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.

NCT05355701

Geo Regions

Clinical Study Trial ID
NCT05355701
Brief Title
A Study to Learn About the Study Medicine Called PF-07799933 in People With Advanced Solid Tumors With BRAF Alterations.
Study Start Date
Study End Date
Enrollment Count
156
Conditions (Long)
Melanoma, Non-Small-Cell Lung Cancer, Thyroid Cancer, Glioma
Official Title

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

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)
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

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

Sponsor
Pfizer
Data Updated date
Enrollment Status
Phases
Location
United States, Canada, Israel
Study Type
Interventional
Molecule Content