Neoplasms

Nervous System Diseases

All Conditions

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

During the dose escalation stage, a classic "3+3" design will be used to guide dose escalation to determine MTD and RP2D. Three to six subjects are expected to be enrolled in each dose group and at least 6 subjects are enrolled in the MTD/highest dose group. The total number of subjects enrolled during the dose escalation stage will depend on the amount of DLT and the total number of dose levels explored. If DLT is not observed in the first 3 subjects enrolled for each dose level, the Safety Monitoring Committee (SMC) will review the cumulative safety data of subjects at each dose level and decide whether to proceed with dose escalation upon the completion of study treatment at least for the DLT evaluation period (28 days of Cycle 1). The dose expansion stage in this study will be initiated at the MTD or the optimal dose determined by the SMC as a fixed dose level (MTD or the optimal dose needs to be reviewed by the SMC and subjects are safe and tolerable at that dose level).

Dose Escalation Stage: Subjects will be given oral dosing of ABM-1310 twice daily (BID) for 28-day cycles of continuous administration until progressive disease (PD), unacceptable toxicity, or other withdrawal criteria are met as clinically observed.

Dose Expansion Stage: Subjects will begin to receive oral doses of ABM-1310, BID, for 28-day cycles at a fixed dose level (as determined at the dose escalation stage) until PD, unacceptable toxicity, or other withdrawal criteria are met as clinically observed.

ABM-1310

Priscilla Lee

Wenbin Li

Guodong Huang

Gang Chen

Mao Ying, Dr

Yan Qu

Qu Yan

Overall Design: This is a phase I, open-label, multicenter clinical study to evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-cancer efficacy of ABM-1310 in patients with BRAF V600-mutant relapsed and drug resistant primary malignant brain tumors.

The study including four periods of screening (28 days), treatment (no more than 2 years), safety follow-up and survival follow-up.

This study consists of two stages: dose escalation and dose expansion. During the dose escalation stage, a classic "3+3" design will be used to guide dose escalation to determine MTD and RP2D. Three to six subjects are expected to be enrolled in each dose group and at least 6 subjects are enrolled in the MTD/highest dose group. The total number of subjects enrolled during the dose escalation stage will depend on the amount of DLT and the total number of dose levels explored. If DLT is not observed in the first 3 subjects enrolled for each dose level, the Safety Monitoring Committee (SMC, including investigators, pharmacologists, and the sponsor's medical specialists, and other experienced members specially invited as necessary) will review the cumulative safety data of subjects at each dose level and decide whether to proceed with dose escalation upon the completion of study treatment at least for the DLT evaluation period (28 days of Cycle 1).

The dose expansion stage in this study will be initiated at the MTD or the optimal dose determined by the SMC as a fixed dose level (MTD or the optimal dose needs to be reviewed by the SMC and subjects are safe and tolerable at that dose level). The dose expansion stage is expected to include the following two cohorts of relapsed and drug resistant primary malignant brain tumors with BRAF V600 mutations:Cohort 1: GBM, N = up to 25 patients; Cohort 2: In addition to GBM, other primary malignant brain tumors, N = up to 15 patients.

In this study, the corresponding sample size for each cohort/tumor type may be determined according to the actual efficacy and safety data obtained. After each cohort included the first 10 patients, the available safety, efficacy, and PK data were analyzed. Based on the analysis results, the sponsor decided whether to continue recruiting patients for the study.

A Study of ABM-1310 in Patients With BRAF V600-Mutant Relapsed and Drug Resistant Primary Malignant Brain Tumors

A Phase I, Open-Label, Multicenter Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics &Preliminary Anti-Cancer Efficacy of ABM-1310 in Patients With BRAF V600-Mutant Relapsed &Drug Resistant Primary Malignant Brain Tumors

After repeated administration of ABM-1310, the drug exposure of ABM-1310 in cerebrospinal fluid was explored when the blood concentration of ABM-1310 reached stable state.

MTD is defined as the highest dose level at which DLT is observed in ≤ 1/6 subjects at one single dose group.

RP2D will be a dose either below or equal to MTD

DLT will be evaluated according to NCI-CTCAE V5.0 criteria

Safety and tolerability of ABM-1310 monotherapy

Preliminary efficacy of ABM-1310 monotherapy

Pharmacokinetic (PK) profile of ABM-1310 monotherapy

PK characteristics of repeated administration of ABM-1310 monotherapy

ABM Therapeutics Shanghai Company Limited

Symptoms and General Pathology

Rare Diseases

Recurrence

Glioma

Disease Progression

Meningioma

Ependymoma

Antineoplastic Agents

All Drugs and Chemicals

Irinotecan

Bevacizumab

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Topoisomerase I Inhibitors

Enzyme Inhibitors

125 mg/m2 non-EIAED or 340 mg/m2 EIAED every 2 weeks

Ulrik Lassen, MD., PH.D.

Irinotecan has demonstrated activity in malignant gliomas in multiple phase II studies. The activity is limited, with an approximately 15 % response rate and a progression-free survival of 3-5 months. Given the synergy between irinotecan and bevacizumab in colorectal cancer, and the high-level expression of vascular endothelial growth factor on malignant gliomas, one would expect synergy between bevacizumab and irinotecan against gliomas.

Recent data form a small study of 32 patients from Duke University have achieved a response rate of 62% in patients with malignant gliomas. Most included patients had glioblastomas, but this regimen may also have activity in more rare primary malignant brain tumors. The investigators therefore plan to include other primary malignant brain tumors in this study, and the clinical activity will be correlated with biomarkers and PET results of metabolic activity and blood flow. This may result in information that can be used to individualize therapy in the future.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of ABM-1310 in Patients With BRAF V600-Mutant Relapsed and Drug Resistant Primary Malignant Brain Tumors	NCT05892653	Primary Maligna...	ABM-1310	18 Years -	ABM Therapeutics Shanghai Company Limited
Bevacizumab and Irinotecan for Patients With Primary Brain Tumors and Progression After Standard Therapy	NCT00463203	Brain Neoplasms Glioma	Bevacizumab Irinotecan	18 Years -	Rigshospitalet, Denmark
Bevacizumab and Irinotecan for Patients With Primary Brain Tumors and Progression After Standard Therapy	NCT00463203	Brain Neoplasms Glioma	Bevacizumab Irinotecan	18 Years -	Rigshospitalet, Denmark

Spots Global Cancer Trial Database for primary malignant brain tumor