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 (called binimetinib) 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. 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
This study is seeking participants who meet the following 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 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)