The safety and efficacy of this agent(s), or use in this setting, has not been established or is subject to confirmation. For an agent(s) whose safety and efficacy has not been established or confirmed, future regulatory approval or commercial availability is not guaranteed.

Clinical Trial Details

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Other or Multiple Cancer Types

MEK Brain Penetrant Inhibitor

PF-07799544/ARRY-134 is an investigational compound. Its safety and efficacy have not been established.

A PHASE 1A/B OPEN-LABEL MASTER STUDY OF PF-07799544 AS A SINGLE-AGENT AND IN COMBINATION WITH OTHER TARGETED AGENTS IN PARTICIPANTS WITH ADVANCED SOLID TUMORS
Phase 1
NCT05538130

Active enrolling

Globe
Locations

United States, Canada

Study design

Participant Group/Arm

EXPERIMENTAL: Monotherapy Dose Escalation (Phase 1a)

Participants will receive PF-07799544

Intervention/Treatment

DRUG: PF-07799544

Tablet

DRUG: encorafenib

Capsule

Participant Group/Arm

EXPERIMENTAL: Phase 1b Substudy B Combination Dose Escalation

Participants will receive PF-07799544 and PF-07799933

Intervention/Treatment

DRUG: PF-07799544

Tablet

DRUG: PF-07799933

Tablet

Participant Group/Arm

EXPERIMENTAL: Phase 1b Substudy B Combination Dose Expansion

Participants will receive PF-07799544 and PF-07799933

Intervention/Treatment

DRUG: PF-07799544

Tablet

DRUG: PF-07799933

Tablet

Participant Group/Arm

EXPERIMENTAL: Phase 1b Substudy C Combination Dose Expansion

Participants will receive PF-07799544 and PF-07799933

Intervention/Treatment

DRUG: PF-07799544

Tablet

DRUG: PF-07799933

Tablet

Key eligibility criteria

Inclusion criteria
  • Diagnosis of advanced/metastatic solid tumor including primary brain tumor for monotherapy phase 1a dose escalation
  • Disease progressed during/following last prior treatment and no satisfactory alternative treatment options for monotherapy phase 1a dose escalation
  • For Substudy B, histological or cytological diagnosis of advanced/metastatic melanoma
  • For Substudy C, unresectable or adv/metastatic solid tumor progressed on, or with demonstrated intolerance to SOC, excluding melanoma,
  • For Substudy B and C, measurable disease by RECIST version 1.1
  • For Substudy B, evidence of a BRAF V600 mutation or BRAF Class II/III alteration in tumor tissue and/or blood
  • For Substudy C, evidence of a BRAF founder alteration (non-V600 Class II/III BRAF alteration)
Exclusion criteria
  • Brain metastasis larger than 4 cm
  • History or current evidence of retinal vein occlusion (RVO) or concurrent neuromuscular disorder associated with elevated creatine kinase (CK)

Key dates

Study start date
  • November 2022
Estimated primary completion date
  • March 2027

Key endpoints

Primary Outcome Measures
Outcome Measure

Number of participants with dose limiting toxicities (DLTs) Phase 1a monotherapy and Phase 1b combination therapy dose escalation

Measure Description

DLTs will be evaluated during the first cycle (21 days) as a single agent (phase 1a monotherapy) or in combination with other agents (phase 1b dose escalation)

Time Frame

Cycle 1 (21 days)

Outcome Measure

Overall response rate (ORR) (phase 1b expansion)

Measure Description

Response will be evaluated via radiographical tumor assessments by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)

Time Frame

Baseline to 2 years

Outcome Measure

Number of participants with treatment-emergent adverse events (AEs) (phase 1a and 1b dose escalation phases)

Measure Description

AEs as characterized by type, frequency, severity, timing, seriousness, and relationship to study therapy

Time Frame

Baseline to 28 days after last dose of study medication

Outcome Measure

Number of participants with clinically significant change from baseline in laboratory abnormalities (phase 1a and phase 1b dose escalation phase)

Measure Description

Laboratory abnormalities as characterized by type, frequency, severity, and timing.

Time Frame

Baseline to 28 days after last dose of study treatment

Outcome Measure

Number of participants with clinically significant change from baseline in vital sign abnormalities (phase 1a and phase 1b dose escalation phase)

Measure Description

Vital sign abnormalities as characterized by type, frequency, severity, and timing.

Time Frame

Baseline to 28 days after last dose of study treatment

Outcome Measure

Number of participants with clinically significant change from baseline in physical exam abnormalities (phase 1a and phase 1b dose escalation phase)

Measure Description

Physical exam abnormalities as as graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Time Frame

Baseline to 28 days after last dose of study treatment

Secondary Outcome Measures:
Outcome Measure

Number of participants with treatment-emergent adverse events (AEs)

Measure Description

AEs as characterized by type, frequency, severity, timing, seriousness, and relationship to study therapy

Time Frame

Baseline to 2 years

Outcome Measure

Number of participants with clinically significant change from baseline in laboratory abnormalities

Measure Description

Laboratory abnormalities as characterized by type, frequency, severity, and timing.

Time Frame

Baseline to 2 years

Outcome Measure

Number of participants with clinically significant change from baseline in vital sign abnormalities

Measure Description

Vital sign abnormalities as characterized by type, frequency, severity, and timing.

Time Frame

Baseline to 2 years

Outcome Measure

PK parameters of PF-07799544, Single dose, maximum observed concentration (Cmax)

Measure Description

PK parameters of PF-07799544, Single dose, Cmax

Time Frame

Baseline to 2 years

Outcome Measure

PK parameters of PF-07799544, Single dose, time to maximum plasma concentration (Tmax)

Measure Description

PK parameters of PF-07799544, Single dose, Tmax

Time Frame

Baseline to 2 years

Outcome Measure

PK parameters of PF-07799544, Single dose, area under the plasma concentration-time curve from time 0 to the last time point of quantifiable concentration (AUClast)

Measure Description

PK parameters of PF-07799544, Single dose, AUClast

Time Frame

Baseline to 2 years

Outcome Measure

PK parameters of PF-07799544, Single dose, area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUCinf)

Measure Description

PK parameters of PF-07799544, Single dose, AUCinf

Time Frame

Baseline to 2 years

Outcome Measure

PK parameters of PF-07799544, Single dose, terminal elimination half life (t½)

Measure Description

PK parameters of PF-07799544, Single dose, t½

Time Frame

Baseline to 2 years

Outcome Measure

PK parameters of PF-07799544, Single dose, apparent oral clearance (CL/F)

Measure Description

PK parameters of PF-07799544, Single dose, CL/F

Time Frame

Baseline to 2 years

Outcome Measure

PK parameters of PF-07799544, Single dose, apparent volume of distribution (Vz/F)

Measure Description

PK parameters of PF-07799544, Single dose, Vz/F

Time Frame

Baseline to 2 years

Outcome Measure

PK parameters of PF-07799544, Multiple dose, maximum observed concentration (Cmax)

Measure Description

PK parameters of PF-07799544, Multiple dose, Cmax

Time Frame

Baseline to 2 years

Outcome Measure

PK parameters of PF-07799544, Multiple dose, time to maximum plasma concentration (Tmax)

Measure Description

PK parameters of PF-07799544, Multiple dose, Tmax

Time Frame

Baseline to 2 years

Outcome Measure

PK parameters of PF-07799544, Multiple dose, area under the plasma concentration-time curve over the dosing interval (AUCτ)

Measure Description

PK parameters of PF-07799544, Multiple dose, AUCτ

Time Frame

Baseline to 2 years

Outcome Measure

PK parameters of PF-07799544, Multiple dose, terminal elimination half life (t½)

Measure Description

PK parameters of PF-07799544, Multiple dose, t½

Time Frame

Baseline to 2 years

Outcome Measure

PK parameters of PF-07799544, Multiple dose, apparent oral clearance (CL/F)

Measure Description

PK parameters of PF-07799544, Multiple dose, CL/F

Time Frame

Baseline to 2 years

Outcome Measure

PK parameters of PF-07799544, Multiple dose, apparent volume of distribution (Vz/F)

Measure Description

PK parameters of PF-07799544, Multiple dose, Vz/F

Time Frame

Baseline to 2 years

Outcome Measure

PK parameters of PF-07799933, Single dose, maximum observed concentration (Cmax)

Measure Description

PK parameters of PF-07799933, Single dose, Cmax

Time Frame

Baseline to 2 years

Outcome Measure

PK parameters of PF-07799933, Single dose, time to maximum plasma concentration (Tmax)

Measure Description

PK parameters of PF-07799933, Single dose, Tmax

Time Frame

Baseline to 2 years

Outcome Measure

PK parameters of PF-07799933, Single dose, area under the plasma concentration-time curve from time 0 to the last time point of quantifiable concentration (AUClast)

Measure Description

PK parameters of PF-07799933, Single dose, AUClast

Time Frame

Baseline to 2 years

Outcome Measure

PK parameters of PF-07799933, Single dose, area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUCinf)

Measure Description

PK parameters of PF-07799933, Single dose, AUCinf

Time Frame

Baseline to 2 years

Outcome Measure

PK parameters of PF-07799933, Single dose, terminal elimination half life (t½)

Measure Description

PK parameters of PF-07799933, Single dose, t½

Time Frame

Baseline to 2 years

Outcome Measure

PK parameters of PF-07799933, Single dose, apparent oral clearance (CL/F)

Measure Description

PK parameters of PF-07799933, Single dose, CL/F

Time Frame

Baseline to 2 years

Outcome Measure

PK parameters of PF-07799933, Single dose, apparent volume of distribution (Vz/F)

Measure Description

PK parameters of PF-07799933, Single dose, Vz/F

Time Frame

Baseline to 2 years

Outcome Measure

PK parameters of PF-07799933, Multiple dose, maximum observed concentration (Cmax)

Measure Description

PK parameters of PF-07799933, Multiple dose, Cmax

Time Frame

Baseline to 2 years

Outcome Measure

PK parameters of PF-07799933, Multiple dose, time to maximum plasma concentration (Tmax)

Measure Description

PK parameters of PF-07799933, Multiple dose, Tmax

Time Frame

Baseline to 2 years

Outcome Measure

PK parameters of PF-07799933, Multiple dose, area under the plasma concentration-time curve over the dosing interval (AUCτ)

Measure Description

PK parameters of PF-07799933, Multiple dose, AUCτ

Time Frame

Baseline to 2 years

Outcome Measure

PK parameters of PF-07799933, Multiple dose, terminal elimination half life (t½)

Measure Description

PK parameters of PF-07799933, Multiple dose, t½

Time Frame

Baseline to 2 years

Outcome Measure

PK parameters of PF-07799933, Multiple dose, apparent oral clearance (CL/F)

Measure Description

PK parameters of PF-07799933, Multiple dose, CL/F

Time Frame

Baseline to 2 years

Outcome Measure

PK parameters of PF-07799933, Multiple dose, apparent volume of distribution (Vz/F)

Measure Description

PK parameters of PF-07799933, Multiple dose, Vz/F

Time Frame

Baseline to 2 years

Outcome Measure

ORR (phase 1a and phase 1b dose escalation)

Measure Description

ORR as assessed using the RECIST version 1.1.

Time Frame

Baseline to 2 years

Outcome Measure

Duration of response overall and in CNS

Time Frame

Baseline to 2 years

Outcome Measure

Intracranial response (phase 1b Part 2)

Measure Description

Intracranial response by RECIST version 1.1 (for brain metastases)

Time Frame

Baseline to 2 years

Outcome Measure

PFS

Time Frame

Baseline to 2 years

Number of participants

124

Collaborators and investigators

Sponsor: Pfizer

Collaborator: None

This information is current as of March 26th 2024.