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
Geo Regions
![Category Image](/sites/default/files/2024-05/Other%20Cancer_dark-blue_15.png)
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
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