Trial Title:
A Study of ABM-1310 in Patients With BRAF V600-Mutant Relapsed and Drug Resistant Primary Malignant Brain Tumors
NCT ID:
NCT05892653
Condition:
Primary Malignant Brain Tumor
Conditions: Official terms:
Brain Neoplasms
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
ABM-1310
Description:
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.
Arm group label:
Dose Escalation and Dose Expansion
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Subjects who are able to understand and voluntarily sign informed consent forms
(ICFs).
2. Male and female subjects at the age of ≥18 at the time of screening.
3. 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.
4. 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.
5. 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;
6. 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.
7. Karnofsky PS score of ≥ 60.
8. Survival expectancy ≥ 3 months.
9. Adequate organ function (no blood transfusion and no use of granulocyte
colony-stimulating factor, or other hematopoietic stimulator support within 2 weeks
before the first administration of the study drug) confirmed as evidenced
by:Absolute Neutrophil Count (ANC) ≥ 1.5×10^9/L;Hemoglobin (Hgb) ≥ 90 g/dl;Platelets
(Plt) ≥ 75×10^9/L;AST/ALT ≤ 2.5 x ULN or ≤ 5.0 x ULN if liver metastases are
present;Bilirubin total ≤ 1.5 x ULN, or bilirubin direct < ULN for patients with
bilirubin total levels >1.5 ULN;Serum creatinine < 1.5 x ULN or creatinine clearance
> 50 mL/min (as calculated via Cockcroft-Gault formula based on the actual body
weight of the subject;International normalized ratio (INR) and activated partial
thromboplastin time (APTT) ≤ 1.5 x ULN for subjects not receiving anticoagulant
therapy, and INR is maintained within the standard range of treatment prior to
starting study drug for subjects receiving anticoagulant therapy.
10. Hepatitis B virus surface antigen (HBsAg) is negative, or HBsAg is positive but HBV
DNA titer is below the lower limit of positive detection of the participating site
at screening.HBsAg-positive or HBV-DNA positive subjects shall be managed according
to institutional guidelines (anti-HBV therapy, where appropriate, and close
monitoring of liver function and HBV-DNA replication shall be performed).
11. Negative hepatitis C virus (HCV) antibody test or positive HCV antibody test at the
time of screening followed by a negative HCV-RNA test result.HCV-RNA testing is
performed only for subjects with a positive HCV antibody test result.
12. Negative HIV test result at the time of screening.
13. All pre-menopausal women and women with menolipsis < 12 months should have a
negative pregnancy test result within 7 days before starting study treatment.
14. Must agree to take sufficient contraceptive methods before initiation of study
treatment, during the study, and for at least 3 months after the last dose of the
study drug.
15. Subjects who are able to swallow a capsule in whole (without chewing, crushing, or
opening).
Exclusion Criteria:
1. Women who are pregnant or breast-feeding.
2. 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.
3. Subjects with intracranial hypertension or associated risks (e.g., intracranial
infection, intracranial hemorrhage) to be controlled.
4. Subjects with clinically uncontrolled pleural effusion, pericardial effusion, or
ascites who, in the judgement of the investigator, are not eligible for enrollment.
5. Subjects with history of symptomatic stroke within 6 months prior to initiation of
study treatment.
6. Subjects with epileptic seizure within 14 days prior to initiation of study
treatment.
7. 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.
8. Poorly controlled diabetes (fasting glucose > 10 mmol/L or Glycosylated Haemoglobin
(HbA1c) > 8%) despite standard drug therapy.
9. Subjects with:CTCAE grade 2 or higher unresolved diarrhea, or Impaired
gastrointestinal (GI) function or GI diseases that may significantly alter the
absorption of ABM-1310 (e.g., ulcerative diseases, uncontrolled nausea, vomiting,
diarrhea, malabsorption syndrome, or small bowel resection)
10. Previous or current, Grade 2 or higher eye disorder, such as retinal vein occlusion
(RVO).
11. Severe chronic or active infections requiring intravenous anti-infective therapy
within 2 weeks prior to study treatment, including but not limited infectious
complications leading to hospitalization, bacteremia, severe pneumonia, or active
tuberculosis.Subjects with local fungal infections of skin or nails are allowed for
enrollment. Subjects receiving prophylactic antibiotics (e.g., to prevent urinary
tract infections or exacerbations of chronic obstructive pulmonary disease) are
eligible for study (except for antibiotics prohibited by the protocol).
12. Subjects with solid organ or hematopoietic stem cell transplant within the past 5
years.
13. Patients receiving chemotherapy, targeted therapy, or immunotherapy within 4 weeks
prior to study treatment, including the followings:Receiving nitrosourea or
mitomycin-C within 6 weeks prior to study treatment.Receiving fluorouracil or small
molecule targeted drug therapy within 5 half-lives or 2 weeks (whichever is longer)
prior to study treatment.Receiving Chinese herbal or patent medicine within 2 weeks
prior to study treatment for anti-tumor indications.
14. Patients receiving radiotherapy to head within 4 weeks prior to study treatment.
15. Adverse reactions resulted from prior antitumor therapy that have not resolved to
baseline or ≤ grade 1 (CTCAE 5.0) , except alopecia or ≤ grade 2 peripheral
neuropathy, hypothyroidism stabilized by hormone replacement therapy, etc.
16. Subjects who have undergone major surgery within 4 weeks prior to study treatment or
who have not recovered from side effects of such therapy or who are expected to
undergo major surgery during study treatment. However, a minimum of 2 weeks recovery
time from major surgery to starting study drug is required if in investigator's
opinion the patient has recovered from such major surgery.
17. Subjects currently receiving therapeutic doses of warfarin sodium or any other
coumarin-derivative anticoagulants.
18. Subjects who are currently receiving treatment with medication that has a known risk
to prolong the QT interval and cannot either be discontinued or switched to a
different medication prior to starting study drug.
19. Known, documented or suspected history of drug abuse, expect opioids prescribed for
pain relief, etc.
20. Past or current evidence of any condition, therapy, or laboratory abnormality that,
in the opinion of the investigator, might affect the results of the study, and
interfere with the subject's participation and study compliance.
21. Other severe and/or uncontrolled concomitant diseases that could cause unacceptable
safety risks or compromise compliance with the study protocol.
22. Other conditions that, in the judgement of the investigator, are inappropriate for
enrollment in the study.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Beijing Tiantan Hospital Affiliated to Capital Medical University
Address:
City:
Beijing
Zip:
100070
Country:
China
Status:
Recruiting
Contact:
Last name:
Wenbin Li
Phone:
15301377998
Email:
neure55@126.com
Investigator:
Last name:
Wenbin Li
Email:
Principal Investigator
Facility:
Name:
Shenzhen Second People's Hospital
Address:
City:
Shenzhen
Zip:
518020
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Guodong Huang
Phone:
13590119456
Email:
jxgd211@163.com
Investigator:
Last name:
Guodong Huang
Email:
Principal Investigator
Facility:
Name:
First affiliated hospital to SuZhou University
Address:
City:
Suzhou
Zip:
215006
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Gang Chen
Phone:
13771908806
Email:
nju_neurosurgery@163.com
Investigator:
Last name:
Gang Chen
Email:
Principal Investigator
Facility:
Name:
Huashan Hospital Affiliated to Fudan University
Address:
City:
Shanghai
Zip:
200040
Country:
China
Status:
Recruiting
Contact:
Last name:
Mao Ying, Dr
Phone:
021-52889999
Email:
maoying@fudan.edu.cn
Facility:
Name:
The Second Affiliated Hospital of the Chinese People's Liberation Army Air Force Military Medical University
Address:
City:
Xi'an
Zip:
710038
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Yan Qu
Phone:
18629074363
Email:
yanqu0123@icloud.com
Investigator:
Last name:
Qu Yan
Email:
Principal Investigator
Start date:
June 30, 2023
Completion date:
May 29, 2028
Lead sponsor:
Agency:
ABM Therapeutics Shanghai Company Limited
Agency class:
Industry
Source:
ABM Therapeutics Shanghai Company Limited
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05892653
