Clinical Trial of WBC100 on Advanced Solid Tumor

Zhejiang University

Status and phase: Enrolling; Phase 1

Conditions: Solid Tumor

Treatments: Drug: WBC100 QD; Drug: WBC100 QOD; Drug: WBC100 BID

Study type: Interventional

Funder types: Other

Identifiers

NCT05100251

WBC100

Details and patient eligibility

About

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

Full 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.

Enrollment: 90 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Sequential Assignment

Masking: None (Open label)

---

90 participants in 3 patient groups

Once every other day (QOD)

Experimental group

Description:

(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

Treatment:

Drug: WBC100 QOD

Twice daily (BID)

Experimental group

Description:

(2) Twice daily (BID): dosing for 2 consecutive weeks, followed by a 1-week rest period, with 3 weeks as one treatment cycle;

Treatment:

Drug: WBC100 BID

Once daily (QD)

Experimental group

Description:

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

Treatment:

Drug: WBC100 QD