The goal of this first in human, Phase 1, multi-center, open-label, and 2-part study is to learn whether DEG6498 is safe and tolerable in participants with advanced solid tumors. It will also learn about DEG6498 pharmacokinetics (PK) profile and potential antitumor activity. The main questions it aims to answer are: * what is an appropriate dose to be given to participants? * are the side effects of treatment manageable? Participants who are treated in this study will receive DEG6498 orally once a day and be closely monitored by the treating physicians.
This study will be conducted in 2 Parts. Part 1, the dose escalation part of the study, will test different doses of DEG6498 as a single agent when administered to participants with any type of advanced solid tumor that has no available alternative treatments, and determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) for further studies. Part 2, the dose expansion part of the study, will further characterize the safety/tolerability profile and clinical activities of DEG6498 in 2 tumor types: BRAF mutant tumors and hepatocellular carcinoma (HCC).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
100
DEG6498 is an orally bioavailable molecular glue drug that potently induces the degradation of human antigen R (HuR).
Beijing Cancer Hospital
Beijing, Beijing Municipality, China
RECRUITINGBeijing GoBroad Hospital
Beijing, Beijing Municipality, China
RECRUITINGSun Yat-Sen University Cancer Center
Guangzhou, Guangdong, China
RECRUITINGIncidence of dose limiting toxicity (DLT)
Number of participants with DLT in Part 1
Time frame: From first dose through the end of Cycle 1 (each cycle is 28 days)
Incidence of adverse events (AEs) and serious AEs (SAEs) as assessed by CTCAE v5.0
Number, type, frequency, severity, timing, and relationship to DEG6498 of AEs, SAEs, etc
Time frame: From Screening up to 30 days after the last dose
Area under the concentration-time curve (AUC) of DEG6498
Measurement of plasma concentration over time for exposure to DEG6498
Time frame: From Day 1 in Cycle 1 followed by Day 1 of each treatment cycle through treatment until EOT visit, expected average 6 months (each cycle is 28 days)
Maximum concentration (Cmax) of DEG6498
Measurement of plasma concentration over time for exposure to DEG6498
Time frame: From Day 1 in Cycle 1 followed by Day 1 of each treatment cycle through treatment until EOT visit, expected average 6 months (each cycle is 28 days)
Time to reach maximum concentration (Tmax),
Measurement of plasma concentration over time for DEG6498 to reach maximum concentration
Time frame: From Day 1 in Cycle 1 followed by Day 1 of each treatment cycle through treatment until EOT visit, expected average 6 months (each cycle is 28 days)
Terminal half-life (T1/2) of DEG6498
Measurement of the clearance of DEG6498 from plasma over time
Time frame: From Day 1 in Cycle 1 followed by Day 1 of each treatment cycle through treatment until EOT visit, expected average 6 months (each cycle is 28 days)
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Clearance following oral dose (CL/F) of DEG6498
Measurement of the clearance of DEG6498 from plasma over time
Time frame: From Day 1 in Cycle 1 followed by Day 1 of each treatment cycle through treatment until EOT visit, expected average 6 months (each cycle is 28 days)
Overall response rate (ORR)
The proportion of participants with best overall response of complete response (CR) or partial response (PR) as determined by the Investigator per RECIST 1.1
Time frame: From the date of dosing until the date of first documented progression, unacceptable toxicity, death from any cause, participant withdraw consent, or investigator's decision, whichever occurs first, expected up to 30 months
Time to response (TTR)
The time interval from the first DEG6498 dose date to the date of first documented objective response
Time frame: From the date of dosing until the date of first documented progression, unacceptable toxicity, death from any cause, participant withdraw consent, or investigator's decision, whichever occurs first, expected up to 30 months
Disease control rate (DCR)
The proportion of participants with a best ORR + Stable Disease (SD)
Time frame: From the date of dosing until the date of first documented progression, unacceptable toxicity, death from any cause, participant withdraw consent, or investigator's decision, whichever occurs first, expected up to 30 months
Duration of response (DOR)
The time interval from the earliest occurrence of a documented objective response to the first time of disease progression or death from any cause, whichever comes first
Time frame: From the date of dosing until the date of first documented progression, unacceptable toxicity, death from any cause, participant withdraw consent, or investigator's decision, whichever occurs first, expected up to 30 months