The purpose of this clinical trial is to learn the safety and effects of the study medicine (PF-07799544) alone or in combination as a potential cancer treatment for adults with advanced solid tumors. The study will be conducted in two parts: PF-07799544 as a single agent (Phase 1a) and PF-07799544 in combination with another study medicine called PF-07799933 (Phase 1b).
Phase 1a is no longer open for enrollment. In Phase1b (noted as "this study"), we are seeking participants who have:
* a solid tumor which is metastatic or recurrent (excluding colorectal cancer) * tumor with the mutation (abnormal gene) called "BRAF V600" * received required prior treatment for cancer per cohort assigned.
All participants in this study will receive both study medicines. Both study medicines are tablets that are taken by mouth at home twice a day.
Participants will receive study medicines until their cancer is no longer responding, unacceptable side effects, or 2 years. Participants may continue to receive study therapy beyond 2 years. We will examine the experiences of people receiving the study medicines. This will help us determine if the study medicines are safe and effective.
Diagnosis of advanced/metastatic solid tumor (excluding colorectal cancer)
Measurable disease by RECIST version 1.1
Evidence of a BRAF V600 mutation
Prior therapy per tumor cohort
Other active malignancy within 3 years
Presence of leptomeningeal disease
History or current evidence of retinal vein occlusion (RVO) or history of retinal degenerative disease
Concurrent neuromuscular disorder associated with elevated creatine kinase (CK)
Sequential
PF-07799544
DrugTablet
PF-07799933
DrugTablet
Phase 1a monotherapy and Phase 1b combination dose escalation: Number of participants with dose limiting toxicities (DLTs)
DLTs will be evaluated during the first cycle (21 days) as a single agent (phase 1a monotherapy) or in combination with other agents (phase 1b dose escalation)
Phase 1a monotherapy and Phase 1b combination dose escalation: Number of participants with treatment-emergent adverse events (AEs)
AEs as characterized by type, frequency, severity, timing, seriousness, and relationship to study therapy
Phase 1a monotherapy and Phase 1b combination dose escalation: Number of participants with clinically significant change from baseline in laboratory abnormalities
Laboratory abnormalities as characterized by type, frequency, severity, and timing.
Phase 1a monotherapy and Phase 1b combination dose escalation: Number of participants with clinically significant change from baseline in vital sign abnormalities
Vital sign abnormalities as characterized by type, frequency, severity, and timing.
Phase 1a monotherapy and Phase 1b combination dose escalation: ORR
ORR as assessed using the RECIST version 1.1.
Phase 1b Dose Expansion: Number of participants with treatment-emergent adverse events (AEs)
AEs as characterized by type, frequency, severity, timing, seriousness, and relationship to study therapy
Phase 1b Dose Expansion: Number of participants with clinically significant change from baseline in vital sign abnormalities
Vital sign abnormalities as characterized by type, frequency, severity, and timing.
Phase 1b Dose Expansion: Number of participants with clinically significant change from baseline in laboratory abnormalities
Laboratory abnormalities as characterized by type, frequency, severity, and timing.
