Advanced or Metastatic Solid Tumors, Brain Neoplasms, Differentiated Thyroid Cancer, Glioma, HGG, High Grade Glioma, LGG, Low Grade Glioma, Malignant Neoplasms, Melanoma, Non-Small Cell Lung Cancer, NSCLC (Non-small Cell Lung Cancer), Thyroid Cancer
Conditions
Keywords
solid tumors, BRAF, advanced solid tumors, B-Raf, MAPK, neoplasms, BRAF V600
Brief summary
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.
Interventions
DRUGPF-07799544
Tablet
DRUGPF-07799933
Tablet
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Phase 1b Inclusion Criteria: * 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 * Adequate organ function per protocol Phase 1b
Exclusion criteria
* 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) * Active gastrointestinal disease as defined per protocol * History of interstitial lung disease as defined per protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1a monotherapy and Phase 1b combination dose escalation: Number of participants with dose limiting toxicities (DLTs) | Cycle 1 (21 days) | 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) | Baseline to 28 days after last dose of study medication | 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 | Baseline to 28 days after last dose of study treatment | 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 | Baseline to 28 days after last dose of study treatment | Vital sign 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 physical exam abnormalities | Baseline to 28 days after last dose of study treatment | Physical exam abnormalities as as graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. |
| Phase 1b Dose Expansion: Overall response rate (ORR) | Baseline to 2 years | Response will be evaluated via radiographical tumor assessments by RECIST v1.1 for solid tumors or RANO for primary brain tumors |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1a monotherapy and Phase 1b combination dose escalation: ORR | Baseline to 2 years | ORR as assessed using the RECIST version 1.1. |
| Phase 1b Dose Expansion: Number of participants with treatment-emergent adverse events (AEs) | Baseline to 2 years | 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 | Baseline to 2 years | 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 | Baseline to 2 years | Laboratory abnormalities as characterized by type, frequency, severity, and timing. |
| Phase 1b Dose Expansion: Duration of Response (Overall and in CNS) | Baseline to 2 years | Response will be evaluated via radiographical tumor assessments by RECIST v1.1 for solid tumors or RANO for primary brain tumors |
| Phase 1b Dose Expansion: Intracranial response | Baseline to 2 years | Intracranial response by RECIST version 1.1 (for brain metastases) |
| Phase 1b Dose Expansion: Progression Free Survival (PFS) | Baseline to 2 years | Response will be evaluated via radiographical tumor assessments by RECIST v1.1 for solid tumors or RANO for primary brain tumors |
| PK Parameters: Maximum Observed Concentration (Cmax) | Baseline to 2 years | Single dose and multiple dose PK will be calculated as data permits |
| PK Parameters: Maximum Plasma Concentration (Tmax) | Baseline to 2 years | Single dose and multiple dose PK will be calculated as data permits |
| PK Parameters: Area Under Curve (AUC) | Baseline to 2 years | Single dose and multiple dose PK will be calculated as data permits |
| PK Parameters: terminal elimination half-life (t½) | Baseline to 2 years | Singe dose and multiple dose PK will be calculated as data permits |
| PK Parameters: Apparent Oral Clearance (CL/F) | Baseline to 2 years | Singe dose and multiple dose PK will be calculated as data permits |
| PK Parameters: Apparent Volume of Distribution (Vz/F) | Baseline to 2 years | Singe dose and multiple dose PK will be calculated as data permits |
Countries
Australia, Brazil, Canada, China, Israel, Japan, United States
Contacts
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Outcome results
None listed