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Clinical Trial 20956

Cancer Type: Multiple
Study Type: Treatment
NCT#: NCT04543188

Phase: Phase I
Principal Investigator: Forsyth, Peter

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Overview

Study Title

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

Summary

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.

Objective

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).

Treatments

Therapies

Chemotherapy (NOS); Therapy (NOS)

Medications

Binimetinib (); Midazolam (); PF-07284890 ()

Inclusion Criteria

Inclusion Criteria:

  • Age 18 years or more 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 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

  • Exclusion Criteria

    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
  • Other exclusions may apply

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