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

C4471001

First-in-human study to assess safety, tolerability, PK, and preliminary activity of PF-07284890 as a single agent and in combination with binimetinib in participants with BRAF V600-mutated advanced solid tumor malignancies with and without brain involvement.

2021-01-08

2024-03-20

2024-03-20

Terminated

Early phase I

65

Inclusion Criteria: * Age ≥16 years at the time of consent * Histologically confirmed diagnosis of advanced/metastatic solid tumor including primary brain tumor * Documented evidence of a BRAF V600 mutation in tumor tissue or blood * Confirmation of availability of adequate tumor tissue for submission to the sponsor/central laboratory * Presence or absence of brain involvement unless specified below * Dose Expansion (Part B) * Cohort 1, 2, 3, 4: melanoma with at least 1 parenchymal brain lesion * Cohort 1,3: asymptomatic in the brain for at least 14 days prior to start of study treatment * Cohort 2,4: symptomatic in the brain within 14 days prior to the start of study treatment * Cohort 5: any solid tumor that does not meet requirements for Cohorts 1-4, history of or current leptomeningeal metastases. * Optional Cohort 6 (DDI Sub-study) and 7 (Food-Effect): if brain involvement present, must be asymptomatic * Disease progression despite prior treatment and no acceptable alternative treatment options available unless specified below * Dose Expansion (Part B) * Cohort 1, 2: No prior BRAF inhibitor in the metastatic setting or in the adjuvant setting within 6 months of study treatment * Cohort 3, 4: Required prior BRAF inhibitor in the metastatic setting or in the adjuvant setting within 6 months of treatment * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 Exclusion Criteria: * Brain metastasis/primary brain tumor requiring immediate local intervention * History of or current leptomeningeal metastases * Any other active malignancy within 2 years prior to enrollment * Radiation therapy to visceral metastases within 14 days prior to study treatment. WBRT within 28 days prior to study treatment. * Systemic anti-cancer therapy or small-molecular therapeutic(s) within 2 weeks prior to start of study treatment; Antibody based agents within 4 weeks prior to start of study treatment. * History or current evidence of RVO or current risk factors for RVO; History of retinal degenerative disease

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'SEQUENTIAL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 65, 'type': 'ACTUAL'}}

2024-04-03