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

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 braintumor 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 ortreating physician, or (d) intolerance to standard treatment. Subjects who werepreviously treated with BRAF and/or MEK inhibitors are allowed to be enrolled inthis study.

4. Documentation of positive BRAF V600 mutation is required for enrollment. It isrecommended to provide sufficient fresh/archived tumor tissue samples (formalin-fixed paraffin-embedded tumor specimens [preferred]) or 5-10 availableunstained sections of good quality for verification of BRAF V600 mutation status atthe central laboratory. For any subject who is unable to provide suitable andadequate tumor specimens, re-biopsy (with controllable safety) can be performed in anon-mandatory manner if it is feasible as assessed by the investigator and thesubject gives informed consent; if re-biopsy is impossible or refused by thesubject, his/her eligibility for enrollment shall be confirmed by both theinvestigator and the sponsor.

5. Patients with primary malignant brain tumors that are asymptomatic, or that aresymptomatic but on a stable or decreasing dose of steroids for at least 2 weeks areeligible for enrollment. The specific criteria are as follows:Subjects with inactiveand asymptomatic primary malignant brain tumors;Subjects who have active, mildneurological signs and symptoms currently requiring no therapy with steroids, andhave no history of epileptic seizure within 2 weeks prior to initiation oftreatment;Subjects who have active, neurological signs and symptoms and were on astable or gradually reducing dose up to 5 mg of dexamethasone (or equivalent) perday within 2 weeks prior to initiation of treatment;

6. Antitumor efficacy was evaluated using the RANO criteria, which required thepresence of at least one measurable lesion (the diameters that are perpendicular toeach other are not less than 10 mm). Lesions previously treated with radiotherapyshall not be deemed as target lesions unless significant progression as shown onimaging.

7. Karnofsky PS score of ≥ 60.

8. Survival expectancy ≥ 3 months.

9. Adequate organ function (no blood transfusion and no use of granulocytecolony-stimulating factor, or other hematopoietic stimulator support within 2 weeksbefore the first administration of the study drug) confirmed as evidencedby: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 arepresent;Bilirubin total ≤ 1.5 x ULN, or bilirubin direct < ULN for patients withbilirubin 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 bodyweight of the subject;International normalized ratio (INR) and activated partialthromboplastin time (APTT) ≤ 1.5 x ULN for subjects not receiving anticoagulanttherapy, and INR is maintained within the standard range of treatment prior tostarting study drug for subjects receiving anticoagulant therapy.

10. Hepatitis B virus surface antigen (HBsAg) is negative, or HBsAg is positive but HBVDNA titer is below the lower limit of positive detection of the participating siteat screening.HBsAg-positive or HBV-DNA positive subjects shall be managed accordingto institutional guidelines (anti-HBV therapy, where appropriate, and closemonitoring of liver function and HBV-DNA replication shall be performed).

11. Negative hepatitis C virus (HCV) antibody test or positive HCV antibody test at thetime of screening followed by a negative HCV-RNA test result.HCV-RNA testing isperformed 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 anegative pregnancy test result within 7 days before starting study treatment.

14. Must agree to take sufficient contraceptive methods before initiation of studytreatment, during the study, and for at least 3 months after the last dose of thestudy drug.

15. Subjects who are able to swallow a capsule in whole (without chewing, crushing, oropening).

Exclusion Criteria:

1. Women who are pregnant or breast-feeding.

2. Subjects with history of neoplasm malignant (except for primary malignant braintumors) within 5 years prior to screening, excluding cured carcinoma in situ ofcervix, non-melanoma skin cancer, localized prostate cancer and other tumors/cancersthat have undergone radical treatment and shown no signs of disease for at least 3years (This exclusion criterion is only applicable for dose expansion stage). Forthe dose escalation stage, any patient with double primary malignant solid tumorswho can indeed benefit from this study as confirmed by the investigator is eligiblefor the screening.

3. Subjects with intracranial hypertension or associated risks (e.g., intracranialinfection, intracranial hemorrhage) to be controlled.

4. Subjects with clinically uncontrolled pleural effusion, pericardial effusion, orascites 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 ofstudy treatment.

6. Subjects with epileptic seizure within 14 days prior to initiation of studytreatment.

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 AVblock or third-degree AV block.Unstable angina pectoris within 6 months prior tostarting study drug.Acute myocardial infarction within 6 months prior to startingstudy 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 monthsprior to study treatment.Poorly controlled hypertension as defined as systolic bloodpressure of >160 mmHg or diastolic blood pressure of > 100 mmHg despite use ofantihypertensive medications.Combined with any pulmonary embolism, or presence ofany serious deep vein thrombosis on lower extremities that require medicalinterventions 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 Impairedgastrointestinal (GI) function or GI diseases that may significantly alter theabsorption 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 therapywithin 2 weeks prior to study treatment, including but not limited infectiouscomplications leading to hospitalization, bacteremia, severe pneumonia, or activetuberculosis.Subjects with local fungal infections of skin or nails are allowed forenrollment. Subjects receiving prophylactic antibiotics (e.g., to prevent urinarytract infections or exacerbations of chronic obstructive pulmonary disease) areeligible for study (except for antibiotics prohibited by the protocol).

12. Subjects with solid organ or hematopoietic stem cell transplant within the past 5years.

13. Patients receiving chemotherapy, targeted therapy, or immunotherapy within 4 weeksprior to study treatment, including the followings:Receiving nitrosourea ormitomycin-C within 6 weeks prior to study treatment.Receiving fluorouracil or smallmolecule 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 weeksprior 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 tobaseline or ≤ grade 1 (CTCAE 5.0) , except alopecia or ≤ grade 2 peripheralneuropathy, hypothyroidism stabilized by hormone replacement therapy, etc.

16. Subjects who have undergone major surgery within 4 weeks prior to study treatment orwho have not recovered from side effects of such therapy or who are expected toundergo major surgery during study treatment. However, a minimum of 2 weeks recoverytime from major surgery to starting study drug is required if in investigator'sopinion the patient has recovered from such major surgery.

17. Subjects currently receiving therapeutic doses of warfarin sodium or any othercoumarin-derivative anticoagulants.

18. Subjects who are currently receiving treatment with medication that has a known riskto prolong the QT interval and cannot either be discontinued or switched to adifferent medication prior to starting study drug.

19. Known, documented or suspected history of drug abuse, expect opioids prescribed forpain 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, andinterfere with the subject's participation and study compliance.

21. Other severe and/or uncontrolled concomitant diseases that could cause unacceptablesafety risks or compromise compliance with the study protocol.

22. Other conditions that, in the judgement of the investigator, are inappropriate forenrollment in the study.