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
BRAFi Next Generation
PF-07799933, ARRY-440 is an investigational compound. Its safety and efficacy have not been established.
A PHASE 1, OPEN-LABEL, DOSE ESCALATION AND DOSE EXPANSION STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND ANTI TUMOR ACTIVITY OF PF-07799933 (ARRY-440) AS A SINGLE AGENT AND IN COMBINATION THERAPY IN PARTICIPANTS 16 YEARS AND OLDER WITH ADVANCED SOLID TUMORS WITH BRAF ALTERATIONS
Phase 1
NCT05355701
Active enrolling
Locations
United States, Canada, Israel
Study design
Participant Group/Arm
EXPERIMENTAL: Monotherapy dose escalation (Part 1)
Participants will receive PF-07799933
Intervention/Treatment
DRUG: PF-07799933
Tablet
Participant Group/Arm
EXPERIMENTAL: Combination dose escalation (Part 2)
Participants will receive PF-07799933 in combination with binimetinib or cetuximab
Intervention/Treatment
DRUG: PF-07799933
Tablet
DRUG: binimetinib
Tablet
BIOLOGICAL: cetuximab
Injection for intravenous use
Participant Group/Arm
EXPERIMENTAL: Dose expansion (Part 3) - Tumor and mutation specific Cohort 1
Participants will receive PF-07799933
Intervention/Treatment
DRUG: PF-07799933
Tablet
Participant Group/Arm
EXPERIMENTAL: Dose expansion (Part 3) - Tumor and mutation specific Cohort 2
Participants will receive PF-07799933
Intervention/Treatment
DRUG: PF-07799933
Tablet
DRUG: binimetinib
Tablet
Key eligibility criteria
Inclusion criteria
This study is seeking participants who meet the following eligibility criteria:
- Diagnosis of advanced/metastatic solid tumor including primary brain tumor.
- Qualifying BRAF alteration (V600 or non-V600 Class II/Class III BRAF alteration), in tumor tissue and/or blood (ie circulating tumor deoxyribonucleic acid \[DNA\], or ctDNA).
- Disease progressed during/following last prior treatment and no satisfactory alternative treatment options (Part 1 and Part 2).
- Tumor specific cohorts (melanoma, colorectal cancer) must have received specific prior approved therapies
Exclusion criteria
- Brain metastasis larger than 4 cm
- Systemic anti-cancer therapy or small molecule therapeutics ongoing at the start of study treatment.
- For participants who may get binimetinib on study, history or current evidence of retinal vein occlusion (RVO) or concurrent neuromuscular disorder associated with elevated creatine kinase (CK)
Key dates
Study start date
- July 2022
Estimated primary completion date
- January 2029
Key endpoints
Primary Outcome Measures
Outcome Measure
Number of participants with dose limiting toxicities (DLTs) (Part 1 and Part 2)
Measure Description
DLTs will be evaluated during the first cycle (21 days) as both a single agent or in combination with binimetinib or cetuximab
Time Frame
Cycle 1 (21 days)
Outcome Measure
Number of participants with treatment-emergent adverse events (AEs) (Part 1 and Part 2)
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 (Part 1 and Part 2)
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 (Part 1 and Part 2)
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
Dose interruptions due to AEs (Part 1 and Part 2)
Measure Description
Incidence of dose interruptions due to AEs
Time Frame
Baseline to 2 years
Outcome Measure
Dose dose modifications due to AEs (Part 1 and Part 2)
Measure Description
Incidence of dose modifications due to AEs
Time Frame
Baseline to 2 years
Outcome Measure
Discontinuations due to AEs (Part 1 and Part 2)
Measure Description
Incidence of discontinuations due to AEs
Time Frame
Baseline to 2 years
Outcome Measure
MTD (Part 1 and Part 2)
Measure Description
Maximum tolerated dose (MTD)
Time Frame
Cycle 1 (21 days)
Outcome Measure
RDE (Part 1 and Part 2)
Measure Description
Recommended dose for expansion (RDE)
Time Frame
Cycle 1 (21 days)
Outcome Measure
Overall response rate (ORR) (Part 3)
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 clinically significant physical exam abnormalities (Part 1 and Part 2)
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
Part 1 and Part 2: ORR
Measure Description
ORR as assessed using the RECIST version 1.1.
Time Frame
Baseline to 2 years
Outcome Measure
Part 1/2/3: Intracranial response
Measure Description
Intracranial response by RECIST version 1.1 (for brain metastases) \& Response Assessment in Neuro-Oncology (RANO) - for primary brain tumors).
Time Frame
Baseline to 2 years
Outcome Measure
Part 1 and Part 2: Duration of response
Measure Description
Duration of response
Time Frame
Baseline to 2 years
Outcome Measure
Part 3: 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
Part 3: 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
Part 3: 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
Part 3: Dose interruptions due to AEs
Measure Description
Incidence of dose interruptions due to AEs
Time Frame
Baseline to 2 years
Outcome Measure
Part 3: Dose dose modifications due to AEs
Measure Description
Incidence of dose modifications due to AEs
Time Frame
Baseline to 2 years
Outcome Measure
Part 3: Discontinuations due to AEs
Measure Description
Incidence of discontinuations due to AEs
Time Frame
Baseline to 2 years
Outcome Measure
Part 3: Time to event endpoints in each combination
Measure Description
Time to event endpoints in each combination
Time Frame
Baseline to 2 years
Outcome Measure
Part 3: Disease Control Rate (DCR)
Measure Description
DCR
Time Frame
Baseline to 2 years
Outcome Measure
Part 1/2/3: 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
Part 1/2/3: 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
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)
Measure Description
PK parameters of PF-07799933, Single dose, AUClast
Time Frame
Baseline to 2 years
Outcome Measure
Part 1/2/3: PK parameters of PF-07799933, Single dose, area under plasma concentration-time curve over 24 hours (AUC24)
Measure Description
PK parameters of PF-07799933, Single dose, AUC24
Time Frame
Baseline to 2 years
Outcome Measure
Part 1/2/3: PK parameters of PF-07799933, Single dose, area under plasma concentration-time curve over 48 hours (AUC48)
Measure Description
PK parameters of PF-07799933, Single dose, AUC48
Time Frame
Baseline to 2 years
Outcome Measure
Part 1/2/3: 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
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)
Measure Description
PK parameters of PF-07799933, Single dose, AUCinf
Time Frame
Baseline to 2 years
Outcome Measure
Part 1/2/3: 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
Part 1/2/3: 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
Part 1/2/3: 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
Part 1/2/3: PK parameters of PF-07799933, Multiple dose, trough plasma or serum concentration (Ctrough)
Measure Description
PK parameters of PF-07799933, Multiple dose, Ctrough
Time Frame
Baseline to 2 years
Outcome Measure
Part 1/2/3: 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
Part 1/2/3: 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
Part 1/2/3: PK parameters of PF-07799933, Multiple dose, CL/F
Measure Description
PK parameters of PF-07799933, Multiple dose, CL/F
Time Frame
Baseline to 2 years
Outcome Measure
Part 1/2/3: PK parameters of PF-07799933, Multiple dose, average plasma concentration (Cav)
Measure Description
PK parameters of PF-07799933, Multiple dose, Cav
Time Frame
Baseline to 2 years
Outcome Measure
Part 1/2/3: PK parameters of PF-07799933, Multiple dose, peak-to-trough ratio (PTR)
Measure Description
PK parameters of PF-07799933, Multiple dose, PTR
Time Frame
Baseline to 2 years
Outcome Measure
Part 1/2/3: PK parameters of PF-07799933, Multiple dose, accumulation ratio (Rac)
Measure Description
PK parameters of PF-07799933, Multiple dose, Rac (AUCτ /AUCsd,τ)
Time Frame
Baseline to 2 years
Outcome Measure
Part 1/2/3: PK parameters of PF-07799933, Multiple dose, t1/2
Measure Description
PK parameters of PF-07799933, Multiple dose, t1/2
Time Frame
Baseline to 2 years
Outcome Measure
Part 1/2/3: PK parameters of PF-07799933, Multiple dose, Vz/F
Measure Description
PK parameters of PF-07799933, Multiple dose, Vz/F
Time Frame
Baseline to 2 years
Outcome Measure
Part 3: PK parameters of cytochrome P450 (CYP)3A4 probe substrate midazolam, Cmax
Measure Description
PK parameters of CYP3A4 probe substrate midazolam, Cmax
Time Frame
Baseline to 2 years
Outcome Measure
Part 3: PK parameters of CYP3A4 probe substrate midazolam, Tmax
Measure Description
PK parameters of CYP3A4 probe substrate midazolam, Tmax
Time Frame
Baseline to 2 years
Outcome Measure
Part 3: PK parameters of CYP3A4 probe substrate midazolam, AUClast
Measure Description
PK parameters of CYP3A4 probe substrate midazolam, AUClast
Time Frame
Baseline to 2 years
Outcome Measure
Part 3: PK parameters of CYP3A4 probe substrate midazolam, t½
Measure Description
PK parameters of CYP3A4 probe substrate midazolam, t½
Time Frame
Baseline to 2 years
Outcome Measure
Part 3: PK parameters of CYP3A4 probe substrate midazolam, AUCinf
Measure Description
PK parameters of CYP3A4 probe substrate midazolam, AUCinf
Time Frame
Baseline to 2 years
Outcome Measure
Part 3: PK parameters of CYP3A4 probe substrate midazolam, CL/F
Measure Description
PK parameters of CYP3A4 probe substrate midazolam, CL/F
Time Frame
Baseline to 2 years
Outcome Measure
Part 3: PK parameters of CYP3A4 probe substrate midazolam, Vz/F
Measure Description
PK parameters of CYP3A4 probe substrate midazolam, Vz/F
Time Frame
Baseline to 2 years
Outcome Measure
Part 3: TTR
Measure Description
Time to response (TTR)
Time Frame
Baseline to 2 years
Outcome Measure
Part 3: DOR
Measure Description
Duration of response (DOR)
Time Frame
Baseline to 2 years
Outcome Measure
Part 3: PFS
Measure Description
Progression-free survival (PFS)
Time Frame
Baseline to 2 years
Outcome Measure
Part 3: OS
Measure Description
Overall survival (OS)
Time Frame
Baseline to 2 years
Outcome Measure
Number of participants with clinically significant physical exam abnormalities (Part 3)
Measure Description
Physical exam abnormalities as as graded by NCI CTCAE version 5.0
Time Frame
Baseline to 28 days after last dose of study medication
Number of participants
156
Collaborators and investigators
Sponsor: Pfizer
Collaborator: None