A Study to Learn About the Study Medicine Called PF-07799933 in People With Advanced Solid Tumors With BRAF Alterations.

Phase 1RecruitingNCT05355701

Pfizer267 enrolled

Overview

The purpose of this clinical trial is to learn about the safety and effects of the study medicine (called PF-07799933) administered as a single agent and in combination with other study medicines in people with solid tumors. This study is seeking participants who have an advanced solid tumor with a certain type of abnormal gene called "BRAF" and available treatments are no longer effective in controlling their cancer. All participants in this study will receive PF-07799933. PF-07799933 comes as a tablet to take by mouth, 2 times a day. Depending on the part of the study, participants may also receive another study medicine: * People with melanoma or other solid tumors may also receive binimetinib. Binimetinib comes as a tablet to take by mouth, 2 times a day. * People with colorectal cancer may also receive cetuximab or cetuximab and mFOLFOX6 (Chemotherapy regimen). Cetuximab will be given weekly (or every two weeks) in the clinic as a shot given in the vein or port (intravenous, IV). Participants may receive the study medicines for about 2 years. The study team will monitor how each participant is doing with the study treatment during regular visits at the study clinic.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

267

Conditions

Melanoma Non-Small-Cell Lung Cancer

Interventions

PF-07799933DRUG

Tablet

binimetinibDRUG

Tablet

cetuximabBIOLOGICAL

Injection for intravenous use

midazolamDRUG

syrup

fluorouracilDRUG

Injection for intravenous use

leucovorinDRUG

Injection for intravenous use

oxaliplatinDRUG

Injection for intravenous use

Eligibility

Sex: ALLMin age: 16 Years

Medical Language ↔ Plain English

This study is seeking participants who meet the following key eligibility criteria: Inclusion 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, Part 2 (doublet), and Part 3 (cohorts 2, 3, 6, 7)). * Tumor specific cohorts (melanoma, colorectal cancer) must have received specific prior approved therapies * Part 3 (Cohort 1) (BRAF V600 mutant melanoma): Prior BRAF V600 inhibitor therapy required, prior MEK inhibitor therapy required, and immune checkpoint inhibitor therapy required. * Part 3 (Cohort 4) (BRAF V600E CRC): Minimum of 2 cycles of prior 5-FU based chemotherapy required. No prior BRAF inhibitor/EGFR inhibitor allowed. Participants with MSI-H/dMMR mCRC should receive prior immune checkpoint inhibitor therapy. * Part 3 (Cohort 5) (BRAF V600E CRC): No more than 2 cycles of prior 5-FU based chemotherapy allowed. No prior BRAF inhibitor/EGFR inhibitors allowed. Participants with MSI-H/dMMR mCRC should receive prior immune checkpoint inhibitor therapy. Exclusion Criteria: * Brain metastasis larger than 4 cm * Systemic anti-cancer therapy or small molecule therapeutics ongoing at the start of study treatment. * History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO; history of retinal degenerative disease. * Concurrent neuromuscular disorder associated with elevated creatine kinase (CK).

Locations (41)

Highlands Oncology Group

Fayetteville, Arkansas, United States

RECRUITING

Highlands Oncology Group

Rogers, Arkansas, United States

RECRUITING

Highlands Oncology Group

Springdale, Arkansas, United States

RECRUITING

Clinical and Translational Research Center (CTRC)

Aurora, Colorado, United States

Outcomes

Primary Outcomes

Number 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: Baseline to 2 years

Dose dose modifications due to AEs (Part 1 and Part 2)

Incidence of dose modifications due to AEs

Time frame: Baseline to 2 years

Discontinuations due to AEs (Part 1 and Part 2)

Incidence of discontinuations due to AEs

Time frame: Baseline to 2 years

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)

Time frame: 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

Time frame: Baseline to 28 days after last dose of study treatment

Secondary Outcomes

Part 1 and Part 2: ORR

ORR as assessed using the RECIST version 1.1.

Time frame: 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).

Time frame: Baseline to 2 years

Part 1 and Part 2: Duration of response

Duration of response

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: Baseline to 2 years

Part 3: Dose interruptions due to AEs

Incidence of dose interruptions due to AEs

Time frame: Baseline to 2 years

Part 3: Dose dose modifications due to AEs

Incidence of dose modifications due to AEs

Time frame: Baseline to 2 years

Part 3: Discontinuations due to AEs

Central Contacts

Pfizer CT.gov Call Center

CONTACT

1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

UCHealth Sue Anschutz-Rodgers Eye Center

Aurora, Colorado, United States

RECRUITING

University of Colorado Hospital - Anschutz Cancer Pavilion (ACP)

Aurora, Colorado, United States

RECRUITING

University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP)

Aurora, Colorado, United States

RECRUITING

University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP)

Aurora, Colorado, United States

RECRUITING

Sylvester Comprehensive Cancer Center

Miami, Florida, United States

RECRUITING

University of Miami Hospital and Clinics

Miami, Florida, United States

RECRUITING

...and 31 more locations

Incidence of discontinuations due to AEs

Time frame: Baseline to 2 years

Part 3: Time to event endpoints in each combination

Time to event endpoints in each combination

Time frame: Baseline to 2 years

Part 3: Disease Control Rate (DCR)

DCR

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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)

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: Baseline to 2 years

Part 3: PK parameters of CYP3A4 probe substrate midazolam, Tmax

PK parameters of CYP3A4 probe substrate midazolam, Tmax

Time frame: Baseline to 2 years

Part 3: PK parameters of CYP3A4 probe substrate midazolam, AUClast

PK parameters of CYP3A4 probe substrate midazolam, AUClast

Time frame: Baseline to 2 years

Part 3: PK parameters of CYP3A4 probe substrate midazolam, t½

PK parameters of CYP3A4 probe substrate midazolam, t½

Time frame: Baseline to 2 years

Part 3: PK parameters of CYP3A4 probe substrate midazolam, AUCinf

PK parameters of CYP3A4 probe substrate midazolam, AUCinf

Time frame: Baseline to 2 years

Part 3: PK parameters of CYP3A4 probe substrate midazolam, CL/F

PK parameters of CYP3A4 probe substrate midazolam, CL/F

Time frame: Baseline to 2 years

Part 3: PK parameters of CYP3A4 probe substrate midazolam, Vz/F

PK parameters of CYP3A4 probe substrate midazolam, Vz/F

Time frame: Baseline to 2 years

Part 3: TTR

Time to response (TTR)

Time frame: Baseline to 2 years

Part 3: DOR

Duration of response (DOR)

Time frame: Baseline to 2 years

Part 3: PFS

Progression-free survival (PFS)

Time frame: Baseline to 2 years

Part 3: OS

Overall survival (OS)

Time frame: 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

Time frame: Baseline to 28 days after last dose of study medication