A Study of KF-0210 in Advanced Solid Tumors Patients

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

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.

Study Overview

• Status: Recruiting
• Conditions: Gastric Cancer; Colorectal Cancer; Lung Cancer; Bladder Cancer; Advanced Solid Tumor; Squamous Cell Carcinoma of the Esophagus
• Intervention / Treatment: 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

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).

• Study Type: Interventional
• Enrollment (Anticipated): 64
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Xiaomei Wang, MS; Phone Number: +86-18662116821; Email: xiaomei.wang@keytherapharma.com
• Study Contact Backup: Name: Yanlin Jia, PhD; Phone Number: +1-9085145352; Email: yanlin.jia@keytherapharma.com

Study Locations

• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, 2031
      • Recruiting
      • Scientia Clinical Research Limited
      • Contact: Cosman Rasha, Doctor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / 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 Names: 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 Names: 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 Names: 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 Names: 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: Tecentriq; KF-0210-0
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: Tecentriq; KF-0210-0
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: Tecentriq; KF-0210-0

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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)

Secondary Outcome Measures

Outcome Measure	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.
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.

Collaborators and Investigators

• Sponsor: Keythera Pharmaceuticals (Australia) Pty Ltd
• Investigators: Principal Investigator: Rasha Cosman, MD, SCIENTIA Clinical Research Ltd

Study record dates

Study Major Dates

• Study Start (Actual): March 9, 2021
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: November 25, 2020
• First Submitted That Met QC Criteria: January 15, 2021
• First Posted (Actual): January 19, 2021

Study Record Updates

• Last Update Posted (Actual): September 1, 2021
• Last Update Submitted That Met QC Criteria: August 31, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Antibodies, Monoclonal; Atezolizumab
• Other Study ID Numbers: KFCS001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• 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