This open-label Phase Ib study will evaluate the safety, tolerability, and preliminary effectiveness of IN10018 in combination with dalpiciclib in adults with progressive meningiomas. Progressive meningiomas are tumors arising from the membranes surrounding the brain that have continued to grow or have returned after previous treatment. Participants will receive both study drugs by mouth in 28-day treatment cycles. IN10018 will be taken once daily throughout each cycle, and dalpiciclib will be taken once daily for 21 days followed by 7 days without dalpiciclib. Treatment may continue until the tumor progresses, unacceptable side effects occur, or another reason for stopping treatment applies. The study includes a dose-confirmation phase and a dose-expansion phase. The main goals are to evaluate side effects and determine a recommended dose of the combination for further study. Researchers will also assess whether the treatment can shrink tumors or delay tumor growth, measure how the drugs are processed in the body, and explore tumor and blood biomarkers that may be associated with treatment response.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
24
Ifebemtinib (IN10018) is an investigational oral focal adhesion kinase inhibitor. It will be administered once daily continuously during each 28-day treatment cycle. The starting dose is 100 mg once daily. If the starting dose is not tolerated, the dose may be reduced to 50 mg once daily. Ifebemtinib will be administered in combination with dalpiciclib until disease progression, unacceptable toxicity, withdrawal of consent, or another protocol-defined discontinuation criterion.
Dalpiciclib is an oral, selective cyclin-dependent kinase 4 and 6 inhibitor. It will be administered at a starting dose of 125 mg once daily on Days 1 through 21 of each 28-day treatment cycle, followed by 7 days without dalpiciclib. If the starting dose is not tolerated, the dose may be reduced to 100 mg once daily. Dalpiciclib will be administered in combination with ifebemtinib until disease progression, unacceptable toxicity, withdrawal of consent, or another protocol-defined discontinuation criterion.
Beijing Sanbo Brain Hospital, Capital Medical University
Beijing, Beijing Municipality, China
RECRUITINGSanbo Brain Hospital, Capital Medical University
Beijing, China
NOT_YET_RECRUITINGIncidence of Dose-Limiting Toxicities (DLTs)
The number and percentage of participants who experience at least one protocol-defined dose-limiting toxicity during Cycle 1. Dose-limiting toxicities will be assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0, and must be considered related to IN10018 and/or dalpiciclib.
Time frame: Dose-limiting toxicities will be assessed at the end of Cycle 1 (each cycle is 28 days).
Incidence of Treatment-Emergent Adverse Events
Number and percentage of participants who experience treatment-emergent adverse events, treatment-related adverse events, serious adverse events, Grade 3 or higher adverse events, or adverse events resulting in treatment interruption, dose reduction, or permanent treatment discontinuation. Adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.
Time frame: Adverse events will be assessed from the first dose through 30 days after the last dose of study treatment, up to approximately 24 months.
Objective Response Rate (ORR)
Percentage of participants with a best overall response of complete response or partial response according to RANO for Meningioma.
Time frame: From first dose until disease progression, initiation of new anticancer therapy, withdrawal, death, or study completion, up to 36 months.
Six-Month Progression-Free Survival Rate (PFS-6)
Percentage of participants alive without radiographic disease progression at 6 months after the first dose of study treatment.
Time frame: At 6 months after the first dose.
Disease Control Rate (DCR)
Percentage of participants achieving CR, PR, minor response (MR), or stable disease (SD) lasting at least 8 weeks.
Time frame: From first dose until disease progression, withdrawal, death, or study completion, up to 36 months.
Duration of Response (DoR)
Time from the first documented objective response (CR or PR) until disease progression or death from any cause.
Time frame: From first documented response until disease progression or death, up to 36 months.
Progression-Free Survival (PFS)
Time from the first dose of study treatment until radiographic disease progression according to RANO criteria or death from any cause.
Time frame: From first dose until disease progression or death, up to 36 months.
Overall Survival (OS)
Time from the first dose of study treatment until death from any cause.
Time frame: From first dose until death from any cause, up to 36 months.
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