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

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ClinicalTrials.gov Identifier: NCT04543188
Recruitment Status : Recruiting
First Posted : September 10, 2020
Last Update Posted : March 10, 2021
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE September 2, 2020
First Posted Date  ICMJE September 10, 2020
Last Update Posted Date March 10, 2021
Actual Study Start Date  ICMJE January 8, 2021
Estimated Primary Completion Date September 30, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 2, 2020)
  • Phase 1a - Number of participants with dose limiting toxicities (DLTs) [ Time Frame: Cycle 1 (approximately 21 days / 3 weeks) ]
    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) [ Time Frame: Baseline up to 30 days after last dose of study medication ]
    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 [ Time Frame: Baseline up to follow up visit (30 days after last dose of study treatment) ]
    Laboratory abnormalities as characterized by type, frequency, severity, and timing
  • Phase 1a - Number of dose interruptions, dose modifications, and discontinuations due to AEs [ Time Frame: Baseline through approximately 12 months ]
    Incidence of dose interruptions, dose modifications, and discontinuations due to AEs
  • Phase 1b - Overall response [ Time Frame: Baseline up to approximately 12 months ]
    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)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 8, 2021)
  • Phase 1a: Maximum plasma concentration of PF-07284890 and binimetinib [ 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) ]
    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 [ 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 ]
    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 [ 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 ]
    Single dose PK parameter
  • Phase 1a: Terminal half-life (t1/2) of PF-07284890 and binimetinib [ 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 ]
    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 [ 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 ]
    Single dose will be calculated as data permit PK parameter
  • Phase 1a: Apparent oral clearance of PF-07284890 and binimetinib [ 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 ]
    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 [ 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 ]
    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 [ 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 ]
    Multiple dose (assuming steady state is achieved) PK parameter
  • Phase 1a: Trough plasma concentration at steady state (Css,min) of PF-07284890 and binimetinib [ 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 ]
    Multiple dose (assuming steady state is achieved) PK parameter
  • Phase 1a: Accumulation ratio (Rac) of PF-07284890 and binimetinib [ 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 ]
    Multiple dose (assuming steady state is achieved and as data permit) PK parameter
  • Phase 1a: Overall response [ Time Frame: Baseline up to approximately 12 months ]
    Response will be evaluated via radiographical tumor assessments by RECIST v1.1 and intracranial response by mRECIST v 1.1
  • Phase 1b - Number of patients with treatment emergent AEs [ Time Frame: Baseline up to 30 days after last dose of study medication ]
    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 [ Time Frame: Baseline up to follow up visit (30 days after last dose of study treatment) ]
    Laboratory abnormalities as characterized by type, frequency, severity, and timing
  • Phase 1b - Number of dose interruptions, dose modifications, and discontinations due to AEs [ Time Frame: Baseline through approximately 12 months ]
    Incidence of dose interruptions, dose modifications, and discontinuations due to AEs
  • Phase 1b: Maximum plasma concentration of PF-07284890 and binimetinib [ 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 ]
    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 [ 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 ]
    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 [ 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 ]
    Single dose PK parameter
  • Phase 1b: Terminal half-life (t1/2) of PF-07284890 and binimetinib [ 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 ]
    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 [ 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 ]
    Single dose will be calculated as data permit PK parameter
  • Phase 1b: Apparent oral clearance of PF-07284890 and binimetinib [ 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 ]
    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 [ 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 ]
    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 [ 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 ]
    Multiple dose (assuming steady state is achieved) PK parameter
  • Phase 1b: Trough plasma concentration at steady state (Css,min) of PF-07284890 and binimetinib [ 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 ]
    Multiple dose (assuming steady state is achieved) PK parameter
  • Phase 1b: Accumulation ration (Rac) of PF-07284890 and binimetinib [ 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 ]
    Multiple dose (assuming steady state is achieved and as data permit) PK parameter
  • Phase 1b: Disease Control Rate (DCR) [ Time Frame: Every 6 weeks from time of enrollment up to 1 year, then every 12 weeks thereafter ]
    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, at 6 weeks for both overall and intracranial
  • Phase 1b: Progression Free Survival (PFS) [ Time Frame: Baseline to measured progressive disease (up to 12 months) ]
    The period from study entry until disease progression, death or date of last contact for both overall and intracranial.
  • Phase 1b: Overall Survival (OS) [ Time Frame: Baseline to date of death from any cause (up to 12 months) ]
    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) [ Time Frame: Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 1 year, then every 12 weeks thereafter ]
    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) [ Time Frame: Every 6 weeks from the time of enrollment up to 12 months ]
    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 [ Time Frame: Day -7 (Lead-in); Cycle 1 Day 1 and Day 15 (predose, 0.5, 1, 2, 4, and 8 hours post dose) ]
    PK parameter
  • Phase 1b: Time to reach maximum plasma concentration (Tmax) of CYP3A4 probe substrate midazolam [ Time Frame: Day -7 (Lead-in); Cycle 1 Day 1 and Day 15 (predose, 0.5, 1, 2, 4, and 8 hours post dose) ]
    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 [ Time Frame: Day -7 (Lead-in); Cycle 1 Day 1 and Day 15 (predose, 0.5, 1, 2, 4, and 8 hours post dose) ]
    PK parameter
  • Phase 1b: Terminal half-life (t1/2) of CYP3A4 probe substrate midazolam [ Time Frame: Day -7 (Lead-in); Cycle 1 Day 1 and Day 15 (predose, 0.5, 1, 2, 4, and 8 hours post dose) ]
    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 [ Time Frame: Day -7 (Lead-in); Cycle 1 Day 1 and Day 15 (predose, 0.5, 1, 2, 4, and 8 hours post dose) ]
    PK parameter as data permit
  • Phase 1a: Apparent oral clearance (CL/F) of CYP3A4 probe substrate midazolam [ Time Frame: Day -7 (Lead-in); Cycle 1 Day 1 and Day 15 (predose, 0.5, 1, 2, 4, and 8 hours post dose) ]
    PK parameter as data permit
  • Phase 1a: Volume of distribution (Vz/F) of CYP3A4 probe substrate midazolam [ Time Frame: Day -7 (Lead-in); Cycle 1 Day 1 and Day 15 (predose, 0.5, 1, 2, 4, and 8 hours post dose) ]
    PK parameter as data permit
Original Secondary Outcome Measures  ICMJE
 (submitted: September 2, 2020)
  • Phase 1a: Maximum plasma concentration of PF-07284890 and binimetinib [ 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) ]
    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 [ 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 ]
    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 [ 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 ]
    Single dose PK parameter
  • Phase 1a: Terminal half-life (t1/2) of PF-07284890 and binimetinib [ 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 ]
    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 [ 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 ]
    Single dose will be calculated as data permit PK parameter
  • Phase 1a: Apparent oral clearance of PF-07284890 and binimetinib [ 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 ]
    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 [ 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 ]
    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 [ 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 ]
    Multiple dose (assuming steady state is achieved) PK parameter
  • Phase 1a: Trough plasma concentration at steady state (Css,min) of PF-07284890 and binimetinib [ 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 ]
    Multiple dose (assuming steady state is achieved) PK parameter
  • Phase 1a: Accumulation ratio (Rac) of PF-07284890 and binimetinib [ 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 ]
    Multiple dose (assuming steady state is achieved and as data permit) PK parameter
  • Phase 1a: Overall response [ Time Frame: Baseline up to approximately 12 months ]
    Response will be evaluated via radiographical tumor assessments by RECIST v1.1 and intracranial response by mRECIST v 1.1
  • Phase 1b - Number of patients with treatment emergent AEs [ Time Frame: Baseline up to 30 days after last dose of study medication ]
    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 [ Time Frame: Baseline up to follow up visit (30 days after last dose of study treatment) ]
    Laboratory abnormalities as characterized by type, frequency, severity, and timing
  • Phase 1b - Number of dose interruptions, dose modifications, and discontinuations due to AEs [ Time Frame: Baseline through approximately 12 months ]
    Incidence of dose interruptions, dose modifications, and discontinuations due to AEs
  • Phase 1b: Maximum plasma concentration of PF-07284890 and binimetinib [ 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 ]
    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 [ 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 ]
    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 [ 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 ]
    Single dose PK parameter
  • Phase 1b: Terminal half-life (t1/2) of PF-07284890 and binimetinib [ 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 ]
    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 [ 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 ]
    Single dose will be calculated as data permit PK parameter
  • Phase 1b: Apparent oral clearance of PF-07284890 and binimetinib [ 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 ]
    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 [ 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 ]
    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 [ 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 ]
    Multiple dose (assuming steady state is achieved) PK parameter
  • Phase 1b: Trough plasma concentration at steady state (Css,min) of PF-07284890 and binimetinib [ 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 ]
    Multiple dose (assuming steady state is achieved) PK parameter
  • Phase 1b: Accumulation ration (Rac) of PF-07284890 and binimetinib [ 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 ]
    Multiple dose (assuming steady state is achieved and as data permit) PK parameter
  • Phase 1b: Disease Control Rate (DCR) [ Time Frame: Every 6 weeks from time of enrollment up to 1 year, then every 12 weeks thereafter ]
    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, at 6 weeks for both overall and intracranial
  • Phase 1b: Progression Free Survival (PFS) [ Time Frame: Baseline to measured progressive disease (up to 12 months) ]
    The period from study entry until disease progression, death or date of last contact for both overall and intracranial.
  • Phase 1b: Overall Survival (OS) [ Time Frame: Baseline to date of death from any cause (up to 12 months) ]
    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) [ Time Frame: Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 1 year, then every 12 weeks thereafter ]
    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) [ Time Frame: Every 6 weeks from the time of enrollment up to 12 months ]
    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 [ Time Frame: Day -7 (Lead-in); Cycle 1 Day 1 and Day 15 (predose, 0.5, 1, 2, 4, and 8 hours post dose) ]
    PK parameter
  • Phase 1b: Time to reach maximum plasma concentration (Tmax) of CYP3A4 probe substrate midazolam [ Time Frame: Day -7 (Lead-in); Cycle 1 Day 1 and Day 15 (predose, 0.5, 1, 2, 4, and 8 hours post dose) ]
    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 [ Time Frame: Day -7 (Lead-in); Cycle 1 Day 1 and Day 15 (predose, 0.5, 1, 2, 4, and 8 hours post dose) ]
    PK parameter
  • Phase 1b: Terminal half-life (t1/2) of CYP3A4 probe substrate midazolam [ Time Frame: Day -7 (Lead-in); Cycle 1 Day 1 and Day 15 (predose, 0.5, 1, 2, 4, and 8 hours post dose) ]
    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 [ Time Frame: Day -7 (Lead-in); Cycle 1 Day 1 and Day 15 (predose, 0.5, 1, 2, 4, and 8 hours post dose) ]
    PK parameter as data permit
  • Phase 1a: Apparent oral clearance (CL/F) of CYP3A4 probe substrate midazolam [ Time Frame: Day -7 (Lead-in); Cycle 1 Day 1 and Day 15 (predose, 0.5, 1, 2, 4, and 8 hours post dose) ]
    PK parameter as data permit
  • Phase 1a: Volume of distribution (Vz/F) of CYP3A4 probe substrate midazolam [ Time Frame: Day -7 (Lead-in); Cycle 1 Day 1 and Day 15 (predose, 0.5, 1, 2, 4, and 8 hours post dose) ]
    PK parameter as data permit
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A FIH Study of PF-07284890 in Participants With BRAF V600 Mutant Solid Tumors With and Without Brain Involvement
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Malignant Melanoma
  • Carcinoma, Non-Small-Cell Lung
  • Brain Neoplasms, Primary
  • Brain Neoplasms
  • Malignant Neoplasms
Intervention  ICMJE
  • Drug: PF-07284890
    PF-07284890 will be administered orally, daily for 21 consecutive days (21-day cycle)
    Other Name: ARRY-461
  • Drug: Binimetinib
    Binimetinib will be administered together with PF-07284890 orally, 45mg twice daily
    Other Name: 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
Study Arms  ICMJE
  • Experimental: PF-07284890 (Part A monotherapy)
    Monotherapy dose escalation of PF-07284890
    Intervention: Drug: PF-07284890
  • Experimental: PF-07284890+binimetinib (Part A combo-therapy)
    Combination dose escalation of PF-07284890 + binimetinib
    Interventions:
    • Drug: PF-07284890
    • Drug: Binimetinib
  • Experimental: Expansion Phase (Part B, Cohort 1)
    PF-07284890 (at recommended dose from Part A) plus binimetinib in participants with BRAF V600 melanoma or Non-Small Cell Lung Cancer (NSCLC), with asymptomatic brain involvement, and no prior BRAF or MEK inhibitor utilization
    Interventions:
    • Drug: PF-07284890
    • Drug: Binimetinib
  • Experimental: Expansion Phase (Part B, Cohort 2)
    PF-07284890 (at recommended dose from Part A) plus binimetinib in participants with BRAF V600 melanoma or NSCLC, with symptomatic brain involvement, and no prior BRAF or MEK inhibitor utilization
    Interventions:
    • Drug: PF-07284890
    • Drug: Binimetinib
  • Experimental: Expansion Phase (Part B, Cohort 3)
    PF-07284890 (at recommended dose from Part A) plus binimetinib in participants with BRAF V600 melanoma or NSCLC, with asymptomatic brain involvement, and prior BRAF inhibitor utilization
    Interventions:
    • Drug: PF-07284890
    • Drug: Binimetinib
  • Experimental: Expansion Phase (Part B, Cohort 4)
    PF-07284890 (at recommended dose from Part A) plus binimetinib in participants with BRAF V600 melanoma or NSCLC, with symptomatic brain involvement, and prior BRAF inhibitor utilization
    Interventions:
    • Drug: PF-07284890
    • Drug: Binimetinib
  • 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
    Interventions:
    • Drug: PF-07284890
    • Drug: Binimetinib
  • Experimental: Drug-Drug Interaction Substudy
    PF-07284890 (at recommended dose from Part A) plus binimetinib plus midazolam in participants with BRAF V600 solid tumor
    Interventions:
    • Drug: PF-07284890
    • Drug: Binimetinib
    • Drug: Midazolam
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 2, 2020)
225
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 30, 2023
Estimated Primary Completion Date September 30, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04543188
Other Study ID Numbers  ICMJE C4471001
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
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.
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP