Advanced Solid Tumors With MAPK Signal Pathway Mutant Clinical Trial
Official title:
A Phase I/II Clinical Study to Evaluate The Safety, Tolerability, Pharmacokinetics, And Pharmcodynamics of Oral Administration of GH55 in Patients With MAPK Mutant Advanced Solid Tumors
This is a multi-center, open-label, dose escalation phase I and dose expansion phase II study aimed to evaluate the safety, tolerability, PK and PD profiles as well as to observe the efficacy of GH55 in patients with MAPK mutant advanced solid tumors. This study is divided into two parts, namely the dose escalation phase I study and the dose expansion phase II study.
This study is divided into two parts, namely the dose escalation phase I study and the dose expansion phase II study. This study plans to include 5 dose groups, namely 40 mg, 80 mg, 150 mg, 200 mg, and 250 mg, and adopts a "3+3" dose escalation design. All of the 40 mg, 80 mg, 150 mg, 200 mg and 250 mg groups will adopt the "3+3" design, and 3-6 subjects will be enrolled in each group. The enrollment of the first subject and subsequent subject in each dose group should be at least 7 days apart. Subjects will receive a single dose of GH55 on day 1 (Cycle 0 Day 1, C0D1). The investigator will assess the safety data on day 3 (C0D3) to determine whether subjects can be initiated on multiple doses of GH55 [quaque die (QD) continuously, and 3 weeks per cycle] on day 4 (C1D1). The dose limiting toxicity (DLT) observation period is from the initiation of single dosing to the end of the first cycle of multiple dosing [Cycle 0 (3 days) and Cycle 1 (3 weeks)]. The sponsor and investigator will jointly assess the safety data to determine whether to ascend to the next higher dose. These steps will be repeated until MTD is reached, and the safety, tolerability, and PK profile of single dose and multiple doses of oral administration of GH55 will be assessed. If MTD cannot be determined when the dose escalation study is complete, the sponsor and investigator will jointly determine whether to increase the ascending dose based on the existing safety, tolerability, PK, PD and preliminary efficacy data. All subjects can continue the treatment until disease progression, initiation of new antitumor treatment, withdrawal of informed consent, or death (whichever occurs first). The dose expansion phase II study will begin once the last subject in the dose escalation phase I study has completed the DLT observation. Two dose expansion groups will be designed, with a dose level in each group that is expected to become the RP2D based on the safety, tolerability, PK/PD profile, and preliminary efficacy data of GH55 in the dose escalation phase I study. Two dose expansion groups will enroll 60-80 subjects to further evaluate the efficacy, safety, and PK/PD profile of GH55 in patients with advanced solid tumors. ;