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

NCT05355701 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: C4761001BRAF Class 2
• Study Type: interventional
• Target: 267
• Locations: 3 countries
• Sites: 40

Brief Summary

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.

Conditions

Melanoma; Non-Small-Cell Lung Cancer; Glioma; Advanced Colorectal Cancer (Part 1); Thyroid Cancer

Outcome Measures

Primary Outcomes (9)

• 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

  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

• 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

Secondary Outcomes (42)

• Part 1 and Part 2: ORR

  Baseline to 2 years

• Part 1/2/3: Intracranial response

  Baseline to 2 years

• Part 1 and Part 2: Duration of response

  Baseline to 2 years

• Part 3: Number of participants with treatment-emergent adverse events (AEs)

  Baseline to 2 years

• Part 3: Number of participants with clinically significant change from baseline in laboratory abnormalities

  Baseline to 2 years

Study Arms (9)

Monotherapy dose escalation (Part 1)

EXPERIMENTAL

Participants will receive PF-07799933

Drug: PF-07799933

Combination dose escalation (Part 2)

EXPERIMENTAL

Participants will receive PF-07799933 in combination with binimetinib or cetuximab

Drug: PF-07799933; Drug: binimetinib; Biological: cetuximab

Dose expansion (Part 3) - Tumor and mutation specific Cohort 1

EXPERIMENTAL

Participants will receive PF-07799933

Drug: PF-07799933

Dose expansion (Part 3) - Tumor and mutation specific Cohort 2

EXPERIMENTAL

Participants will receive PF-07799933

Drug: PF-07799933; Drug: binimetinib

Dose expansion (Part 3) - Tumor and mutation specific Cohort 3

EXPERIMENTAL

Participants will receive PF-07799933

Drug: PF-07799933; Drug: midazolam

Dose expansion (Part 3) - Tumor and mutation specific Cohort 4

EXPERIMENTAL

Participants will receive PF-07799933 in combination with cetuximab

Drug: PF-07799933; Biological: cetuximab

Dose expansion (Part 3) - Tumor and mutation specific Cohort 5

EXPERIMENTAL

Participants will receive PF-07799933 in combination with cetuximab and mFOLFOX6 regimen

Drug: PF-07799933; Biological: cetuximab; Drug: fluorouracil; Drug: leucovorin; Drug: oxaliplatin

Dose expansion (Part 3) - Tumor and mutation specific Cohort 6

EXPERIMENTAL

Participants will receive PF-07799933

Drug: PF-07799933

Dose expansion (Part 3) - Tumor and mutation specific Cohort 7

EXPERIMENTAL

Participants will receive PF-07799933

Drug: PF-07799933

Interventions

binimetinib DRUG

Tablet

Also known as: Mektovi, PF-06811462, MEK162

Combination dose escalation (Part 2); Dose expansion (Part 3) - Tumor and mutation specific Cohort 2

PF-07799933 DRUG

Tablet

Also known as: ARRY-440

Combination dose escalation (Part 2); Dose expansion (Part 3) - Tumor and mutation specific Cohort 1; Dose expansion (Part 3) - Tumor and mutation specific Cohort 2; Dose expansion (Part 3) - Tumor and mutation specific Cohort 3; Dose expansion (Part 3) - Tumor and mutation specific Cohort 4; Dose expansion (Part 3) - Tumor and mutation specific Cohort 5; Dose expansion (Part 3) - Tumor and mutation specific Cohort 6; Dose expansion (Part 3) - Tumor and mutation specific Cohort 7; Monotherapy dose escalation (Part 1)

cetuximab BIOLOGICAL

Injection for intravenous use

Also known as: Erbitux

Combination dose escalation (Part 2); Dose expansion (Part 3) - Tumor and mutation specific Cohort 4; Dose expansion (Part 3) - Tumor and mutation specific Cohort 5

midazolam DRUG

syrup

Dose expansion (Part 3) - Tumor and mutation specific Cohort 3

fluorouracil DRUG

Injection for intravenous use

Dose expansion (Part 3) - Tumor and mutation specific Cohort 5

leucovorin DRUG

Injection for intravenous use

Dose expansion (Part 3) - Tumor and mutation specific Cohort 5

oxaliplatin DRUG

Injection for intravenous use

Dose expansion (Part 3) - Tumor and mutation specific Cohort 5

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Pfizer: lead

Study Sites (40)

Highlands Oncology Group

Fayetteville, Arkansas, 72703, United States

RECRUITING

Highlands Oncology Group

Rogers, Arkansas, 72758, United States

RECRUITING

Highlands Oncology Group

Springdale, Arkansas, 72762, United States

RECRUITING

Clinical and Translational Research Center (CTRC)

Aurora, Colorado, 80045, United States

RECRUITING

UCHealth Sue Anschutz-Rodgers Eye Center

Aurora, Colorado, 80045, United States

RECRUITING

University of Colorado Hospital - Anschutz Cancer Pavilion (ACP)

Aurora, Colorado, 80045, United States

RECRUITING

University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP)

Aurora, Colorado, 80045, United States

RECRUITING

University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP)

Aurora, Colorado, 80045, United States

RECRUITING

Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

RECRUITING

University of Miami Hospital and Clinics

Miami, Florida, 33136, United States

RECRUITING

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

DFCI Chestnut Hill

Newton, Massachusetts, 02459, United States

RECRUITING

Brigitte Harris Cancer Pavilion

Detroit, Michigan, 48202, United States

RECRUITING

Henry Ford Hospital

Detroit, Michigan, 48202, United States

RECRUITING

Henry Ford Medical Center - Columbus

Novi, Michigan, 48377, United States

RECRUITING

CT Scan and Echo Only: Henry Ford Medical Center-Plymouth

Plymouth, Michigan, 48170, United States

RECRUITING

MSK Monmouth

Middletown, New Jersey, 07748, United States

RECRUITING

MSK David H. Koch Center for Cancer Care

New York, New York, 10021, United States

RECRUITING

Memorial Sloan Kettering Cancer Center 53rd street

New York, New York, 10022, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Cleveland Clinic Taussig Cancer Center Investigational Pharmacy

Cleveland, Ohio, 44106, United States

RECRUITING

Cleveland Clinic

Cleveland, Ohio, 44195, United States

RECRUITING

Providence Cancer Institute Franz Clinic

Portland, Oregon, 97213, United States

RECRUITING

Providence Portland Medical Center

Portland, Oregon, 97213, United States

RECRUITING

Sarah Cannon Research Institute - Pharmacy

Nashville, Tennessee, 37203, United States

RECRUITING

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

RECRUITING

TriStar Bone Marrow Transplant

Nashville, Tennessee, 37203, United States

RECRUITING

TriStar Centennial Medical Center - Cell Processing Lab

Nashville, Tennessee, 37203, United States

RECRUITING

TriStar Centennial Medical center

Nashville, Tennessee, 37203, United States

RECRUITING

START San Antonio

San Antonio, Texas, 78229, United States

RECRUITING

The Ottawa Hospital - General Campus

Ottawa, Ontario, K1H 8L6, Canada

RECRUITING

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 1X6, Canada

RECRUITING

University Health Network

Toronto, Ontario, M5G 2C4, Canada

RECRUITING

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

RECRUITING

McGill University Health Centre

Montreal, Quebec, H4A 3J1, Canada

RECRUITING

Sourasky Medical Center

Tel Aviv, Central District, 6423906, Israel

RECRUITING

Hadassah Medical Center

Jerusalem, 9112001, Israel

RECRUITING

Sheba Medical Center

Ramat Gan, 5262000, Israel

RECRUITING

Rambam Health Care Campus

Haifa, Ḥeifā, 3109601, Israel

RECRUITING

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Melanoma; Carcinoma, Non-Small-Cell Lung; Thyroid Neoplasms; Glioma

Interventions

binimetinib; Cetuximab; Midazolam; Fluorouracil; Leucovorin; Oxaliplatin

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases; Neoplasms, Neuroepithelial; Neoplasms, Glandular and Epithelial

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Central Study Contacts

Pfizer CT.gov Call Center

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2022
• First Posted: May 2, 2022
• Study Start: July 5, 2022
• Primary Completion (Estimated): April 23, 2028
• Study Completion (Estimated): October 25, 2029
• Last Updated: June 5, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CA (5); US (31); IL (4)