A TWO-PART, PHASE 1A/B, OPEN-LABEL, MULTICENTER TRIAL EVALUATING PHARMACOKINETICS, SAFETY AND EFFICACY OF PF 07284890 (ARRY 461) IN PARTICIPANTS WITH BRAF V600 MUTANT SOLID TUMORS WITH AND WITHOUT BRAIN INVOLVEMENT

Number of Participants With Dose Limiting Toxicities (DLTs): Phase 1a

时间窗: Cycle 1 (21 Days)

DLT was defined as any adverse event (AE) or abnormal laboratory value which were related to study treatment and assessed as unrelated to disease (disease progression), occurring during the first 21 days of treatment that met at least 1 of the study specified criteria. DLTs were graded according to the National Cancer Institute- Common Terminology Criteria for Adverse Events (NCI-CTCAE), version (v) 5.0.

Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Serious Treatment Related TEAEs, Grade 3 or 4 TEAEs and Grade 5 TEAEs by NCI CTCAE v5.0: Phase 1a

时间窗: From first dose of study treatment (Day 1) up to 30 days post last dose of study treatment or start of new anti-cancer therapy (-1 Day) whichever occurred first (maximum treatment exposure: 542 days; maximum follow-up: 572 days)

An adverse event (AE) was any untoward medical occurrence in participant/ clinical study participant temporally associated with use of study intervention, whether/ not considered related to study intervention. TEAEs were defined as any AE that occurs during on-treatment period. The on-treatment period was defined as period that starts with first dose of study treatment and ends at last dose of study treatment +30 days, or start of new anti-cancer therapy \[- 1 day\], whichever occurred first. Serious TEAEs were any untoward medical occurrence at any dose that: suspected to cause death; life-threatening; required hospitalization; persistent/significant disability/incapacity and might caused congenital anomaly/birth defect. Serious treatment related TEAEs were related to study treatment and relatedness was judged by investigator. TEAEs were graded according to NCI-CTCAE v 5.0 (grade 3= severe, grade 4= life-threatening and grade 5= death related to AE). AEs included SAEs and all non-SAE.

Number of Participants With Hematology Laboratory Abnormalities of Any CTCAE Grade: Phase 1a

时间窗: From first dose of study treatment (Day 1) up to 30 days post last dose of study treatment (maximum treatment exposure: 542 days; maximum follow-up: 572 days)

The following hematology laboratory parameters were assessed: activated partial thromboplastin time prolonged, anemia, hemoglobin increased, international normalized ratio (INR) increased, leukocytosis, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased and white blood cell decreased. Laboratory abnormality events were graded according to NCI CTCAE v5.0; grade 1=mild, grade 2=moderate, grade 3=severe, grade 4=life-threatening consequences and grade 5=death. In this outcome measure, those number of participants are reported who had hematology laboratory abnormality in any parameter of any CTCAE Grades.

Number of Participants With Chemistry Laboratory Abnormalities of Any CTCAE Grade: Phase 1a

时间窗: From first dose of study treatment (Day 1) up to 30 days post last dose of study treatment (maximum treatment exposure: 542 days; maximum follow-up: 572 days)

The following chemistry laboratory parameters were assessed: alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, creatine phosphokinase (CPK) increased, creatinine increased, hypercalcemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia and hyponatremia. Laboratory abnormality events were graded according to NCI CTCAE v5.0; grade 1=mild, grade 2=moderate, grade 3=severe, grade 4=life-threatening consequences and grade 5=death. In this outcome measure, those number of participants are reported who had chemistry laboratory abnormality in any parameter of any CTCAE Grades.

Number of Participants With Dose Interruptions Due to TEAEs: Phase 1a

时间窗: During study treatment (from first dose of study treatment [Day 1] up to last dose of study treatment [maximum treatment exposure: 542 days])

Dose interruption was defined as a planned dosing day with 0 mg total dose administered. Dose interruptions were applicable to unexpected dose interruptions. In this outcome measure, dose interruptions for any drug were considered.

Number of Participants With Dose Reduction Due to TEAEs: Phase 1a

时间窗: During study treatment (from first dose of study treatment [Day 1] up to last dose of study treatment [maximum treatment exposure: 542 days])

A dose reduction was defined as the day when the actual dose was less than the planned dose at enrollment and the actual dose was greater than 0 mg (ie, missed doses were not counted as a reduction). In this outcome measure, dose reductions for any drug were considered.

Number of Participants With Dose Discontinuations Due to TEAEs: Phase 1a

时间窗: During study treatment (from first dose of study treatment [Day 1] up to last dose of study treatment [maximum treatment exposure: 542 days])

In this outcome measure, dose discontinuations for any drug due to TEAEs were considered.

Extracranial Response Rate by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1: Phase 1b

时间窗: From date of first dose until CR or PR (maximum treatment exposure: 400 days)

Extracranial response rate was defined as the percentage of participants with a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) in extracranial lesions by Investigator assessment per RECIST v1.1. CR: disappearance of all target and non-target lesions. Any pathological lymph nodes (non-target) must have reduction in short axis to less than (\<) 10 millimeter (mm). PR: at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Intracranial Response Rate by mRECISTv1.1: Phase 1b

时间窗: From date of first dose until CR or PR (maximum treatment exposure: 400 days)

Intracranial response rate as assessed using modified RECIST (mRECIST) v 1.1., was defined as the percentage of participants with brain or central nervous system (CNS) involvement who achieved a CR or PR. CR: disappearance of all target and non-target lesions. For target lesions: Any pathological lymph nodes must be \<10 mm in the short axis. For non-target lesions: All lymph nodes identified as a site of disease at baseline must be non-pathological (eg, \<10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Overall Response Rate (ORR): Phase 1b

时间窗: From date of first dose until CR or PR (maximum treatment exposure: 400 days)

ORR: percentage of participants with BOR of confirmed CR/PR by investigator assessment in intracranial metastasis (mRECISTv1.1) and extracranial lesions (RECISTv1.1). RECIST v1.1- CR: disappearance of all target and non-target lesions. Any pathological lymph node (non-target) must have reduction in short axis to \<10mm. PR: at least 30% decrease in sum of diameters of target lesions, taking as reference baseline sum diameters. mRECIST- CR: disappearance of all target and non-target lesion. For target lesion: Any pathological lymph nodes must be \<10 mm in short axis. For non-target lesion: All lymph nodes identified as site of disease at baseline must be non-pathological (eg, \<10 mm short axis). PR: at least 30% decrease in sum of diameters of target lesions, taking as reference baseline sum diameters.

Response Rate Using Response Assessment in Neuro-Oncology (RANO) for Primary Brain Tumors: Phase 1b

时间窗: From date of first dose until CR or PR (maximum treatment exposure: 400 days)

RANO response rate was defined as the percentage of glioblastoma participants who achieved a CR or PR per RANO. CR was defined as complete disappearance of all enhancing measurable and non-measurable disease sustained for more than or equal to (\>=) 4 weeks; no new lesions; stable or improved non-enhancing (T2/ \[fluid attenuated inversion recovery\] FLAIR) lesions; off steroids and neurological condition stable or improved. PR was defined as \>=50% decrease compared to baseline in the sum of the perpendicular diameters of all measurable enhancing lesions sustained for at least 4 weeks; no progression of non-measurable disease; no new lesions; stable or improved non enhancing (T2/FLAIR) lesions on the same or lower dose of corticosteroids compared with baseline scan; the corticosteroid dose at the time of the scan evaluation should be no greater than the dose at the time of the baseline scan and neurological condition stable or improved.