A Study of ABM-1310 in Patients With BRAF V600-Mutant Advanced Solid Tumors

Exclusion Criteria

• •7. ECOG score of 0 or 1 or Karnofsky PS score of ≥ 70.
• •8. Life 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.
• •o 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.
• •o 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).
• •1. Women who are pregnant or breast-feeding.
• •2. Subjects with history of neoplasm malignant 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; however, those with any combined primary hematological malignant tumor shall be excluded).
• •3. Subjects with intracranial hypertension or associated risks (e.g., intracranial infection, intracranial hemorrhage).
• •5. Subjects with cancerous meningitis (leptomeningeal disease \[LMD\]).
• •6. Subjects with history of symptomatic stroke within 6 months prior to initiation of study treatment.
• •7. Subjects with epileptic seizure within 14 days prior to initiation of study treatment.
• •8. 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 (males) or 470 ms (females) 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 .
• •9. Poorly controlled diabetes (fasting glucose \> 10 mmol/L or Glycosylated Haemoglobin (HbA1c) \> 8%) despite standard drug therapy.
• •10. 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)
• •11. Previous or current, Grade 2 or higher eye disorder, such as retinal vein occlusion (RVO).
• •12. 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.
• •o 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).
• •13. Subjects with solid organ or hematopoietic stem cell transplant within the past 5 years.
• •14. 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.
• •15. Subjects receiving radical radiotherapy or radiotherapy to more than 30% of bone marrow or whole-brain radiotherapy (WBRT) within 4 weeks or palliative radiotherapy for non-target lesions with the aim of relieving symptoms (e.g., bone radiotherapy for pain relief) or stereotactic radiosurgery (including SRS) within 2 weeks prior to starting study drug.
• •16. 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.
• •17. 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.
• •18. Subjects currently receiving therapeutic doses of warfarin sodium or any other coumarin-derivative anticoagulants.