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NCT05355701PHASE1Recruiting

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

Pfizer

Start Date

7/5/2022

Completion Date

10/25/2029

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.

Eligibility Criteria

Age Range: 16 years to No maximum

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).

Interventions

DRUG

PF-07799933

DRUG

binimetinib

BIOLOGICAL

cetuximab

DRUG

midazolam

DRUG

fluorouracil

DRUG

leucovorin

DRUG

oxaliplatin

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Conditions

MelanomaNon-Small-Cell Lung CancerThyroid CancerGliomaAdvanced Colorectal Cancer (Part 1)

Locations

Highlands Oncology Group, PA

Fayetteville, Arkansas 72703

United States

Highlands Oncology Group, PA

Rogers, Arkansas 72758

United States

Highlands Oncology Group, PA

Springdale, Arkansas 72762

United States

Clinical and Translational Research Center (CTRC)

Aurora, Colorado 80045

United States

UCHealth Sue Anschutz-Rodgers Eye Center

Aurora, Colorado 80045

United States

University of Colorado Hospital - Anschutz Cancer Pavilion (ACP)

Aurora, Colorado 80045

United States

University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP)

Aurora, Colorado 80045

United States

University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP)

Aurora, Colorado 80045

United States

Sylvester Comprehensive Cancer Center

Miami, Florida 33136

United States

University of Miami Hospital and Clinics

Miami, Florida 33136

United States

Brigham and Women's Hospital

Boston, Massachusetts 02115

United States

Dana-Farber Cancer Institute

Boston, Massachusetts 02215

United States

Dana-Farber Cancer Institute - Chestnut Hill

Newton, Massachusetts 02467

United States

Brigitte Harris Cancer Pavilion

Detroit, Michigan 48202

United States

Henry Ford Cancer - Detroit (Brigitte Harris Cancer Pavilion)

Detroit, Michigan 48202

United States

Henry Ford Medical Center - Columbus

Novi, Michigan 48377

United States

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

Plymouth, Michigan 48170

United States

MSK Monmouth

Middletown, New Jersey 07748

United States

MSK David H. Koch Center for Cancer Care

New York, New York 10021

United States

Memorial Sloan Kettering Cancer Center 53rd street

New York, New York 10022

United States

Memorial Sloan Kettering Cancer Center

New York, New York 10065

United States

Cleveland Clinic Taussig Cancer Center Investigational Pharmacy

Cleveland, Ohio 44106

United States

Cleveland Clinic

Cleveland, Ohio 44195

United States

Providence Cancer Institute Franz Clinic

Portland, Oregon 97213

United States

Providence Portland Medical Center

Portland, Oregon 97213

United States

Sarah Cannon Research Institute - Pharmacy

Nashville, Tennessee 37203

United States

SCRI Oncology Partners

Nashville, Tennessee 37203

United States

TriStar Bone Marrow Transplant

Nashville, Tennessee 37203

United States

TriStar Centennial Medical Center - Cell Processing Lab

Nashville, Tennessee 37203

United States

TriStar Centennial Medical center

Nashville, Tennessee 37203

United States

START San Antonio

San Antonio, Texas 78229

United States

The Ottawa Hospital - General Campus

Ottawa, Ontario K1H 8L6

Canada

Princess Margaret Cancer Centre

Toronto, Ontario M5G 1X6

Canada

University Health Network

Toronto, Ontario M5G 2C4

Canada

Jewish General Hospital

Montreal, Quebec H3T 1E2

Canada

McGill University Health Centre

Montreal, Quebec H4A 3J1

Canada

Sourasky Medical Center

Tel Aviv, Central District 6423906

Israel

Hadassah Medical Center

Jerusalem, 9112001

Israel

Sheba Medical Center

Ramat Gan, 5262000

Israel

Rambam Health Care Campus

Haifa, Ḥeifā 3109601

Israel