A Study of ABM-1310 in Patients With BRAF V600-Mutant Relapsed and Drug Resistant Primary Maligna… (NCT05892653) | Clinical Trial Compass
TerminatedPhase 1
A Study of ABM-1310 in Patients With BRAF V600-Mutant Relapsed and Drug Resistant Primary Malignant Brain Tumors
Stopped: Adjustment of the applicant's research and development strategy
China15 participantsStarted 2023-06-30
Plain-language summary
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.
Who can participate
Age range18 Years
SexALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria
✓. Subjects who are able to understand and voluntarily sign informed consent forms (ICFs).
✓. Male and female subjects at the age of ≥18 at the time of screening.
✓. Patients with histologically or cytologically-confirmed, primary malignant brain tumor with (a) failure of prior standard therapy, (b) no standard therapy available, or (c) for whom standard therapy is not applicable considered by the patient or treating physician, or (d) intolerance to standard treatment. Subjects who were previously treated with BRAF and/or MEK inhibitors are allowed to be enrolled in this study.
✓. Documentation of positive BRAF V600 mutation is required for enrollment. It is recommended to provide sufficient fresh/archived tumor tissue samples (formalin-fixed paraffin-embedded tumor specimens \[preferred\]) or 5-10 available unstained sections of good quality for verification of BRAF V600 mutation status at the central laboratory. For any subject who is unable to provide suitable and adequate tumor specimens, re-biopsy (with controllable safety) can be performed in a non-mandatory manner if it is feasible as assessed by the investigator and the subject gives informed consent; if re-biopsy is impossible or refused by the subject, his/her eligibility for enrollment shall be confirmed by both the investigator and the sponsor.
✓. Patients with primary malignant brain tumors that are asymptomatic, or that are symptomatic but on a stable or decreasing dose of steroids for at least 2 weeks are eligible for enrollment. The specific criteria are as follows:Subjects with inactive and asymptomatic primary malignant brain tumors;Subjects who have active, mild neurological signs and symptoms currently requiring no therapy with steroids, and have no history of epileptic seizure within 2 weeks prior to initiation of treatment;Subjects who have active, neurological signs and symptoms and were on a stable or gradually reducing dose up to 5 mg of dexamethasone (or equivalent) per day within 2 weeks prior to initiation of treatment;
What they're measuring
1
MTD
Timeframe: From the enrollment of subjects to the end of Cycle 1 (each cycle is 28 days) or up to treatment discontinuation, whichever occurs first, assessed up to 28 days.
2
Recommended Phase 2 Dose(PR2D)
Timeframe: From the enrollment of subjects to the end of Cycle 1 (each cycle is 28 days) or up to treatment discontinuation, whichever occurs first, assessed up to 28 days.
3
Dose Limiting Toxicity(DLT)
Timeframe: cycle 1（28 days）
4
The incidence of treatment-related adverse events AE(s)
Timeframe: Up to 28 days from treatment discontinuation
5
Number of participants with abnormal laboratory values
Timeframe: Up to 28 days from treatment discontinuation
6
Number of participants with abnormal vital signs
Timeframe: Up to 28 days from treatment discontinuation
7
Number of participants with abnormal physical examinations
Timeframe: Up to 28 days from treatment discontinuation
✓. Antitumor efficacy was evaluated using the RANO criteria, which required the presence of at least one measurable lesion (the diameters that are perpendicular to each other are not less than 10 mm). Lesions previously treated with radiotherapy shall not be deemed as target lesions unless significant progression as shown on imaging.
✓. Karnofsky PS score of ≥ 60.
✓. Survival expectancy ≥ 3 months.
Exclusion criteria
✕. Women who are pregnant or breast-feeding.
✕. Subjects with history of neoplasm malignant (except for primary malignant brain tumors) within 5 years prior to screening, excluding cured carcinoma in situ of cervix, non-melanoma skin cancer, localized prostate cancer and other tumors/cancers that have undergone radical treatment and shown no signs of disease for at least 3 years (This exclusion criterion is only applicable for dose expansion stage). For the dose escalation stage, any patient with double primary malignant solid tumors who can indeed benefit from this study as confirmed by the investigator is eligible for the screening.
✕. Subjects with intracranial hypertension or associated risks (e.g., intracranial infection, intracranial hemorrhage) to be controlled.
✕. Subjects with clinically uncontrolled pleural effusion, pericardial effusion, or ascites who, in the judgement of the investigator, are not eligible for enrollment.
✕. Subjects with history of symptomatic stroke within 6 months prior to initiation of study treatment.
✕. Subjects with epileptic seizure within 14 days prior to initiation of study treatment.
✕. Impaired cardiac function or clinically significant cardiovascular disorder, including but not limited to any of the following:Left Ventricular Ejection Fraction (LVEF) \< 50% as determined via cardiac ultrasound.Long QT syndrome congenital.QTcF (as corrected via Fridericia formula) ≥ 450 ms at screening.Second-degree type II AV block or third-degree AV block.Unstable angina pectoris within 6 months prior to starting study drug.Acute myocardial infarction within 6 months prior to starting study drug.New York Heart Association (NYHA) Class II or higher heart failure within 6 months prior to study treatment.Ventricular arrhythmias \> Grade 2 within 6 months prior to study treatment.Poorly controlled hypertension as defined as systolic blood pressure of \>160 mmHg or diastolic blood pressure of \> 100 mmHg despite use of antihypertensive medications.Combined with any pulmonary embolism, or presence of any serious deep vein thrombosis on lower extremities that require medical interventions such as vena cava filter insertion at the screening.
✕. Poorly controlled diabetes (fasting glucose \> 10 mmol/L or Glycosylated Haemoglobin (HbA1c) \> 8%) despite standard drug therapy.
Number of participants with abnormal ophthalmic evaluation
Timeframe: Up to 28 days from treatment discontinuation
9
Number of participants with abnormal ECG
Timeframe: Up to 28 days from treatment discontinuation
10
Number of participants with abnormal Karnofsky PS
Timeframe: Up to 28 days from treatment discontinuation