Solid Tumors
Conditions
Interventions
Part 1: Dose Escalation:The initial dose of DEG6498 is 0.03 mg, once daily (QD), with a treatment cycle of 28 days. It is administered continuously for the first 21 days and discontinued for the next
Part 2: Dose Expansion:Part 1 results will inform the DEG6498 dose level to be used in Part 2 of the study.
Sponsors
Sun Yat-sen University Cancer Center
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Willing and able to provide written informed consent for the study prior to the performance of any study-specific procedures; 2. Male and female older than or equal to 18 years of age at the time signing the informed consent form (ICF); 3. If female, must be postmenopausal, or surgically sterile, or agree to highly effective contraceptive measures to prevent pregnancy throughout treatment period and within 30 days of last study drug treatment a. Postmenopausal women must be amenorrheic for at least 12 months in order not to be considered of childbearing potential. Postmenopausal status will be confirmed by measurement of follicle-stimulating hormone (FSH). 4. Women of childbearing potential (WOCBP) must: a. Have 2 negative pregnancy tests (1 serum test required) as verified by the investigator prior to starting study drug; b. Agree to highly effective contraceptive measures to prevent pregnancy throughout treatment period and within 30 days of last study drug treatment ; c. Agrees to ongoing pregnancy testing during the course of the study; 5. If male, must: a. Practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a WOCBP while on the study and for at least 30 days following DEG6498 discontinuation; b. Agree to inform and ensure their female partners to use highly effective contraception measures to prevent pregnancy; c. Agree to refrain from donating sperm while on study drug and for at least 30 days following DEG6498 discontinuation; 6. Patients with advanced solid tumors, who have progressed despite standard therapies, are intolerant of standard therapy, or for whom no standard therapy exists; a. Part 1: Advanced solid tumor patients; b. Part 2: Patients with BRAF V600 (Class 1) mutation positive tumors and HCC Patients; i. BRAF mutation patents: previous local testing results on BRAF V600 (Class 1) mutation acceptable for screening; however, must be confirmed by a Sponsor-approved lab prior to dosing start; ii. For HCC patients; 1) Diagnosis of advanced HCC according to the AASLD Guidelines; 2) HCC stage C according to the BCLC staging classification; 3) Current cirrhotic status of Child-Pugh class A (5-6 points), with no encephalopathy and/or ascites. Child-Pugh status must be calculated based on clinical findings and laboratory results during the Screening period. 7. Presence of at least 1 measurable lesion according to RECIST v1.1. For HCC patients, lesions previously treated with loco-regional therapy, such as radiation therapy, hepatic arterial embolization, radiofrequency ablation, and percutaneous interventional therapy should not be considered measurable unless progression is noted at baseline. 8. Has an ECOG performance status of 0 or 1; 9. Adequate end organ function within 28 days of the first dose of study drug; 10. Participants must have the following laboratory values; a. Hemoglobin >=8.0 g/dL; b. ANC >=1500/µL without growth factor support for more than 14 days; c. PLT >=75×1E9/mL without transfusion for more than 7 days; d. PT/INR =60 mL/min (by Cockcroft-Gault); 11. Left ventricular ejection fraction (LVEF) >=50%.
Exclusion criteria
Exclusion criteria: 1. Participant has a significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the participant from participating in the study, puts the participant at unacceptable risk if he/she were to participate in the study; 2. Participant has a condition that confounds the ability for interpret data from the study; 3. Pregnant or breastfeeding women; 4. Active or concurrent malignancy requiring treatment (including both systemic therapy and radiotherapy) within 14 days or 5 half lives (whichever is shorter) prior to the first dose of study drug, or received antibody therapy within 28 days; 5. Clinically significant pleural effusion that either required tapping or is associated with shortness of breath 6. Symptomatic CNS metastases which are neurologically unstable, or CNS metastases requiring local CNS directed therapy, or increasing doses of corticosteroids within 2 weeks of first dose of study treatment. 7. Clinically significant cardiovascular disease: a. History or current symptoms of heart failure Grade III or Grade IV according to the New York Heart Association (NYHA) classification; b. Myocardial infarction or unstable angina within 6 months of the first dose of study drug c. Uncontrolled hypertension (Grade >=3); d. Clinically significant, uncontrolled arrhythmia, including bradyarrhythmia; e. Unstable angina or new onset angina within 3 months of the first dose of study drug; f. Pericarditis or myocarditis; g. Complete left bundle branch or other clinically significant abnormal ECG at screening. 8. QT interval corrected using Fridericia’s formula (QTcF) >470 msec. Participant has a history or familial history of prolonged QT syndrome or history of torsades de pointes; 9. History of brain aneurysm or stroke; 10. Anemia requiring transfusion; 11. Major surgical procedure within 30 days of the first dose of study drug (procedures such as central venous catheter placement and tumor needle biopsy are not considered major surgical procedures). Note: participant must have recovered from any clinically significant effects of the recent surgery; 12. History of severe respiratory compromise requiring oxygen, respiratory support (example bilevel positive airway pressure [biPAP] or continuous positive airway pressure [CPAP]) or a history of aspiration pneumonia requiring hospitalization; 13. Known active or chronic infection that requires systemic therapy within 2 weeks of first dose of study drug; 14. Significant gastrointestinal diseases that may significantly alter the absorption of the study drug; 15. Ongoing significant viral illness or pneumonia within 2 weeks of screening; 16. Known human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome; 17. Active HBV or HCV infection. Patients whose disease is controlled under antiviral; therapy can be included. Active or uncontrolled HBV or HCV infection is defined as follows: a. Combination of HBV deoxyribonucleic acid (DNA) >1000 IU/mL or >2500 copies/mL plus positive Hepatitis B surface antigen (HBsAg) plus positive Hepatitis B core antibody (HBcAg), or b. Combination of HBV DNA >1000 IU/mL or >2500 copies/mL plus positive HBsAg, or c. Combination of HBV DNA >1000 IU/mL or >2500 copies/mL plus positive HBcAg, or d. Positive serum HCV ribonucleic acid (RNA) and antibody to HCV (HCV Ab). 18. Active tuberculosis infection; 19. History of kidney disease requiring dialysis; 20. Has received immune suppressive medication within 14 days
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The safety and tolerability of DEG6498 in participants with advanced solid tumors;The MTD and/or RP2D of DEG6498; | — |
Secondary
| Measure | Time frame |
|---|---|
| The pharmacokinetic (PK) profile of DEG6498 and DEG6498 R and S enantiomers ;Potential antitumor activity of DEG6498 in participants with Part 1: advanced solid tumors Part 2: BRAF mutant tumors or HCC; | — |
Countries
China
Contacts
Public ContactLi Zhang
Sun Yat-Sen University Cancer Center
Outcome results
None listed