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

What this study is about

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.

Who can join (things the study team will check)

✅ You may be able to join 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 be able to join 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).

Where this trial is running

• Highlands Oncology Group, Fayetteville, Arkansas, United States
• Highlands Oncology Group, Rogers, Arkansas, United States
• Highlands Oncology Group, Springdale, Arkansas, United States
• Clinical and Translational Research Center (CTRC), Aurora, Colorado, United States
• UCHealth Sue Anschutz-Rodgers Eye Center, Aurora, Colorado, United States
• University of Colorado Hospital - Anschutz Cancer Pavilion (ACP), Aurora, Colorado, United States
• University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP), Aurora, Colorado, United States
• University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP), Aurora, Colorado, United States
• Sylvester Comprehensive Cancer Center, Miami, Florida, United States
• University of Miami Hospital and Clinics, Miami, Florida, United States
• Brigham and Women's Hospital, Boston, Massachusetts, United States
• Dana-Farber Cancer Institute, Boston, Massachusetts, United States

+ 28 more sites.

Who to contact

Pfizer CT.gov Call Center · 1-800-718-1021 · ClinicalTrials.gov_Inquiries@pfizer.com

It's completely normal to call and ask questions before deciding anything. Mention the study ID: NCT05355701.