A FIH Study of PF-07284890 in Participants With BRAF V600 Mutant Solid Tumors With and Without Brain Involvement

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

  • Malignant Melanoma
  • Carcinoma, Non-Small-Cell Lung
  • Brain Neoplasms, Primary
  • Brain Neoplasms
  • Malignant Neoplasms

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