IN10018 in Combination With Dalpiciclib for Progressive Meningiomas
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorCapital Medical University
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
World Health Organization (WHO) Grade 2 or Grade 3 meningioma; or
WHO Grade 1 meningioma that has recurred after surgery or radiotherapy and demonstrates clear radiographic or clinical progression, as determined by the investigator.
Hemoglobin of at least 100 g/L, without dependence on red blood cell transfusion or erythropoietin.
Platelet count of at least 100 × 10^9/L, without dependence on platelet transfusion.
Disqualifiers
Left ventricular ejection fraction below 50%;
Corrected QT interval greater than 480 milliseconds;
New York Heart Association functional class 2 or higher;
History of serious arrhythmia or cardiomyopathy. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage. Participants with small-volume effusions detectable only by imaging may be considered eligible.
Trial design
Design model
Single group
Treatments tested in this trial
Ifebemtinib
DrugIfebemtinib (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
DrugDalpiciclib 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.
Treatment groups
24 Participants
are divided into 1 treatment groupGroup A: IN10018 Plus DalpiciclibExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Incidence 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).2
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.Secondary outcomes
1
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.2
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.3
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.4
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.Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Source ClinicalTrials.gov