride or Calcium from Baseline [Safety] [ 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) ]
    Potassium, Sodium, Chloride or Calcium measured in mmol/dL

  34. Change of Leukocyte Count from Baseline [Safety] [ 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) ]
    Leukocyte Count measured in K/uL

  35. Change of Neutrophil Count from Baseline [Safety] [ 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) ]
    Neutrophil Count in K/uL

  36. Change of Percentage of Neutrophil from Baseline [Safety] [ 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) ]
    Percentage of Neutrophil will be measured

  37. Change of Lymphocyte Count from Baseline [Safety] [ 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) ]
    Lymphocyte Count measured in K/uL

  38. Change of Percentage of Lymphocyte from Baseline [Safety] [ 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) ]
    Percentage of Lymphocyte will be measured

  39. Change of Monocytes Count from Baseline [Safety] [ 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) ]
    Monocytes Count measured in K/uL

  40. Change of Percentage of Monocytes from Baseline [Safety] [ 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) ]
    Percentage of Monocytes will be measured

  41. Change of Eosinophils Count from Baseline [Safety] [ 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) ]
    Eosinophils Count measured in K/uL

  42. Change of Percentage of Eosinophils from Baseline [Safety] [ 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) ]
    Percentage of Eosinophils will be measured

  43. Change of Basophil Count from Baseline [Safety] [ 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) ]
    Basophil Count measured in K/uL

  44. Change of Percentage of Basophil from Baseline [Safety] [ 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) ]
    Percentage of Basophil will be measured

  45. Change of Erythrocyte Count from Baseline [Safety] [ 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) ]
    Erythrocyte Count measured in K/uL

  46. Change of Hemoglobin from Baseline [Safety] [ 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) ]
    Hemoglobin measured in mg/dL

  47. Change of Hematocrit Platelets from Baseline [Safety] [ 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) ]
    Hematocrit Platelets measured in K/uL

  48. Change of Coagulation test-Activated partial thromboplastin time (APTT) from Baseline [Safety] [ 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) ]
    Activated partial thromboplastin time (APTT) measured in seconds

  49. Change of Coagulation test-Prothrombin time (PT) from Baseline [Safety] [ 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) ]
    Prothrombin time (PT) measured in seconds

  50. Change of Coagulation test-Fibrinogen(FIB) from Baseline [Safety] [ 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) ]
    Fibrinogen(FIB) measured in mmol/L

  51. Change of Coagulation test-Thrombin time (TT) from Baseline [Safety] [ 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) ]
    Thrombin time (TT) measured in seconds

  52. Change of Urine pH from Baseline [Safety] [ 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) ]
    pH value will be measured

  53. Change of Specific gravity of urine from Baseline [Safety] [ 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) ]
    Specific gravity value will be measured

  54. Change in Occult blood result from Baseline [Safety] [ 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) ]
    The result will be recorded as either positive or negative

  55. Change in Urine Bilirubin result from Baseline [Safety] [ 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) ]
    Urine bilirubin will be measure in µmol/L

  56. Change in Urine protein from Baseline [Safety] [ 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) ]
    Urine protein will be measured in mg/dL

  57. Change in Urine Glucose from Baseline [Safety] [ 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) ]
    Urine Glucose will be measured in mg/dL

  58. Change in Ketones from Baseline [Safety] [ 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) ]
    Ketones will be measured in mg/dL

  59. Change in Urobilinogen from Baseline [Safety] [ 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) ]
    Urobilinogen will be measured in EU/dL

  60. Change in Urinary leukocyte from Baseline [Safety] [ 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) ]
    Urinary leukocyte will be counted in K/uL

  61. Change in Urine erythrocytes from Baseline [Safety] [ 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) ]
    Urine erythrocytes will be counted in K/uL

  62. Change in Urine Nitrites from Baseline [Safety] [ 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) ]
    Urobilinogen will be measured in mg/dL

  63. Clinically significant abnormality in physical examinations [ 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) ]
    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)


Secondary Outcome Measures :
  1. Maximum observed plasma concentration (Cmax) [ 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. ]
    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).

  2. Time of maximum plasma concentration (Tmax) [ 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. ]
    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).

  3. Area under the plasma concentration-time curve from time-zero extrapolated to infinite time (AUC0-inf) [ 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. ]
    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).

  4. Area under the plasma concentration-time curve from time-zero to the time of the last measurable concentration (AUC0-t) of KF-0210 [ 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. ]
    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).

  5. Terminal half-life (T1/2) of KF-0210 [ 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. ]
    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).

  6. Accumulation ratio (Rac) [ 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. ]
    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).

  7. Cmin to Cmax fluctuation between dose time and Tau (DF) [ 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. ]
    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).

  8. Blood cytokines/chemokines levels [ Time Frame: Up to 21 days after first administration in cycle 1, each cycle is 21 days. ]
    Biomarker for pharmacodynamic assessment including interferon (IFN-γ), tumor necrosis factor (TNF-α), CXCL10 and CCL5.

  9. Urine prostaglandin metabolites level [ Time Frame: Up to 21 days after first administration in cycle 1, each cycle is 21 days. ]
    To explore the prostaglandin metabolites in urine

  10. Tumor T cell infiltration [ Time Frame: Up to 21 days after first administration in cycle 1, each cycle is 21 days. ]
    Tumor biopsies will be analyzed by immunohistochemistry (IHC) for CD3+ T cells, CD8+ T cells and PD-L1 expression.

  11. Change in tumor size from baseline [ Time Frame: From screening through the last dose of treatment, each cycle is 21 days. ]
    Tumor assessment with CT scan or MRI. The anti-tumor activity will be evaluated according to the RECIST V1.1.

  12. Objective response rate (ORR) [ Time Frame: From screening through the last dose of treatment, each cycle is 21 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).

  13. Duration of response (DOR) (days) [ Time Frame: From screening through the last dose of treatment, each cycle is 21 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).

  14. Disease control rate (DCR) [ Time Frame: From screening through the last dose of treatment, each cycle is 21 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).

  15. Progression free survival (PFS) [ Time Frame: From screening through the last dose of treatment, each cycle is 21 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).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥ 18 years old, male and female;
  2. 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.

    • Phase Ia (Dose Escalation): Advanced solid tumors;
    • Phase Ib (Expansion Study): Patients must have any of the following tumor type and have not participated in Phase Ia trial of this study: CRC (MSS), LC, SCCE, GC, and BC. Among them, patients with LC, SCCE, or GC must have undergone PD-1/PD-L1 treatment for at least 12 weeks and failed.
  3. Must have at least 1 measurable lesion, according RECIST V1.1 criteria (CT-scans or MRI no longer than 4 weeks before signing ICF);
  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
  5. Life expectancy≥ 3 months;
  6. Females must not be lactating or pregnant at screening or baseline (negative pregnant test).

Exclusion Criteria:

  1. Patients with prior anti-tumor therapy within 4 weeks prior to first dosing of KF-0210, including chemotherapy, biotherapy, endocrine therapy and immunotherapy (tumor vaccine, cytokine, or growth factor given to control the cancer);
  2. Patients with prior definitive radiation therapy within 6 weeks prior to first dosing of KF-0210, and the irradiated lesions showed no signs of progression if it to be considered target lesions. Or patients with prior palliative radiotherapy within 2 weeks prior to first dosing of KF-0210. Or the radiotherapy-related side effects have unresolved before the study entry. Or use of radiopharmaceuticals (strontium, samarium) within 8 weeks prior to first dosing of KF-0210;
  3. Patients who have another active malignancy which is likely to require treatment;
  4. Patients who have known active central nervous system (CNS) metastases and/or carcinomatous meningitis;
  5. Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, uncontrolled arterial hypertension, unstable angina, myocardial infarction, or stroke within 6 months prior to the first dose of KF-0210; or cardiac arrhythmia requiring medical treatment (including oral anticoagulation);
  6. Patients with any active autoimmune disease or a documented history of autoimmune disease, poorly controlled asthma or history of syndrome that required systemic steroids or immunosuppressive medications, except for patients with vitiligo or resolved childhood asthma/atopy. Patients with asthma who require intermittent use of bronchodilators (such as albuterol) will not be excluded from this study;
  7. Patients with inflammatory bowel disease or digestive tract diseases (e.g. peptic ulcer disease, including stomach and duodenal ulcer, gastritis and enteritis);
  8. Inability to take oral medication, or malabsorption syndrome or any other uncontrolled gastrointestinal condition (e.g., nausea, diarrhea, or vomiting) that might impair the bioavailability of KF-0210;
  9. Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids except inhaled or intranasal corticosteroids (with minimal systemic absorption);
  10. Current use of NSAIDs, COX-1/COX-2 inhibitors within 4 weeks;
  11. Patients who have received surgical or interventional treatment (excluding tumor biopsy, puncture, etc.) within 28 days prior to first dosing of KF-0210;
  12. Use of other investigational drugs within 28 days or at least 5 half-lives (whichever is shorter) prior to the first dosing of KF-0210;
  13. Use of any live vaccines (e.g., intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella, and TY21a typhoid vaccines) within 28 days prior to the first dosing of KF-0210;
  14. Any unresolved toxicities from prior therapy, greater than Common Terminology Criteria for Adverse Events (CTCAE 5.0) grade 1 at the time of starting study treatment with exception of alopecia;
  15. Any uncontrolled or severe illness, including but not limited to: ongoing or active infection requiring parenteral antibiotics;
  16. Positive screening tests for any one of them: human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen (HBsAg); hepatitis B core antibody (HBcAb) (negative for HBsAg, but HBcAb positive, an HBV-DNA test will be performed and if positive will be excluded), hepatitis C antibody (anti-HCV positive, but negative HCV RNA test is allowed to be included).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04713891


Contacts
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Contact: Xiaomei Wang, MS +86-18662116821 xiaomei.wang@keytherapharma.com
Contact: Yanlin Jia, PhD +1-9085145352 yanlin.jia@keytherapharma.com

Locations
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Australia, New South Wales
Scientia Clinical Research Limited Recruiting
Randwick, New South Wales, Australia, 2031
Contact: Cosman Rasha, Doctor         
Sponsors and Collaborators
Keythera Pharmaceuticals (Australia) Pty Ltd
Investigators
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Principal Investigator: Rasha Cosman, MD Scientia Clinical Research Ltd
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Responsible Party: Keythera Pharmaceuticals (Australia) Pty Ltd
ClinicalTrials.gov Identifier: NCT04713891    
Other Study ID Numbers: KFCS001
First Posted: January 19, 2021    Key Record Dates
Last Update Posted: January 26, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Esophageal Neoplasms
Esophageal Squamous Cell Carcinoma
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Carcinoma, Squamous Cell
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Head and Neck Neoplasms
Esophageal Diseases
Atezolizumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs