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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.
PF-07799933, ARRY-440 is an investigational compound. Its safety and efficacy have not been established.
Active enrolling
United States, Canada, Israel
EXPERIMENTAL: Monotherapy dose escalation (Part 1)
Participants will receive PF-07799933
DRUG: PF-07799933
TabletEXPERIMENTAL: Combination dose escalation (Part 2)
Participants will receive PF-07799933 in combination with binimetinib or cetuximab
DRUG: PF-07799933
TabletDRUG: binimetinib
TabletBIOLOGICAL: cetuximab
Injection for intravenous useEXPERIMENTAL: Dose expansion (Part 3) - Tumor and mutation specific Cohort 1
Participants will receive PF-07799933
DRUG: PF-07799933
TabletEXPERIMENTAL: Dose expansion (Part 3) - Tumor and mutation specific Cohort 2
Participants will receive PF-07799933
DRUG: PF-07799933
TabletDRUG: binimetinib
TabletNumber of participants with dose limiting toxicities (DLTs) (Part 1 and Part 2)
DLTs will be evaluated during the first cycle (21 days) as both a single agent or in combination with binimetinib or cetuximab
Cycle 1 (21 days)
Number of participants with treatment-emergent adverse events (AEs) (Part 1 and Part 2)
AEs as characterized by type, frequency, severity, timing, seriousness, and relationship to study therapy
Baseline to 28 days after last dose of study medication
Number of participants with clinically significant change from baseline in laboratory abnormalities (Part 1 and Part 2)
Laboratory abnormalities as characterized by type, frequency, severity, and timing
Baseline to 28 days after last dose of study treatment
Number of participants with clinically significant change from baseline in vital sign abnormalities (Part 1 and Part 2)
Vital sign abnormalities as characterized by type, frequency, severity, and timing
Baseline to 28 days after last dose of study treatment
Dose interruptions due to AEs (Part 1 and Part 2)
Incidence of dose interruptions due to AEs
Baseline to 2 years
Dose dose modifications due to AEs (Part 1 and Part 2)
Incidence of dose modifications due to AEs
Baseline to 2 years
Discontinuations due to AEs (Part 1 and Part 2)
Incidence of discontinuations due to AEs
Baseline to 2 years
MTD (Part 1 and Part 2)
Maximum tolerated dose (MTD)
Cycle 1 (21 days)
RDE (Part 1 and Part 2)
Recommended dose for expansion (RDE)
Cycle 1 (21 days)
Overall response rate (ORR) (Part 3)
Response will be evaluated via radiographical tumor assessments by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
Baseline to 2 years
Number of participants with clinically significant physical exam abnormalities (Part 1 and Part 2)
Physical exam abnormalities as as graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Baseline to 28 days after last dose of study treatment
Part 1 and Part 2: ORR
ORR as assessed using the RECIST version 1.1.
Baseline to 2 years
Part 1/2/3: Intracranial response
Intracranial response by RECIST version 1.1 (for brain metastases) \& Response Assessment in Neuro-Oncology (RANO) - for primary brain tumors).
Baseline to 2 years
Part 1 and Part 2: Duration of response
Duration of response
Baseline to 2 years
Part 3: Number of participants with treatment-emergent adverse events (AEs)
AEs as characterized by type, frequency, severity, timing, seriousness, and relationship to study therapy
Baseline to 2 years
Part 3: Number of participants with clinically significant change from baseline in laboratory abnormalities
Laboratory abnormalities as characterized by type, frequency, severity, and timing
Baseline to 2 years
Part 3: Number of participants with clinically significant change from baseline in vital sign abnormalities
Vital sign abnormalities as characterized by type, frequency, severity, and timing
Baseline to 2 years
Part 3: Dose interruptions due to AEs
Incidence of dose interruptions due to AEs
Baseline to 2 years
Part 3: Dose dose modifications due to AEs
Incidence of dose modifications due to AEs
Baseline to 2 years
Part 3: Discontinuations due to AEs
Incidence of discontinuations due to AEs
Baseline to 2 years
Part 3: Time to event endpoints in each combination
Time to event endpoints in each combination
Baseline to 2 years
Part 3: Disease Control Rate (DCR)
DCR
Baseline to 2 years
Part 1/2/3: PK parameters of PF-07799933, Single dose, maximum observed concentration (Cmax)
PK parameters of PF-07799933, Single dose, Cmax
Baseline to 2 years
Part 1/2/3: PK parameters of PF-07799933, Single dose, time to maximum plasma concentration (Tmax)
PK parameters of PF-07799933, Single dose, Tmax
Baseline to 2 years
Part 1/2/3: 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)
PK parameters of PF-07799933, Single dose, AUClast
Baseline to 2 years
Part 1/2/3: PK parameters of PF-07799933, Single dose, area under plasma concentration-time curve over 24 hours (AUC24)
PK parameters of PF-07799933, Single dose, AUC24
Baseline to 2 years
Part 1/2/3: PK parameters of PF-07799933, Single dose, area under plasma concentration-time curve over 48 hours (AUC48)
PK parameters of PF-07799933, Single dose, AUC48
Baseline to 2 years
Part 1/2/3: PK parameters of PF-07799933, Single dose, terminal elimination half life (t½)
PK parameters of PF-07799933, Single dose, t½
Baseline to 2 years
Part 1/2/3: PK parameters of PF-07799933, Single dose, area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUCinf)
PK parameters of PF-07799933, Single dose, AUCinf
Baseline to 2 years
Part 1/2/3: PK parameters of PF-07799933, Single dose, apparent oral clearance (CL/F)
PK parameters of PF-07799933, Single dose, CL/F
Baseline to 2 years
Part 1/2/3: PK parameters of PF-07799933, Single dose, apparent volume of distribution (Vz/F)
PK parameters of PF-07799933, Single dose, Vz/F
Baseline to 2 years
Part 1/2/3: PK parameters of PF-07799933, Multiple dose, maximum observed concentration (Cmax)
PK parameters of PF-07799933, Multiple dose, Cmax
Baseline to 2 years
Part 1/2/3: PK parameters of PF-07799933, Multiple dose, trough plasma or serum concentration (Ctrough)
PK parameters of PF-07799933, Multiple dose, Ctrough
Baseline to 2 years
Part 1/2/3: PK parameters of PF-07799933, Multiple dose, time to maximum plasma concentration (Tmax)
PK parameters of PF-07799933, Multiple dose, Tmax
Baseline to 2 years
Part 1/2/3: PK parameters of PF-07799933, Multiple dose, area under the plasma concentration-time curve over the dosing interval (AUCτ)
PK parameters of PF-07799933, Multiple dose, AUCτ
Baseline to 2 years
Part 1/2/3: PK parameters of PF-07799933, Multiple dose, CL/F
PK parameters of PF-07799933, Multiple dose, CL/F
Baseline to 2 years
Part 1/2/3: PK parameters of PF-07799933, Multiple dose, average plasma concentration (Cav)
PK parameters of PF-07799933, Multiple dose, Cav
Baseline to 2 years
Part 1/2/3: PK parameters of PF-07799933, Multiple dose, peak-to-trough ratio (PTR)
PK parameters of PF-07799933, Multiple dose, PTR
Baseline to 2 years
Part 1/2/3: PK parameters of PF-07799933, Multiple dose, accumulation ratio (Rac)
PK parameters of PF-07799933, Multiple dose, Rac (AUCτ /AUCsd,τ)
Baseline to 2 years
Part 1/2/3: PK parameters of PF-07799933, Multiple dose, t1/2
PK parameters of PF-07799933, Multiple dose, t1/2
Baseline to 2 years
Part 1/2/3: PK parameters of PF-07799933, Multiple dose, Vz/F
PK parameters of PF-07799933, Multiple dose, Vz/F
Baseline to 2 years
Part 3: PK parameters of cytochrome P450 (CYP)3A4 probe substrate midazolam, Cmax
PK parameters of CYP3A4 probe substrate midazolam, Cmax
Baseline to 2 years
Part 3: PK parameters of CYP3A4 probe substrate midazolam, Tmax
PK parameters of CYP3A4 probe substrate midazolam, Tmax
Baseline to 2 years
Part 3: PK parameters of CYP3A4 probe substrate midazolam, AUClast
PK parameters of CYP3A4 probe substrate midazolam, AUClast
Baseline to 2 years
Part 3: PK parameters of CYP3A4 probe substrate midazolam, t½
PK parameters of CYP3A4 probe substrate midazolam, t½
Baseline to 2 years
Part 3: PK parameters of CYP3A4 probe substrate midazolam, AUCinf
PK parameters of CYP3A4 probe substrate midazolam, AUCinf
Baseline to 2 years
Part 3: PK parameters of CYP3A4 probe substrate midazolam, CL/F
PK parameters of CYP3A4 probe substrate midazolam, CL/F
Baseline to 2 years
Part 3: PK parameters of CYP3A4 probe substrate midazolam, Vz/F
PK parameters of CYP3A4 probe substrate midazolam, Vz/F
Baseline to 2 years
Part 3: TTR
Time to response (TTR)
Baseline to 2 years
Part 3: DOR
Duration of response (DOR)
Baseline to 2 years
Part 3: PFS
Progression-free survival (PFS)
Baseline to 2 years
Part 3: OS
Overall survival (OS)
Baseline to 2 years
Number of participants with clinically significant physical exam abnormalities (Part 3)
Physical exam abnormalities as as graded by NCI CTCAE version 5.0
Baseline to 28 days after last dose of study medication
156
Sponsor: Pfizer
Collaborator: None
For more information, call or email the Pfizer Clinical Trial Contact Center:
When calling, please reference this study number: