Binimetinib in Patients With BRAF Fusion-positive Low-grade Glioma or Pancreatic Cancer (Perfume)

Inclusion Criteria: Inclusion criteria for both cohort A and B

1. BRAF fusion or rearrangement is detected by reimbursed NGS-based cancer gene paneltests, cancer gene panel tests performed under advanced medical treatment, or clinicalstudy (including liquid biopsy).
2. Unresectable or recurrent
3. No symptomatic brain metastasis, carcinomatous meningitis or spinal metastasisrequiring surgical intervention or radiotherapy
4. No cardiac effusion, pleural effusion, or ascites requiring treatment
5. Not received anti-cancer drug within 14 days before registration, nor received otherstudy drug (molecular targeting drug, immune therapy) within 21 days beforeregistration
6. Not received operation under general anesthesia within 28 days before registration
7. Not received radiation therapy (including gamma knife, cyber knife) within 14 daysbefore registration
8. Left ventricular ejection fraction >= 50% by echocardiography or MUGA (multigatedacquisition scan) within 28 days before registration
9. Having all laboratory tests performed within 14 days before registration and thevalues are within the following range. Patients should not receive administration ofG-CSF and/or blood transfusion within 14 days before the blood collection (1) Absoluteneutrophil count >= 1.500/mm3 (2) Platelet count >= 10.0 X 10(4))/mm3 (3) Hemoglobin >= 8.0 g/dL (4) Total bilirubin <= 1.5 g/dL (5) Aspartate aminotransferase (AST) <= 100 U/L (6) Alanine aminotransferase (ALT) <= 100 U/L (7) Serum creatinine <= 1.5mg/dL
10. Patients who are able to swallow orally administered medication.
11. Consent to at least 30 days of contraception and limited egg donation (including eggretrieval for future egg transfer) after last administration of study drug forchild-bearing status women. Consent to 90 days of contraception and limited spermdonation after last administration of study drug for men.
12. Written informed consent (When registering patient under 18, a signed consent formmust be obtained from both the patient and the parent or legal guardian.) Cohort A
13. Histopathologically diagnosed as low-grade glioma, based on WHO classification of 2007, 2016 and 2021. The grade is WHO grade 1 or 2.
14. Age at the time of registration is 12 years or older (When registering a patient under 18, a signed consent form must be obtained from both the patient and the parent orlegal guardian), and patients who are 12-17 years old have to be 40 kg or over in bodyweight. There is no limitation in body weight for patients who are 18 years or older.
15. Lansky Performance Status (LPS) >= 70 for patients 12-15 years old KarnofskyPerformance Status (KPS) >= 70 for patients 16 years or older
16. Having measurable disease within 28 days before registration
17. Patients suffice the following. (1) Having adequate initial treatment depending on theprimary central nervous tumor including surgery if recommended treatment is available. (2) Neurologically stable.

(3) Multiple lesion or dissemination is not detected with MRI at the registration. 18) Not increased steroid for low-grade glioma within 14 days before registration and thedosage of steroid in equivalent to 50 mg prednisolone or less. Cohort B 19) Histopathologically diagnosed as pancreatic cancer (histologically notspecified). 20) Having progression after at least one regimen of chemotherapy excluding adjuvanttherapy. 21) Age at the time of registration is 18 years or older. 22) Performance Status (ECOG) is 0 or 1 23) Having measurable disease within 28 days before registration detected byenhanced CT (Head, chest, abdominal, pelvic: under 5 mm in slice)

Exclusion Criteria:

1. Active double primary cancer (but not [1]-[3]): [1] completely resected followingcancers: basal cell carcinoma, stage I squamous cell carcinoma, carcinoma in situ,intramucosal carcinoma, superficial bladder cancer, [2] gastrointestinal cancercuratively resected with ESD or EMR, and [3] other cancers with no recurrence for morethan 5 years.
2. Patients with symptomatic congestive heart failure of NYHA class II-IV or arrythmia (over grade 2) occurring in less than 6 months before registration.
3. Patients with myocardial infarction or unstable angina occurring in less than 6 monthsbefore registration.
4. Patients with corrected QT interval (QTcF) > 480 ms in ECG performed within 14 daysbefore enrollment.
5. Patients with infections requiring systemic treatment.
6. Patients with uncontrolled hypertension (systolic blood pressure: over 150 mmHg ordiastolic blood pressure: over 100 mmHg).
7. Patients with history or findings of retinal vein occlusion (RVO) or having RVO riskfactor (unstable glaucoma, ocular hypertension, hyperviscosity syndrome,hypercoagulability syndrome, etc.)
8. Patients with history or complication of retinal degenerative disease other than RVO (central serous chorioretinopathy, retinal detachment, age-related maculardegeneration, etc.)
9. Patients with uncontrolled diabetes mellitis.
10. Patients with venous thrombus (transient ischemic attack, stroke, massive deep veinthrombosis, pulmonary embolism, etc.) occurring in less than 3 months
11. Patients who have neuromuscular disease with CK elevation (inflammatory myopathy,muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy, etc.).
12. Prior treatment with MEK inhibitors.
13. Previous severe hypersensitive reaction to ingredient including binimetinib.
14. Patients who are positive for either HIV antibody, HBs antigen, or HCV-RNA.
15. Negative for HBs antigen, positive for HBs antibody or HBc antibody, and positive forHBV-DNA assay. (If it is less than or equal to the detection sensitivity, patients arenot excluded)
16. Patients with concomitant diseases that affect gastrointestinal function.
17. Women who are pregnant, breastfeeding and need to continue breastfeeding in thefuture, and women who may be pregnant.
18. Patients with psychiatric diseases or psychological symptoms interfering withparticipation in the trial.
19. Patients who are deemed inappropriate for participation in the trial by the principalinvestigator or sub-investigator.