Clinical Trial of WBC100 on Advanced Solid Tumor

Phase 1

Recruiting

• Conditions: Solid Tumor
• Interventions: Drug: WBC100 QOD; Drug: WBC100 BID; Drug: WBC100 QD

• Registration Number: NCT05100251
• Lead Sponsor: Zhejiang University

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.

Study Timeline

• Study First Submitted: 2021-10-04
• Study First Submitted QC: 2021-10-18
• Study Start: 2021-10-25
• Study First Posted: 2021-10-29
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-21
• Last Update Posted: 2024-12-27
• Primary Completion: 2025-10-25
• Study Completion: 2025-10-25

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 90

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Once every other day (QOD)	WBC100 QOD	(1) Once every other day (QOD): after a single-dose administration (C0) and 2-day washout period, subjects will start receiving multiple doses, for 2 consecutive weeks, followed by a 1-week rest period, with 3 weeks as one treatment cycle
Twice daily (BID)	WBC100 BID	(2) Twice daily (BID): dosing for 2 consecutive weeks, followed by a 1-week rest period, with 3 weeks as one treatment cycle;
Once daily (QD)	WBC100 QD	Once daily (QD): dosing 3 consecutive weeks (with QD dosing for the first 5 days of each week followed by a 2-day rest), followed by a 1-week rest period, with a 4 weeks as one cycle

Primary Outcome Measures

Name	Time	Method
Dose limited toxicity（DLT）	28 days	safety
Frequency of Adverse Event and Severe Adverse Event	2 years	AEs and SAEs will be assessed by CTCAE v5.0
Maximum Tolerated Dose（MTD）	28 days	The highest dose level at which \< 2 of 6 subjects experienced a dose limiting toxicity during the first 28 days of the treatment period

Secondary Outcome Measures

Name	Time	Method
Tmax	28 days	Time to peak plasma concentration after one dose
AUC0-inf	28 days	Area under the plasma concentration versus time curve；time range from 0 to infinity
Vz/F	28 days	apparent volume of distribution
Duration of response (DOR)	2 years	The period from the first evaluation of complete response ( CR) or partial response (PR) to the first evaluation of progressive disease (PD)or death of any cause
Cmax	28 days	Peak plasma concentration after one dose
T1/2	28 days	half-life period
Cmin, ss	28 days	Steady minimal plasma concentration after multiple dose
λz	28 days	elimination rate constant
Cmax, ss	28 days	Steady peak plasma concentration after multiple dose
Cavg	28 days	Steady averagel plasma concentration after multiple dose
Tmax, ss	28 days	Time to steady peak plasma concentration after multiple dose
CLss/F	28 days	steady apparent clearance
Vss/F	28 days	steady apparent volume of distribution
ARCmax	28 days	Peak concerntration cumulative coefficient
Serum ferritin	28 days	change of serum ferritin
Progression-free survival (PFS)	2 years	The period from the day when the subject receives the first study treatment to the first recorded tumor progression (whether treated or not) or death of any cause, which occurs first
Objective response rate (ORR)	2 years	The number of cases in which tumor size is reduced to partial response (PR) or complete response (CR) / the total number of evaluable cases (%). In the event of partial response( PR) or complete response (CR), the subjects should confirm it no less than 4 weeks after the first evaluation
AUC0-t	28 days	Area under the plasma concentration versus time curve after one dose and multiple dose；time range from 0 to last point when plasma concentration is detectable
CL/F	28 days	apparent clearance
DF	28 days	degree of fluctuation
CA125	28 days	Change of CA125
change of tumor size	52 weeks	The major axis change of target lesion relative to baseline
ARAUC	28 days	AUC cumulative coefficient
CA19-9	28 days	Change of CA19-9

Trial Locations

Locations (1)

the First Affiliated Hospital, School of Medicine, Zhejiang University; 🇨🇳 Hangzhou, Zhejiang, China