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
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.
Phase 1a Primary:
To assess the safety and tolerability of PF-07284890 at increasing dose levels, to estimate the MTD, and to select the recommended dose for further study, as both
a single agent and in combination with binimetinib
Phase 1a Secondary:
To characterize the single- and multiple-dose PK of PF-07284890 as a single agent and in combination with binimetinib and of binimetinib in combination with PF-07284890.
To evaluate preliminary clinical activity of PF-07284890 as a single agent and in combination with binimetinib.
Phase 1b Primary:
To evaluate anti-tumor efficacy of PF-07284890 at the recommended dose for further study in combination with binimetinib
Phase 1b Secondary:
To confirm the safety and tolerability of PF-07284890 at the recommended dose for further study in combination with binimetinib.
To evaluate single- and multiple-dose PK profiles of PF-07284890 at the recommended dose for further study in combination with binimetinib and of binimetinib in combination with PF-07284890.
To assess additional measures of anti-tumor efficacy of PF-07284890 at the recommended dose for further study in combination with binimetinib.
To evaluate the effect of repeated administration of PF-07284890 in combination with binimetinib on single dose PK of midazolam (Cohort 6 only).
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 or NSCLC 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 is permitted; with or without disease in the brain as long as it does not meet requirements for Cohort 1-4; with or without prior BRAF and/or MEK inhibitor; asymptomatic or symptomatic in the brain as defined above. For patients with primary brain tumors, RANO should be used to determine baseline brain lesion status and response assessment during the study.
Cohort 6 (DDI Sub-study): 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
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