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Clinical Trial 20956

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

Phase: Phase I
Prinicipal Investigator: Peter Forsyth

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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

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. 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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