Clinical trial NCT04543188: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: 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
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2020-09-10
Enrollment: 66
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Phase 1a - Number of participants with dose limiting toxicities (DLTs)
timeFrame: Cycle 1 (approximately 21 days / 3 weeks)
measure: Phase 1a - Number of participants with treatment emergent adverse events (AEs)
timeFrame: Baseline up to 30 days after last dose of study medication
measure: Phase 1a - Number of participants with clinically significant change from baseline in laboratory abnormalities
timeFrame: Baseline up to follow up visit (30 days after last dose of study treatment)
measure: Phase 1a - Number of dose interruptions, dose modifications, and discontinuations due to AEs
timeFrame: Baseline through approximately 12 months
measure: Phase 1b - Overall response
timeFrame: Baseline up to approximately 12 months
Secondary outcomes:
measure: Phase 1a: Maximum plasma concentration of PF-07284890 and binimetinib
timeFrame: 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)
measure: Phase 1a: Time to reach maximum plasma concentration of PF-07284890 and binimetinib
timeFrame: 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
measure: 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
timeFrame: 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
measure: Phase 1a: Terminal half-life (t1/2) of PF-07284890 and binimetinib
timeFrame: 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
measure: Phase 1a: Area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUCinf) of PF-07284890 and binimetinib
timeFrame: 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
measure: Phase 1a: Apparent oral clearance of PF-07284890 and binimetinib
timeFrame: 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
measure: Phase 1a: Volume of distribution of PF-07284890 and binimetinib
timeFrame: 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
measure: Phase 1a: Area under the plasma concentration-time curve over the dosing interval at steady state (AUCss,T) of PF-07284890 and binimetinib
timeFrame: 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
measure: Phase 1a: Trough plasma concentration at steady state (Css,min) of PF-07284890 and binimetinib
timeFrame: 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
measure: Phase 1a: Accumulation ratio (Rac) of PF-07284890 and binimetinib
timeFrame: 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
measure: Phase 1a: Overall response
timeFrame: Baseline up to approximately 12 months
measure: Phase 1b - Number of patients with treatment emergent AEs
timeFrame: Baseline up to 30 days after last dose of study medication
measure: Phase 1b - Number of participants with clinically significant change from baseline in laboratory abnormalities
timeFrame: Baseline up to follow up visit (30 days after last dose of study treatment)
measure: Phase 1b - Number of dose interruptions, dose modifications, and discontinuations due to AEs
timeFrame: Baseline through approximately 12 months
measure: Phase 1b: Maximum plasma concentration of PF-07284890 and binimetinib
timeFrame: 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
measure: Phase 1b: Time to reach maximum plasma concentration of PF-07284890 and binimetinib
timeFrame: 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
measure: 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
timeFrame: 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
measure: Phase 1b: Terminal half-life (t1/2) of PF-07284890 and binimetinib
timeFrame: 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
measure: Phase 1b: Area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUCinf) of PF-07284890 and binimetinib
timeFrame: 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
measure: Phase 1b: Apparent oral clearance of PF-07284890 and binimetinib
timeFrame: 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
measure: Phase 1b: Volume of distribution of PF-07284890 and binimetinib
timeFrame: 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
measure: Phase 1b: Area under the plasma concentration-time curve over the dosing interval at steady state (AUCss,T) of PF-07284890 and binimetinib
timeFrame: 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
measure: Phase 1b: Trough plasma concentration at steady state (Css,min) of PF-07284890 and binimetinib
timeFrame: 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
measure: Phase 1b: Accumulation ration (Rac) of PF-07284890 and binimetinib
timeFrame: 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
measure: Phase 1b: Disease Control Rate (DCR)
timeFrame: Every 6 weeks from time of enrollment up to 1 year, then every 12 weeks thereafter
measure: Phase 1b: Progression Free Survival (PFS)
timeFrame: Baseline to measured progressive disease (up to 12 months)
measure: Phase 1b: Overall Survival (OS)
timeFrame: Baseline to date of death from any cause (up to 12 months)
measure: Phase 1b: Duration of Response (DoR)
timeFrame: Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 1 year, then every 12 weeks thereafter
measure: Phase 1b: Time to Tumor Response (TTR)
timeFrame: Every 6 weeks from the time of enrollment up to 12 months
measure: Phase 1b: Maximum plasma concentration (Cmax) of CYP34A probe substrate midazolam
timeFrame: Day -7 (Lead-in); Cycle 1 Day 1 and Day 15 (predose, 0.5, 1, 2, 4, and 8 hours post dose)
measure: Phase 1b: Time to reach maximum plasma concentration (Tmax) of CYP3A4 probe substrate midazolam
timeFrame: Day -7 (Lead-in); Cycle 1 Day 1 and Day 15 (predose, 0.5, 1, 2, 4, and 8 hours post dose)
measure: 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
timeFrame: Day -7 (Lead-in); Cycle 1 Day 1 and Day 15 (predose, 0.5, 1, 2, 4, and 8 hours post dose)
measure: Phase 1b: Terminal half-life (t1/2) of CYP3A4 probe substrate midazolam
timeFrame: Day -7 (Lead-in); Cycle 1 Day 1 and Day 15 (predose, 0.5, 1, 2, 4, and 8 hours post dose)
measure: Phase 1b: Area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUCinf) of CYP3A4 probe substrate midazolam
timeFrame: Day -7 (Lead-in); Cycle 1 Day 1 and Day 15 (predose, 0.5, 1, 2, 4, and 8 hours post dose)
measure: Phase 1a: Apparent oral clearance (CL/F) of CYP3A4 probe substrate midazolam
timeFrame: Day -7 (Lead-in); Cycle 1 Day 1 and Day 15 (predose, 0.5, 1, 2, 4, and 8 hours post dose)
measure: Phase 1a: Volume of distribution (Vz/F) of CYP3A4 probe substrate midazolam
timeFrame: Day -7 (Lead-in); Cycle 1 Day 1 and Day 15 (predose, 0.5, 1, 2, 4, and 8 hours post dose)
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
state: California
city: Duarte
country: United States
facility: City of Hope Investigational Drug Services (IDS)
state: California
city: Los Angeles
country: United States
facility: Keck Hospital of USC
state: California
city: Los Angeles
country: United States
facility: LAC + USC Medical Center
state: California
city: Los Angeles
country: United States
facility: Norris Healthcare Center 3 (HC3)
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: USC/Roski Eye Institute
state: California
city: Pasadena
country: United States
facility: Keck Medical Center of USC Pasadena
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center
state: California
city: Orlando
country: United States
facility: Orlando Health Cancer Institute
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Tampa
country: United States
facility: Richard M Schulze Family Foundation Outpatient Center at McKinley Campus
state: Florida
city: Chicago
country: United States
facility: Northwestern Medical Group
state: Illinois
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Indianapolis
country: United States
facility: Community Health Network, Inc.
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Fairway
country: United States
facility: The University of Kansas Cancer Center - Investigational Drug Services
state: Kansas
city: Fairway
country: United States
facility: The University of Kansas Clinical Research Center
state: Kansas
city: Kansas City
country: United States
facility: The University of Kansas Hospital
state: Kansas
city: Westwood
country: United States
facility: The University of Kansas Cancer Center
state: Kansas
city: Baltimore
country: United States
facility: Johns Hopkins University / Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Ophthalmic Consultants of Boston Inc (OCB)
state: Massachusetts
city: Boston
country: United States
facility: Brigham & Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Imaging: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Brookline
country: United States
facility: Imaging: Brigham and Women's Radiology, Coolidge Corner Imaging
state: Massachusetts
city: Chestnut Hill
country: United States
facility: Imaging: Brigham and Women's Ambulatory Care
state: Massachusetts
city: Foxboro
country: United States
facility: Imaging: Brigham and Women's Mass General Healthcare Center
state: Massachusetts
city: Newton
country: United States
facility: Dana-Farber Cancer Institute - Chestnut Hill
state: Massachusetts
city: Farmington Hills
country: United States
facility: Michigan Health Professionals (PI Clinic)
state: Michigan
city: Sterling Heights
country: United States
facility: Revive Research Institute
state: Michigan
city: Saint Paul
country: United States
facility: HealthPartners Cancer Center at Regions Hospital
state: Minnesota
city: Saint Paul
country: United States
facility: Regions Hospital Pharmacy
state: Minnesota
city: Creve Coeur
country: United States
facility: Siteman Cancer Center - West County
state: Missouri
city: Florissant
country: United States
facility: Siteman Cancer Center - North County
state: Missouri
city: Saint Louis
country: United States
facility: Barnes-Jewish Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University Infusion Center Pharmacy
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Saint Louis
country: United States
facility: Siteman Cancer Center - South County
state: Missouri
city: Saint Peters
country: United States
facility: Siteman Cancer Center - St Peters
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack University Medical Center
state: New Jersey
city: Middletown
country: United States
facility: MSK Monmouth.
state: New Jersey
city: Commack
country: United States
facility: MSK Commack
state: New York
city: Harrison
country: United States
facility: MSKCC-Westchester (500 Westchester Ave.)
state: New York
city: New York
country: United States
facility: Laura and Isaac Perlmutter Cancer Center
state: New York
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: New York
country: United States
facility: NYU Langone Medical Center (Tisch Hospital)
state: New York
city: New York
country: United States
facility: NYU Langone Radiology- ACC East 41st street
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center - David H. Koch Center for Cancer Care (74th Street).
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center Rockefeller Outpatient Pavilion
state: New York
city: New York
country: United States
facility: Rockefeller Outpatient Pavilion (53rd Street)
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Chapel Hill
country: United States
facility: UNC Cancer Hospital Infusion Pharmacy
state: North Carolina
city: Chapel Hill
country: United States
facility: UNC Hospitals, The University of North Carolina at Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: Duke Eye Center
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center, Investigational Chemotherapy Services
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: Carl & Edyth Lindner Center for Research & Education at TCH and TCH Cancer Center
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: West Chester
country: United States
facility: West Chester Hospital
state: Ohio
city: Franklin
country: United States
facility: Tennessee Oncology PLLC
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon Research Institute - Pharmacy
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology PLLC
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Madison
country: United States
facility: University of Wisconsin Hospitals and Clinics
state: Wisconsin
city: Hamilton
country: Canada
facility: Hamilton Health Sciences-Juravinski Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Research Institute
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Haifa
country: Israel
facility: Rambam Health Care Campus
state: ?eif?
city: Petah-Tikva
country: Israel
facility: Rabin Medical Center
state: Hamerkaz
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
state: Hamerkaz
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center
state: Tell Abīb
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
state: Yerushalayim
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: