Clinical trial NCT05100251: Clinical Trial of WBC100 on Advanced Solid Tumor
Official title: An Open, Dose Escalation, Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of WBC100 in Patients with Advanced Solid Tumor
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Solid Tumor
Keywords: C-myc
Solid tumor
Lead sponsor: Zhejiang University
Sponsor class: OTHER
First posted: 2021-10-29
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is a phase I clinical study of WBC100 in Patients with advanced solid tumor.

Detailed description: This is a phase I open-label, single and dose escalation study to evaluate the safety, pharmacokinetics, and preliminary efficacy of WBC100, a drug targeting c-myc, in subjects who have been diagnosed with c-myc positive advanced solid tumor and refractory or intolerant to current standard systemic treatment.

Eligibility criteria: Inclusion Criteria:

1. Sign informed consent, able to follow protocol requirements；
2. Aged 18 to 75 years, male or female
3. （1）Dose escalation stage: Histopathology or cytology proven patients with advanced solid tumor with positive C-myc expression who have developed progressive disease or intolerability after at least one line of standard systemic therapies.（2）Dose expansion stage: Histopathology or cytology proven patients with advanced solid tumor of a selected cancer type with positive C-myc expression who have developed progressive disease or intolerability after at least one line of standard systemic therapies. Positive C-myc refers to more than 1% tumor cells are detected 1+ by immunohistochemistry (IHC) in histologic section.
4. ECOG Performance Status score: 0 to 2 points
5. Expected survival is \> 3 months
6. Adequate hematologic and organ functions (without persistent supportive treatment)

   1. Absolute Neutrophil Count \> 1.5 × 109/L, Platelet count ≥ 75 × 109/L, Hemoglobin \> 8.5 g/dL
   2. INR and PT ≤ 2 × ULN
   3. ALB \> 3.0 g/dL, Bilirubin level ≤ 2 × ULN, AST and ALT ≤ 2 × ULN or \< 5 × ULN in the presence of liver metastases
   4. Calculated creatinine clearance (e.g. Cockcroft-Gault) ≥ 60 ml/min or serum creatinine ≤ 1.5 × ULN

   f. Left ventricular ejection fraction (LVEF) ≥ 50%. Heart rate (HR) ≥ 60 bpm. QT intervals, male ≤ 450 ms, female ≤ 470 ms
7. According to RECIST 1.1, patients have at least one evaluable target lesion(only for dose expansion stage)
8. Female patients of child-bearing potential or male subjects whose spouses are women of childbearing potential must agree to use a reliable method of contraception (IUD, oral contraceptive, condom) throughout the treatment period and for 3 months after discontinuation of WBC100. Female patients of child-bearing age must undergo a serum pregnancy test before the initiation of the study and the result must be negative.

Exclusion Criteria:

1. Allergic to WBC100 or its excipients or with allergic constitution
2. Major surgery, active ulcer or unhealing wound occurred within 4 weeks before first dose
3. Taken drugs in other clinical trials within 4 weeks or still in the safety follow-up period
4. Subjects have Spinal compression, brain metastases and meningeal metastases (subjects who is asymptomatic, stable or with no need for steroid for at least 4 weeks before first dose are allowed)
5. Subjects have history of cardiac insufficiency (NYHA III-IV) or uncontrolled congestive heart failure (NYHA II-IV) within 6 months before consent
6. Subjects have risk factors of QT intervals prolongation or arrhythmia, such as Idiopathic Q-T interval prolongation syndrome or history of drug induced arrhythmia
7. Subject have any condition within 6 months before consent: unstable angina pectoris requiring surgical intervention, uncontrolled hypertension (systolic pressure ≥ 140 mmHg, diastolic pressure ≥ 90 mmHg), myocardial infarction, stroke (lacunar infarction is allowed), Coronary/peripheral artery bypass surgery, pulmonary embolism
8. Infection of HIV, active infection of HBV (HBV DNA \> 1000 IU/ml) active infection of HC (HCV-RNA ≥ upper limits of normal)
9. History of severe infection within 28 days before enrolled, including uncontrolled infection requiring systemic treatment of bacteria, virus and fungus
10. The side effects caused by the previous treatment of the subjects did not return to grade ≤1 according to CTCAE 5.0 with exception of tolerable events determined by investigator such as hair loss and grade 2 Peripheral neuropathy
11. Subjects with uncontrolled nausea or vomiting, chronic gastrointestinal diseases, unable to swallow pills, enterostomy, uncontrolled diarrhea or any intestinal surgery that cause insufficient absorption of WBC100
12. Subjects taking any strong CYP inducers or inhibitors or Chinese medicine within 7 days prior to the first dose of study drug
13. History of malignancy in the last 2 years with the exception of patients with prior history of in situ breast cancer, in situ cervical cancer, basal or squamous cell skin cancer who have already been cured
14. Subjects who have antitumor therapy within 28 days prior to first dose of WBC100, such as monoclonal antibody, chemotherapy, radiotherapy and Chinese medicine
15. Subjects have mental disorders or history of drug abuse that may limit subjects' participation in this trial
16. Unable to tolerate intravenous blood collection
17. According to the investigators' evaluation, patients are unable or unwilling to comply with the requirements of the study protocol

Primary outcomes:
measure: Frequency of Adverse Event and Severe Adverse Event
timeFrame: 2 years
measure: Dose limited toxicity（DLT）
timeFrame: 28 days
measure: Maximum Tolerated Dose（MTD）
timeFrame: 28 days
Secondary outcomes:
measure: Cmax
timeFrame: 28 days
measure: Tmax
timeFrame: 28 days
measure: AUC0-t
timeFrame: 28 days
measure: AUC0-inf
timeFrame: 28 days
measure: T1/2
timeFrame: 28 days
measure: λz
timeFrame: 28 days
measure: CL/F
timeFrame: 28 days
measure: Vz/F
timeFrame: 28 days
measure: Cmax, ss
timeFrame: 28 days
measure: Cmin, ss
timeFrame: 28 days
measure: Cavg
timeFrame: 28 days
measure: Tmax, ss
timeFrame: 28 days
measure: CLss/F
timeFrame: 28 days
measure: Vss/F
timeFrame: 28 days
measure: ARCmax
timeFrame: 28 days
measure: ARAUC
timeFrame: 28 days
measure: DF
timeFrame: 28 days
measure: CA19-9
timeFrame: 28 days
measure: CA125
timeFrame: 28 days
measure: Serum ferritin
timeFrame: 28 days
measure: Progression-free survival (PFS)
timeFrame: 2 years
measure: Duration of response (DOR)
timeFrame: 2 years
measure: Objective response rate (ORR)
timeFrame: 2 years
measure: change of tumor size
timeFrame: 52 weeks
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: the First Affiliated Hospital, School of Medicine, Zhejiang University
state: Zhejiang
Study officials:
affiliation: Zhejiang University
name: Tingbo Liang
role: PRINCIPAL_INVESTIGATOR
References: