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Purpose

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.

Conditions

Eligibility

Eligible Ages
Over 16 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
PF-07284890 (Part A monotherapy) 		Monotherapy dose escalation of PF-07284890
  • Drug: PF-07284890
    PF-07284890 will be administered orally, daily for 21 consecutive days (21-day cycle)
    Other names:
    • ARRY-461
Experimental
PF-07284890+binimetinib (Part A combo-therapy) 		Combination dose escalation of PF-07284890 + binimetinib
  • Drug: PF-07284890
    PF-07284890 will be administered orally, daily for 21 consecutive days (21-day cycle)
    Other names:
    • ARRY-461
  • Drug: Binimetinib
    Binimetinib will be administered together with PF-07284890 orally, 45mg twice daily
    Other names:
    • Mektovi
Experimental
Expansion Phase (Part B, Cohort 1) 		PF-07284890 (at recommended dose from Part A) plus binimetinib in participants with BRAF V600 melanoma, with asymptomatic brain involvement, and no prior BRAF or MEK inhibitor utilization
  • Drug: PF-07284890
    PF-07284890 will be administered orally, daily for 21 consecutive days (21-day cycle)
    Other names:
    • ARRY-461
  • Drug: Binimetinib
    Binimetinib will be administered together with PF-07284890 orally, 45mg twice daily
    Other names:
    • Mektovi
Experimental
Expansion Phase (Part B, Cohort 2) 		PF-07284890 (at recommended dose from Part A) plus binimetinib in participants with BRAF V600 melanoma, with symptomatic brain involvement, and no prior BRAF or MEK inhibitor utilization
  • Drug: PF-07284890
    PF-07284890 will be administered orally, daily for 21 consecutive days (21-day cycle)
    Other names:
    • ARRY-461
  • Drug: Binimetinib
    Binimetinib will be administered together with PF-07284890 orally, 45mg twice daily
    Other names:
    • Mektovi
Experimental
Expansion Phase (Part B, Cohort 3) 		PF-07284890 (at recommended dose from Part A) plus binimetinib in participants with BRAF V600 melanoma, with asymptomatic brain involvement, and prior BRAF inhibitor utilization
  • Drug: PF-07284890
    PF-07284890 will be administered orally, daily for 21 consecutive days (21-day cycle)
    Other names:
    • ARRY-461
  • Drug: Binimetinib
    Binimetinib will be administered together with PF-07284890 orally, 45mg twice daily
    Other names:
    • Mektovi
Experimental
Expansion Phase (Part B, Cohort 4) 		PF-07284890 (at recommended dose from Part A) plus binimetinib in participants with BRAF V600 melanoma, with symptomatic brain involvement, and prior BRAF inhibitor utilization
  • Drug: PF-07284890
    PF-07284890 will be administered orally, daily for 21 consecutive days (21-day cycle)
    Other names:
    • ARRY-461
  • Drug: Binimetinib
    Binimetinib will be administered together with PF-07284890 orally, 45mg twice daily
    Other names:
    • Mektovi
Experimental
Expansion Phase (Part B Cohort 5) 		PF-07284890 (at recommended dose from Part A) plus binimetinib in participants with BRAF V600 solid tumor; history of or current leptomeningeal metastases; without disease in the brain; with disease in the brain that does not meet Cohorts 1-4; asymptomatic or symptomatic in the brain; primary brain tumors
  • Drug: PF-07284890
    PF-07284890 will be administered orally, daily for 21 consecutive days (21-day cycle)
    Other names:
    • ARRY-461
  • Drug: Binimetinib
    Binimetinib will be administered together with PF-07284890 orally, 45mg twice daily
    Other names:
    • Mektovi
Experimental
Expansion Phase Drug-Drug Interaction Substudy (Part B Optional Cohort 6) 		PF-07284890 (at recommended dose from Part A) plus binimetinib plus midazolam in participants with BRAF V600 solid tumor
  • Drug: PF-07284890
    PF-07284890 will be administered orally, daily for 21 consecutive days (21-day cycle)
    Other names:
    • ARRY-461
  • Drug: Binimetinib
    Binimetinib will be administered together with PF-07284890 orally, 45mg twice daily
    Other names:
    • Mektovi
  • Drug: Midazolam
    Midazolam will be administered 7 days before start of study drug, on Cycle 1 Day 1, and on Cycle 1 Day 15
Experimental
Expansion Phase (Part B Optional Cohort 7) 		PF-07284890 (at the recommended dose for expansion when administered with food) plus binimetinib in participants with BRAF V600 solid tumor
  • Drug: PF-07284890
    PF-07284890 will be administered orally, daily for 21 consecutive days (21-day cycle)
    Other names:
    • ARRY-461
  • Drug: Binimetinib
    Binimetinib will be administered together with PF-07284890 orally, 45mg twice daily
    Other names:
    • Mektovi

More Details

Status
Terminated
Sponsor
Pfizer

Study Contact

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.