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

Primary Purpose

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

Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
PF-07284890
Binimetinib
Midazolam
Sponsored by
Pfizer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Malignant Melanoma focused on measuring Proto-Oncogene Proteins B-raf, Brain Neoplasms, Melanoma, Carcinoma, Non-Small-Cell Lung, Brain Diseases, Central Nervous System Neoplasms, Enzyme Inhibitors

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age ≥18 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 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:

  • 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

Sites / Locations

  • City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
  • City of Hope Investigational Drug Services (IDS)
  • Keck Hospital of USC
  • LAC + USC Medical Center
  • Norris Healthcare Center 3 (HC3)
  • USC/Norris Comprehensive Cancer Center
  • USC/Roski Eye Institute
  • Keck Medical Center of USC Pasadena
  • UCSF Helen Diller Family Comprehensive Cancer Center
  • UCSF Medical Center
  • Orlando Health Cancer Institute
  • Moffitt Cancer Center
  • Richard M Schulze Family Foundation Outpatient Center at McKinley Campus
  • Northwestern Medical Group
  • Northwestern Memorial Hospital
  • Community Health Network, Inc.
  • University of Iowa Hospitals and Clinics
  • The University of Kansas Cancer Center - Investigational Drug Services
  • The University of Kansas Clinical Research Center
  • The University of Kansas Hospital
  • The University of Kansas Cancer Center
  • Johns Hopkins University / Johns Hopkins Hospital
  • Massachusetts General Hospital
  • Ophthalmic Consultants of Boston Inc (OCB)
  • Brigham & Women's Hospital
  • Imaging: Brigham and Women's Hospital
  • Dana-Farber Cancer Institute
  • Imaging: Brigham and Women's Radiology, Coolidge Corner Imaging
  • Imaging: Brigham and Women's Ambulatory Care
  • Imaging: Brigham and Women's Mass General Healthcare Center
  • Dana-Farber Cancer Institute - Chestnut Hill
  • Michigan Health Professionals (PI Clinic)
  • Revive Research Institute
  • HealthPartners Cancer Center at Regions Hospital
  • Regions Hospital Pharmacy
  • Siteman Cancer Center - West County
  • Siteman Cancer Center - North County
  • Barnes-Jewish Hospital
  • Washington University Infusion Center Pharmacy
  • Washington University School of Medicine
  • Siteman Cancer Center - South County
  • Siteman Cancer Center - St Peters
  • Hackensack University Medical Center
  • John Theurer Cancer Center at Hackensack University Medical Center
  • Laura and Isaac Perlmutter Cancer Center
  • NYU Langone Health
  • NYU Langone Medical Center (Tisch Hospital)
  • NYU Langone Radiology- ACC East 41st street
  • Memorial Sloan Kettering Cancer Center Rockefeller Outpatient Pavilion
  • Memorial Sloan Kettering Cancer Center
  • UNC Cancer Hospital Infusion Pharmacy
  • UNC Hospitals, The University of North Carolina at Chapel Hill
  • Duke Eye Center
  • Duke University Medical Center, Investigational Chemotherapy Services
  • Duke University Medical Center
  • Carl & Edyth Lindner Center for Research & Education at TCH and TCH Cancer Center
  • University of Cincinnati Medical Center
  • West Chester Hospital
  • Tennessee Oncology PLLC
  • Sarah Cannon Research Institute - Pharmacy
  • Tennessee Oncology PLLC
  • The University of Texas MD Anderson Cancer Center
  • University of Wisconsin Hospitals and Clinics
  • Hamilton Health Sciences-Juravinski Cancer Centre
  • Sunnybrook Research Institute
  • Princess Margaret Cancer Centre
  • Jewish General Hospital
  • Rambam Health Care Campus
  • Rabin Medical Center
  • Sheba Medical Center
  • Sourasky Medical Center
  • Hadassah Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

PF-07284890 (Part A monotherapy)

PF-07284890+binimetinib (Part A combo-therapy)

Expansion Phase (Part B, Cohort 1)

Expansion Phase (Part B, Cohort 2)

Expansion Phase (Part B, Cohort 3)

Expansion Phase (Part B, Cohort 4)

Expansion Phase (Part B Cohort 5)

Expansion Phase Drug-Drug Interaction Substudy (Part B Optional Cohort 6)

Expansion Phase (Part B Optional Cohort 7)

Arm Description

Monotherapy dose escalation of PF-07284890

Combination dose escalation of PF-07284890 + binimetinib

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

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

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

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

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

PF-07284890 (at recommended dose from Part A) plus binimetinib plus midazolam in participants with BRAF V600 solid tumor

PF-07284890 (at the recommended dose for expansion when administered with food) plus binimetinib in participants with BRAF V600 solid tumor

Outcomes

Primary Outcome Measures

Phase 1a - Number of participants with dose limiting toxicities (DLTs)
DLTs will be evaluated during the first cycle (21 days) as both a single agent or in combination with binimetinib. The number of DLTs will be used to determine the maximum tolerated dose (MTD)/recommended dose for further study
Phase 1a - Number of participants with treatment emergent adverse events (AEs)
AEs as characterized by type, frequency, severity, timing, seriousness, and relationship to study therapy
Phase 1a - Number of participants with clinically significant change from baseline in laboratory abnormalities
Laboratory abnormalities as characterized by type, frequency, severity, and timing
Phase 1a - Number of dose interruptions, dose modifications, and discontinuations due to AEs
Incidence of dose interruptions, dose modifications, and discontinuations due to AEs
Phase 1b - Overall response
Response will be evaluated via radiographical tumor assessments by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and intracranial response by modified RECIST version 1.1 (mRECIST v 1.1) or RANO for primary brain tumors

Secondary Outcome Measures

Phase 1a: Maximum plasma concentration of PF-07284890 and binimetinib
Single dose (Cmax) and multiple dose (assuming steady state is achieved; Css,max) pharmacokinetic (PK) parameters
Phase 1a: Time to reach maximum plasma concentration of PF-07284890 and binimetinib
Single dose (Tmax) and multiple dose (assuming steady state is achieved; Tss,max) PK parameters
Phase 1a: Area under the plasma concentration-time curve from time 0 to the last time point of quantifiable concentration (AUClast) of PF-07284890 and binimetinib
Single dose PK parameter
Phase 1a: Terminal half-life (t1/2) of PF-07284890 and binimetinib
Single dose and multiple dose (assuming steady state is achieved and data permit) PK parameter
Phase 1a: Area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUCinf) of PF-07284890 and binimetinib
Single dose will be calculated as data permit PK parameter
Phase 1a: Apparent oral clearance of PF-07284890 and binimetinib
Single dose (CL/F) and multiple dose (assuming steady state is achieved and as data permit; CLss/F) PK parameter
Phase 1a: Volume of distribution of PF-07284890 and binimetinib
Single dose (Vz/F) and multiple dose (assuming steady state is achieved and as data permit; Vss/F) PK parameter
Phase 1a: Area under the plasma concentration-time curve over the dosing interval at steady state (AUCss,T) of PF-07284890 and binimetinib
Multiple dose (assuming steady state is achieved) PK parameter
Phase 1a: Trough plasma concentration at steady state (Css,min) of PF-07284890 and binimetinib
Multiple dose (assuming steady state is achieved) PK parameter
Phase 1a: Accumulation ratio (Rac) of PF-07284890 and binimetinib
Multiple dose (assuming steady state is achieved and as data permit) PK parameter
Phase 1a: Overall response
Response will be evaluated via radiographical tumor assessments by RECIST v1.1 and intracranial response by mRECIST v 1.1 or RANO for primary brain tumors
Phase 1b - Number of patients with treatment emergent AEs
AEs as characterized by type, frequency, severity, timing, seriousness, and relationship to study therapy
Phase 1b - Number of participants with clinically significant change from baseline in laboratory abnormalities
Laboratory abnormalities as characterized by type, frequency, severity, and timing
Phase 1b - Number of dose interruptions, dose modifications, and discontinuations due to AEs
Incidence of dose interruptions, dose modifications, and discontinuations due to AEs
Phase 1b: Maximum plasma concentration of PF-07284890 and binimetinib
Single dose (Cmax) and multiple dose (assuming steady state is achieved; Css,max) PK parameter
Phase 1b: Time to reach maximum plasma concentration of PF-07284890 and binimetinib
Single dose (Tmax) and multiple dose (assuming steady state is achieved; Tss,max) PK parameter
Phase 1b: Area under the plasma concentration-time curve from time 0 to the last time point of quantifiable concentration (AUClast) of PF-07284890 and binimetinib
Single dose PK parameter
Phase 1b: Terminal half-life (t1/2) of PF-07284890 and binimetinib
Single dose and multiple dose (assuming steady state is achieved and data permit) PK parameter
Phase 1b: Area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUCinf) of PF-07284890 and binimetinib
Single dose will be calculated as data permit PK parameter
Phase 1b: Apparent oral clearance of PF-07284890 and binimetinib
Single dose (CL/F) and multiple dose (assuming steady state is achieved and as data permit; CLss/F) PK parameter
Phase 1b: Volume of distribution of PF-07284890 and binimetinib
Single dose (Vz/F) and multiple dose (assuming steady state is achieved and as data permit; Vss/F) PK parameter
Phase 1b: Area under the plasma concentration-time curve over the dosing interval at steady state (AUCss,T) of PF-07284890 and binimetinib
Multiple dose (assuming steady state is achieved) PK parameter
Phase 1b: Trough plasma concentration at steady state (Css,min) of PF-07284890 and binimetinib
Multiple dose (assuming steady state is achieved) PK parameter
Phase 1b: Accumulation ration (Rac) of PF-07284890 and binimetinib
Multiple dose (assuming steady state is achieved and as data permit) PK parameter
Phase 1b: Disease Control Rate (DCR)
DCR is defined as the percent of participants with a confirmed complete response (CR), partial response (PR) or stable disease (SD) according to RECIST 1.1/RANO, at 6 weeks for both overall and intracranial
Phase 1b: Progression Free Survival (PFS)
The period from study entry until disease progression, death or date of last contact for both overall and intracranial.
Phase 1b: Overall Survival (OS)
Overall survival was the duration from enrollment to death. For participants who are alive, overall survival was censored at the last contact.
Phase 1b: Duration of Response (DoR)
Duration of response (DR) defined as time from start of first documented objective tumor response [Complete Response (CR) or Partial Response (PR)] to first documented objective tumor progression or death due to any cause, whichever occurs first.
Phase 1b: Time to Tumor Response (TTR)
TTR is defined as the time from first dose to first documentation of objective tumor response (CR or PR). For participants whose objective response (OR) proceeds from PR to CR, the onset of PR is taken as the onset of response. TTR will only be calculated for the subgroup of participants with a confirmed objective tumor response for both overall and intracranial
Phase 1b: Maximum plasma concentration (Cmax) of CYP34A probe substrate midazolam
PK parameter
Phase 1b: Time to reach maximum plasma concentration (Tmax) of CYP3A4 probe substrate midazolam
PK parameter
Phase 1b: Area under the plasma concentration-time curve from time 0 to the last time point of quantifiable concentration (AUClast) of CYP3A4 probe substrate midazolam
PK parameter
Phase 1b: Terminal half-life (t1/2) of CYP3A4 probe substrate midazolam
PK parameter as data permit
Phase 1b: Area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUCinf) of CYP3A4 probe substrate midazolam
PK parameter as data permit
Phase 1a: Apparent oral clearance (CL/F) of CYP3A4 probe substrate midazolam
PK parameter as data permit
Phase 1a: Volume of distribution (Vz/F) of CYP3A4 probe substrate midazolam
PK parameter as data permit

Full Information

First Posted
September 2, 2020
Last Updated
March 29, 2023
Sponsor
Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT04543188
Brief Title
A FIH Study of PF-07284890 in Participants With BRAF V600 Mutant Solid Tumors With and Without Brain Involvement
Official 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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 8, 2021 (Actual)
Primary Completion Date
November 15, 2023 (Anticipated)
Study Completion Date
November 15, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malignant Melanoma, Carcinoma, Non-Small-Cell Lung, Brain Neoplasms, Primary, Brain Neoplasms, Malignant Neoplasms
Keywords
Proto-Oncogene Proteins B-raf, Brain Neoplasms, Melanoma, Carcinoma, Non-Small-Cell Lung, Brain Diseases, Central Nervous System Neoplasms, Enzyme Inhibitors

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
PF-07284890 (Part A monotherapy)
Arm Type
Experimental
Arm Description
Monotherapy dose escalation of PF-07284890
Arm Title
PF-07284890+binimetinib (Part A combo-therapy)
Arm Type
Experimental
Arm Description
Combination dose escalation of PF-07284890 + binimetinib
Arm Title
Expansion Phase (Part B, Cohort 1)
Arm Type
Experimental
Arm Description
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
Arm Title
Expansion Phase (Part B, Cohort 2)
Arm Type
Experimental
Arm Description
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
Arm Title
Expansion Phase (Part B, Cohort 3)
Arm Type
Experimental
Arm Description
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
Arm Title
Expansion Phase (Part B, Cohort 4)
Arm Type
Experimental
Arm Description
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
Arm Title
Expansion Phase (Part B Cohort 5)
Arm Type
Experimental
Arm Description
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
Arm Title
Expansion Phase Drug-Drug Interaction Substudy (Part B Optional Cohort 6)
Arm Type
Experimental
Arm Description
PF-07284890 (at recommended dose from Part A) plus binimetinib plus midazolam in participants with BRAF V600 solid tumor
Arm Title
Expansion Phase (Part B Optional Cohort 7)
Arm Type
Experimental
Arm Description
PF-07284890 (at the recommended dose for expansion when administered with food) plus binimetinib in participants with BRAF V600 solid tumor
Intervention Type
Drug
Intervention Name(s)
PF-07284890
Other Intervention Name(s)
ARRY-461
Intervention Description
PF-07284890 will be administered orally, daily for 21 consecutive days (21-day cycle)
Intervention Type
Drug
Intervention Name(s)
Binimetinib
Other Intervention Name(s)
Mektovi
Intervention Description
Binimetinib will be administered together with PF-07284890 orally, 45mg twice daily
Intervention Type
Drug
Intervention Name(s)
Midazolam
Intervention Description
Midazolam will be administered 7 days before start of study drug, on Cycle 1 Day 1, and on Cycle 1 Day 15
Primary Outcome Measure Information:
Title
Phase 1a - Number of participants with dose limiting toxicities (DLTs)
Description
DLTs will be evaluated during the first cycle (21 days) as both a single agent or in combination with binimetinib. The number of DLTs will be used to determine the maximum tolerated dose (MTD)/recommended dose for further study
Time Frame
Cycle 1 (approximately 21 days / 3 weeks)
Title
Phase 1a - Number of participants with treatment emergent adverse events (AEs)
Description
AEs as characterized by type, frequency, severity, timing, seriousness, and relationship to study therapy
Time Frame
Baseline up to 30 days after last dose of study medication
Title
Phase 1a - Number of participants with clinically significant change from baseline in laboratory abnormalities
Description
Laboratory abnormalities as characterized by type, frequency, severity, and timing
Time Frame
Baseline up to follow up visit (30 days after last dose of study treatment)
Title
Phase 1a - Number of dose interruptions, dose modifications, and discontinuations due to AEs
Description
Incidence of dose interruptions, dose modifications, and discontinuations due to AEs
Time Frame
Baseline through approximately 12 months
Title
Phase 1b - Overall response
Description
Response will be evaluated via radiographical tumor assessments by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and intracranial response by modified RECIST version 1.1 (mRECIST v 1.1) or RANO for primary brain tumors
Time Frame
Baseline up to approximately 12 months
Secondary Outcome Measure Information:
Title
Phase 1a: Maximum plasma concentration of PF-07284890 and binimetinib
Description
Single dose (Cmax) and multiple dose (assuming steady state is achieved; Css,max) pharmacokinetic (PK) parameters
Time Frame
Cycle 1 Day 1 (predose, 1, 2, 4, 6, 8, and 24 hours (Day 2) post dose); Cycle 1 Day 15 (predose, 1, 2, 4, 6, and 8 hours post dose); Cycles 2-6 Day 1 (predose and 2 hours post dose); End of Treatment (EOT)
Title
Phase 1a: Time to reach maximum plasma concentration of PF-07284890 and binimetinib
Description
Single dose (Tmax) and multiple dose (assuming steady state is achieved; Tss,max) PK parameters
Time Frame
Cycle 1 Day 1 (predose, 1, 2, 4, 6, 8, and 24 hours (Day 2) post dose); Cycle 1 Day 15 (predose, 1, 2, 4, 6, and 8 hours post dose); Cycles 2-6 Day 1 (predose and 2 hours post dose); EOT
Title
Phase 1a: Area under the plasma concentration-time curve from time 0 to the last time point of quantifiable concentration (AUClast) of PF-07284890 and binimetinib
Description
Single dose PK parameter
Time Frame
Cycle 1 Day 1 (predose, 1, 2, 4, 6, 8, and 24 hours (Day 2) post dose); Cycle 1 Day 15 (predose, 1, 2, 4, 6, and 8 hours post dose); Cycles 2-6 Day 1 (predose and 2 hours post dose); EOT
Title
Phase 1a: Terminal half-life (t1/2) of PF-07284890 and binimetinib
Description
Single dose and multiple dose (assuming steady state is achieved and data permit) PK parameter
Time Frame
Cycle 1 Day 1 (predose, 1, 2, 4, 6, 8, and 24 hours (Day 2) post dose); Cycle 1 Day 15 (predose, 1, 2, 4, 6, and 8 hours post dose); Cycles 2-6 Day 1 (predose and 2 hours post dose); EOT
Title
Phase 1a: Area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUCinf) of PF-07284890 and binimetinib
Description
Single dose will be calculated as data permit PK parameter
Time Frame
Cycle 1 Day 1 (predose, 1, 2, 4, 6, 8, and 24 hours (Day 2) post dose); Cycle 1 Day 15 (predose, 1, 2, 4, 6, and 8 hours post dose); Cycles 2-6 Day 1 (predose and 2 hours post dose); EOT
Title
Phase 1a: Apparent oral clearance of PF-07284890 and binimetinib
Description
Single dose (CL/F) and multiple dose (assuming steady state is achieved and as data permit; CLss/F) PK parameter
Time Frame
Cycle 1 Day 1 (predose, 1, 2, 4, 6, 8, and 24 hours (Day 2) post dose); Cycle 1 Day 15 (predose, 1, 2, 4, 6, and 8 hours post dose); Cycles 2-6 Day 1 (predose and 2 hours post dose); EOT
Title
Phase 1a: Volume of distribution of PF-07284890 and binimetinib
Description
Single dose (Vz/F) and multiple dose (assuming steady state is achieved and as data permit; Vss/F) PK parameter
Time Frame
Cycle 1 Day 1 (predose, 1, 2, 4, 6, 8, and 24 hours (Day 2) post dose); Cycle 1 Day 15 (predose, 1, 2, 4, 6, and 8 hours post dose); Cycles 2-6 Day 1 (predose and 2 hours post dose); EOT
Title
Phase 1a: Area under the plasma concentration-time curve over the dosing interval at steady state (AUCss,T) of PF-07284890 and binimetinib
Description
Multiple dose (assuming steady state is achieved) PK parameter
Time Frame
Cycle 1 Day 1 (predose, 1, 2, 4, 6, 8, and 24 hours (Day 2) post dose); Cycle 1 Day 15 (predose, 1, 2, 4, 6, and 8 hours post dose); Cycles 2-6 Day 1 (predose and 2 hours post dose); EOT
Title
Phase 1a: Trough plasma concentration at steady state (Css,min) of PF-07284890 and binimetinib
Description
Multiple dose (assuming steady state is achieved) PK parameter
Time Frame
Cycle 1 Day 1 (predose, 1, 2, 4, 6, 8, and 24 hours (Day 2) post dose); Cycle 1 Day 15 (predose, 1, 2, 4, 6, and 8 hours post dose); Cycles 2-6 Day 1 (predose and 2 hours post dose); EOT
Title
Phase 1a: Accumulation ratio (Rac) of PF-07284890 and binimetinib
Description
Multiple dose (assuming steady state is achieved and as data permit) PK parameter
Time Frame
Cycle 1 Day 1 (predose, 1, 2, 4, 6, 8, and 24 hours (Day 2) post dose); Cycle 1 Day 15 (predose, 1, 2, 4, 6, and 8 hours post dose); Cycles 2-6 Day 1 (predose and 2 hours post dose); EOT
Title
Phase 1a: Overall response
Description
Response will be evaluated via radiographical tumor assessments by RECIST v1.1 and intracranial response by mRECIST v 1.1 or RANO for primary brain tumors
Time Frame
Baseline up to approximately 12 months
Title
Phase 1b - Number of patients with treatment emergent AEs
Description
AEs as characterized by type, frequency, severity, timing, seriousness, and relationship to study therapy
Time Frame
Baseline up to 30 days after last dose of study medication
Title
Phase 1b - Number of participants with clinically significant change from baseline in laboratory abnormalities
Description
Laboratory abnormalities as characterized by type, frequency, severity, and timing
Time Frame
Baseline up to follow up visit (30 days after last dose of study treatment)
Title
Phase 1b - Number of dose interruptions, dose modifications, and discontinuations due to AEs
Description
Incidence of dose interruptions, dose modifications, and discontinuations due to AEs
Time Frame
Baseline through approximately 12 months
Title
Phase 1b: Maximum plasma concentration of PF-07284890 and binimetinib
Description
Single dose (Cmax) and multiple dose (assuming steady state is achieved; Css,max) PK parameter
Time Frame
Cycle 1 Day 1 and 15 (predose, 1, 2, and 4 hours post dose); Cycles 2-6 Day 1 (predose and 2 hours post dose); EOT
Title
Phase 1b: Time to reach maximum plasma concentration of PF-07284890 and binimetinib
Description
Single dose (Tmax) and multiple dose (assuming steady state is achieved; Tss,max) PK parameter
Time Frame
Cycle 1 Day 1 and 15 (predose, 1, 2, and 4 hours post dose); Cycles 2-6 Day 1 (predose and 2 hours post dose); EOT
Title
Phase 1b: Area under the plasma concentration-time curve from time 0 to the last time point of quantifiable concentration (AUClast) of PF-07284890 and binimetinib
Description
Single dose PK parameter
Time Frame
Cycle 1 Day 1 and 15 (predose, 1, 2, and 4 hours post dose); Cycles 2-6 Day 1 (predose and 2 hours post dose); EOT
Title
Phase 1b: Terminal half-life (t1/2) of PF-07284890 and binimetinib
Description
Single dose and multiple dose (assuming steady state is achieved and data permit) PK parameter
Time Frame
Cycle 1 Day 1 and 15 (predose, 1, 2, and 4 hours post dose); Cycles 2-6 Day 1 (predose and 2 hours post dose); EOT
Title
Phase 1b: Area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUCinf) of PF-07284890 and binimetinib
Description
Single dose will be calculated as data permit PK parameter
Time Frame
Cycle 1 Day 1 and 15 (predose, 1, 2, and 4 hours post dose); Cycles 2-6 Day 1 (predose and 2 hours post dose); EOT
Title
Phase 1b: Apparent oral clearance of PF-07284890 and binimetinib
Description
Single dose (CL/F) and multiple dose (assuming steady state is achieved and as data permit; CLss/F) PK parameter
Time Frame
Cycle 1 Day 1 and 15 (predose, 1, 2, and 4 hours post dose); Cycles 2-6 Day 1 (predose and 2 hours post dose); EOT
Title
Phase 1b: Volume of distribution of PF-07284890 and binimetinib
Description
Single dose (Vz/F) and multiple dose (assuming steady state is achieved and as data permit; Vss/F) PK parameter
Time Frame
Cycle 1 Day 1 and 15 (predose, 1, 2, and 4 hours post dose); Cycles 2-6 Day 1 (predose and 2 hours post dose); EOT
Title
Phase 1b: Area under the plasma concentration-time curve over the dosing interval at steady state (AUCss,T) of PF-07284890 and binimetinib
Description
Multiple dose (assuming steady state is achieved) PK parameter
Time Frame
Cycle 1 Day 1 and 15 (predose, 1, 2, and 4 hours post dose); Cycles 2-6 Day 1 (predose and 2 hours post dose); EOT
Title
Phase 1b: Trough plasma concentration at steady state (Css,min) of PF-07284890 and binimetinib
Description
Multiple dose (assuming steady state is achieved) PK parameter
Time Frame
Cycle 1 Day 1 and 15 (predose, 1, 2, and 4 hours post dose); Cycles 2-6 Day 1 (predose and 2 hours post dose); EOT
Title
Phase 1b: Accumulation ration (Rac) of PF-07284890 and binimetinib
Description
Multiple dose (assuming steady state is achieved and as data permit) PK parameter
Time Frame
Cycle 1 Day 1 and 15 (predose, 1, 2, and 4 hours post dose); Cycles 2-6 Day 1 (predose and 2 hours post dose); EOT
Title
Phase 1b: Disease Control Rate (DCR)
Description
DCR is defined as the percent of participants with a confirmed complete response (CR), partial response (PR) or stable disease (SD) according to RECIST 1.1/RANO, at 6 weeks for both overall and intracranial
Time Frame
Every 6 weeks from time of enrollment up to 1 year, then every 12 weeks thereafter
Title
Phase 1b: Progression Free Survival (PFS)
Description
The period from study entry until disease progression, death or date of last contact for both overall and intracranial.
Time Frame
Baseline to measured progressive disease (up to 12 months)
Title
Phase 1b: Overall Survival (OS)
Description
Overall survival was the duration from enrollment to death. For participants who are alive, overall survival was censored at the last contact.
Time Frame
Baseline to date of death from any cause (up to 12 months)
Title
Phase 1b: Duration of Response (DoR)
Description
Duration of response (DR) defined as time from start of first documented objective tumor response [Complete Response (CR) or Partial Response (PR)] to first documented objective tumor progression or death due to any cause, whichever occurs first.
Time Frame
Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 1 year, then every 12 weeks thereafter
Title
Phase 1b: Time to Tumor Response (TTR)
Description
TTR is defined as the time from first dose to first documentation of objective tumor response (CR or PR). For participants whose objective response (OR) proceeds from PR to CR, the onset of PR is taken as the onset of response. TTR will only be calculated for the subgroup of participants with a confirmed objective tumor response for both overall and intracranial
Time Frame
Every 6 weeks from the time of enrollment up to 12 months
Title
Phase 1b: Maximum plasma concentration (Cmax) of CYP34A probe substrate midazolam
Description
PK parameter
Time Frame
Day -7 (Lead-in); Cycle 1 Day 1 and Day 15 (predose, 0.5, 1, 2, 4, and 8 hours post dose)
Title
Phase 1b: Time to reach maximum plasma concentration (Tmax) of CYP3A4 probe substrate midazolam
Description
PK parameter
Time Frame
Day -7 (Lead-in); Cycle 1 Day 1 and Day 15 (predose, 0.5, 1, 2, 4, and 8 hours post dose)
Title
Phase 1b: Area under the plasma concentration-time curve from time 0 to the last time point of quantifiable concentration (AUClast) of CYP3A4 probe substrate midazolam
Description
PK parameter
Time Frame
Day -7 (Lead-in); Cycle 1 Day 1 and Day 15 (predose, 0.5, 1, 2, 4, and 8 hours post dose)
Title
Phase 1b: Terminal half-life (t1/2) of CYP3A4 probe substrate midazolam
Description
PK parameter as data permit
Time Frame
Day -7 (Lead-in); Cycle 1 Day 1 and Day 15 (predose, 0.5, 1, 2, 4, and 8 hours post dose)
Title
Phase 1b: Area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUCinf) of CYP3A4 probe substrate midazolam
Description
PK parameter as data permit
Time Frame
Day -7 (Lead-in); Cycle 1 Day 1 and Day 15 (predose, 0.5, 1, 2, 4, and 8 hours post dose)
Title
Phase 1a: Apparent oral clearance (CL/F) of CYP3A4 probe substrate midazolam
Description
PK parameter as data permit
Time Frame
Day -7 (Lead-in); Cycle 1 Day 1 and Day 15 (predose, 0.5, 1, 2, 4, and 8 hours post dose)
Title
Phase 1a: Volume of distribution (Vz/F) of CYP3A4 probe substrate midazolam
Description
PK parameter as data permit
Time Frame
Day -7 (Lead-in); Cycle 1 Day 1 and Day 15 (predose, 0.5, 1, 2, 4, and 8 hours post dose)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
City of Hope Investigational Drug Services (IDS)
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
Keck Hospital of USC
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
LAC + USC Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Norris Healthcare Center 3 (HC3)
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
USC/Norris Comprehensive Cancer Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
USC/Roski Eye Institute
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Keck Medical Center of USC Pasadena
City
Pasadena
State/Province
California
ZIP/Postal Code
91105
Country
United States
Facility Name
UCSF Helen Diller Family Comprehensive Cancer Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
UCSF Medical Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
Facility Name
Orlando Health Cancer Institute
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Richard M Schulze Family Foundation Outpatient Center at McKinley Campus
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Northwestern Medical Group
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Northwestern Memorial Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Community Health Network, Inc.
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46250
Country
United States
Facility Name
University of Iowa Hospitals and Clinics
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
The University of Kansas Cancer Center - Investigational Drug Services
City
Fairway
State/Province
Kansas
ZIP/Postal Code
66205
Country
United States
Facility Name
The University of Kansas Clinical Research Center
City
Fairway
State/Province
Kansas
ZIP/Postal Code
66205
Country
United States
Facility Name
The University of Kansas Hospital
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
The University of Kansas Cancer Center
City
Westwood
State/Province
Kansas
ZIP/Postal Code
66205
Country
United States
Facility Name
Johns Hopkins University / Johns Hopkins Hospital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Ophthalmic Consultants of Boston Inc (OCB)
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Brigham & Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Imaging: Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Imaging: Brigham and Women's Radiology, Coolidge Corner Imaging
City
Brookline
State/Province
Massachusetts
ZIP/Postal Code
02446
Country
United States
Facility Name
Imaging: Brigham and Women's Ambulatory Care
City
Chestnut Hill
State/Province
Massachusetts
ZIP/Postal Code
02467
Country
United States
Facility Name
Imaging: Brigham and Women's Mass General Healthcare Center
City
Foxboro
State/Province
Massachusetts
ZIP/Postal Code
02035
Country
United States
Facility Name
Dana-Farber Cancer Institute - Chestnut Hill
City
Newton
State/Province
Massachusetts
ZIP/Postal Code
02459
Country
United States
Facility Name
Michigan Health Professionals (PI Clinic)
City
Farmington Hills
State/Province
Michigan
ZIP/Postal Code
48334
Country
United States
Facility Name
Revive Research Institute
City
Sterling Heights
State/Province
Michigan
ZIP/Postal Code
48314
Country
United States
Facility Name
HealthPartners Cancer Center at Regions Hospital
City
Saint Paul
State/Province
Minnesota
ZIP/Postal Code
55101
Country
United States
Facility Name
Regions Hospital Pharmacy
City
Saint Paul
State/Province
Minnesota
ZIP/Postal Code
55101
Country
United States
Facility Name
Siteman Cancer Center - West County
City
Creve Coeur
State/Province
Missouri
ZIP/Postal Code
63141
Country
United States
Facility Name
Siteman Cancer Center - North County
City
Florissant
State/Province
Missouri
ZIP/Postal Code
63031
Country
United States
Facility Name
Barnes-Jewish Hospital
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Washington University Infusion Center Pharmacy
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Siteman Cancer Center - South County
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63129
Country
United States
Facility Name
Siteman Cancer Center - St Peters
City
Saint Peters
State/Province
Missouri
ZIP/Postal Code
63376
Country
United States
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
John Theurer Cancer Center at Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Laura and Isaac Perlmutter Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
NYU Langone Health
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
NYU Langone Medical Center (Tisch Hospital)
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
NYU Langone Radiology- ACC East 41st street
City
New York
State/Province
New York
ZIP/Postal Code
10017
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center Rockefeller Outpatient Pavilion
City
New York
State/Province
New York
ZIP/Postal Code
10022
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
UNC Cancer Hospital Infusion Pharmacy
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27514
Country
United States
Facility Name
UNC Hospitals, The University of North Carolina at Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27514
Country
United States
Facility Name
Duke Eye Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Facility Name
Duke University Medical Center, Investigational Chemotherapy Services
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Carl & Edyth Lindner Center for Research & Education at TCH and TCH Cancer Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Facility Name
University of Cincinnati Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Facility Name
West Chester Hospital
City
West Chester
State/Province
Ohio
ZIP/Postal Code
45069
Country
United States
Facility Name
Tennessee Oncology PLLC
City
Franklin
State/Province
Tennessee
ZIP/Postal Code
37067
Country
United States
Facility Name
Sarah Cannon Research Institute - Pharmacy
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Tennessee Oncology PLLC
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
The University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Wisconsin Hospitals and Clinics
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
Facility Name
Hamilton Health Sciences-Juravinski Cancer Centre
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8V5C2
Country
Canada
Facility Name
Sunnybrook Research Institute
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N 3M5
Country
Canada
Facility Name
Princess Margaret Cancer Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
Jewish General Hospital
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1E2
Country
Canada
Facility Name
Rambam Health Care Campus
City
Haifa
State/Province
?eif?
ZIP/Postal Code
3109601
Country
Israel
Facility Name
Rabin Medical Center
City
Petah-Tikva
State/Province
Hamerkaz
ZIP/Postal Code
49100
Country
Israel
Facility Name
Sheba Medical Center
City
Ramat Gan
State/Province
Hamerkaz
ZIP/Postal Code
5262100
Country
Israel
Facility Name
Sourasky Medical Center
City
Tel Aviv
State/Province
Tell Abīb
ZIP/Postal Code
6423906
Country
Israel
Facility Name
Hadassah Medical Center
City
Jerusalem
State/Province
Yerushalayim
ZIP/Postal Code
9112001
Country
Israel

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
Links:
URL
https://pmiform.com/clinical-trial-info-request?StudyID=C4471001
Description
To obtain contact information for a study center near you, click here.

Learn more about this trial

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

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