Advanced Colorectal Cancer (Part 1), Glioma, Melanoma, Non-Small-Cell Lung Cancer, Thyroid Cancer
Conditions
Brief 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.
Interventions
DRUGPF-07799933
Tablet
DRUGbinimetinib
Tablet
BIOLOGICALcetuximab
Injection for intravenous use
DRUGmidazolam
syrup
DRUGfluorouracil
Injection for intravenous use
DRUGleucovorin
Injection for intravenous use
DRUGoxaliplatin
Injection for intravenous use
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
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with clinically significant change from baseline in laboratory abnormalities (Part 1 and Part 2) | Baseline to 28 days after last dose of study treatment | Laboratory abnormalities as characterized by type, frequency, severity, and timing |
| Number of participants with clinically significant change from baseline in vital sign abnormalities (Part 1 and Part 2) | Baseline to 28 days after last dose of study treatment | Vital sign abnormalities as characterized by type, frequency, severity, and timing |
| Dose interruptions due to AEs (Part 1 and Part 2) | Baseline to 2 years | Incidence of dose interruptions due to AEs |
| Dose dose modifications due to AEs (Part 1 and Part 2) | Baseline to 2 years | Incidence of dose modifications due to AEs |
| Discontinuations due to AEs (Part 1 and Part 2) | Baseline to 2 years | Incidence of discontinuations due to AEs |
| Overall response rate (ORR) (Part 3) | Baseline to 2 years | Response will be evaluated via radiographical tumor assessments by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) |
| Number of participants with clinically significant physical exam abnormalities (Part 1 and Part 2) | 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 |
| Number of participants with dose limiting toxicities (DLTs) (Part 1 and Part 2) | Cycle 1 (21 days) | DLTs will be evaluated during the first cycle (21 days) as both a single agent or in combination with binimetinib or cetuximab |
| Number of participants with treatment-emergent adverse events (AEs) (Part 1 and Part 2) | Baseline to 28 days after last dose of study medication | AEs as characterized by type, frequency, severity, timing, seriousness, and relationship to study therapy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1/2/3: PK parameters of PF-07799933, Multiple dose, peak-to-trough ratio (PTR) | Baseline to 2 years | PK parameters of PF-07799933, Multiple dose, PTR |
| Part 1/2/3: PK parameters of PF-07799933, Multiple dose, accumulation ratio (Rac) | Baseline to 2 years | PK parameters of PF-07799933, Multiple dose, Rac (AUCτ /AUCsd,τ) |
| Part 1/2/3: PK parameters of PF-07799933, Multiple dose, t1/2 | Baseline to 2 years | PK parameters of PF-07799933, Multiple dose, t1/2 |
| Part 1/2/3: PK parameters of PF-07799933, Multiple dose, Vz/F | Baseline to 2 years | PK parameters of PF-07799933, Multiple dose, Vz/F |
| Part 3: PK parameters of cytochrome P450 (CYP)3A4 probe substrate midazolam, Cmax | Baseline to 2 years | PK parameters of CYP3A4 probe substrate midazolam, Cmax |
| Part 3: PK parameters of CYP3A4 probe substrate midazolam, Tmax | Baseline to 2 years | PK parameters of CYP3A4 probe substrate midazolam, Tmax |
| Part 3: PK parameters of CYP3A4 probe substrate midazolam, AUClast | Baseline to 2 years | PK parameters of CYP3A4 probe substrate midazolam, AUClast |
| Part 3: PK parameters of CYP3A4 probe substrate midazolam, t½ | Baseline to 2 years | PK parameters of CYP3A4 probe substrate midazolam, t½ |
| Part 3: PK parameters of CYP3A4 probe substrate midazolam, AUCinf | Baseline to 2 years | PK parameters of CYP3A4 probe substrate midazolam, AUCinf |
| Part 3: PK parameters of CYP3A4 probe substrate midazolam, CL/F | Baseline to 2 years | PK parameters of CYP3A4 probe substrate midazolam, CL/F |
| Part 3: PK parameters of CYP3A4 probe substrate midazolam, Vz/F | Baseline to 2 years | PK parameters of CYP3A4 probe substrate midazolam, Vz/F |
| Part 3: TTR | Baseline to 2 years | Time to response (TTR) |
| Part 3: DOR | Baseline to 2 years | Duration of response (DOR) |
| Part 3: PFS | Baseline to 2 years | Progression-free survival (PFS) |
| Part 3: OS | Baseline to 2 years | Overall survival (OS) |
| Number of participants with clinically significant physical exam abnormalities (Part 3) | Baseline to 28 days after last dose of study medication | Physical exam abnormalities as as graded by NCI CTCAE version 5.0 |
| Part 1/2/3: PK parameters of PF-07799933, Single dose, area under plasma concentration-time curve over 48 hours (AUC48) | Baseline to 2 years | PK parameters of PF-07799933, Single dose, AUC48 |
| Part 1/2/3: PK parameters of PF-07799933, Single dose, terminal elimination half life (t½) | Baseline to 2 years | PK parameters of PF-07799933, Single dose, t½ |
| Part 1/2/3: PK parameters of PF-07799933, Single dose, maximum observed concentration (Cmax) | Baseline to 2 years | PK parameters of PF-07799933, Single dose, Cmax |
| Part 1/2/3: PK parameters of PF-07799933, Single dose, time to maximum plasma concentration (Tmax) | Baseline to 2 years | PK parameters of PF-07799933, Single dose, Tmax |
| Part 1/2/3: PK parameters of PF-07799933, Single dose, area under the plasma concentration-time curve from time 0 to the last time point of quantifiable concentration (AUClast) | Baseline to 2 years | PK parameters of PF-07799933, Single dose, AUClast |
| Part 1/2/3: PK parameters of PF-07799933, Single dose, area under plasma concentration-time curve over 24 hours (AUC24) | Baseline to 2 years | PK parameters of PF-07799933, Single dose, AUC24 |
| Part 1 and Part 2: ORR | Baseline to 2 years | ORR as assessed using the RECIST version 1.1. |
| Part 1/2/3: Intracranial response | Baseline to 2 years | Intracranial response by RECIST version 1.1 (for brain metastases) \& Response Assessment in Neuro-Oncology (RANO) - for primary brain tumors). |
| Part 1 and Part 2: Duration of response | Baseline to 2 years | Duration of response |
| Part 3: 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 |
| Part 3: 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 |
| Part 3: 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 |
| Part 3: Dose interruptions due to AEs | Baseline to 2 years | Incidence of dose interruptions due to AEs |
| Part 3: Dose dose modifications due to AEs | Baseline to 2 years | Incidence of dose modifications due to AEs |
| Part 3: Discontinuations due to AEs | Baseline to 2 years | Incidence of discontinuations due to AEs |
| Part 3: Time to event endpoints in each combination | Baseline to 2 years | Time to event endpoints in each combination |
| Part 1/2/3: PK parameters of PF-07799933, Single dose, area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUCinf) | Baseline to 2 years | PK parameters of PF-07799933, Single dose, AUCinf |
| Part 3: Disease Control Rate (DCR) | Baseline to 2 years | DCR |
| Part 1/2/3: PK parameters of PF-07799933, Single dose, apparent oral clearance (CL/F) | Baseline to 2 years | PK parameters of PF-07799933, Single dose, CL/F |
| Part 1/2/3: PK parameters of PF-07799933, Single dose, apparent volume of distribution (Vz/F) | Baseline to 2 years | PK parameters of PF-07799933, Single dose, Vz/F |
| Part 1/2/3: PK parameters of PF-07799933, Multiple dose, maximum observed concentration (Cmax) | Baseline to 2 years | PK parameters of PF-07799933, Multiple dose, Cmax |
| Part 1/2/3: PK parameters of PF-07799933, Multiple dose, trough plasma or serum concentration (Ctrough) | Baseline to 2 years | PK parameters of PF-07799933, Multiple dose, Ctrough |
| Part 1/2/3: PK parameters of PF-07799933, Multiple dose, time to maximum plasma concentration (Tmax) | Baseline to 2 years | PK parameters of PF-07799933, Multiple dose, Tmax |
| Part 1/2/3: PK parameters of PF-07799933, Multiple dose, area under the plasma concentration-time curve over the dosing interval (AUCτ) | Baseline to 2 years | PK parameters of PF-07799933, Multiple dose, AUCτ |
| Part 1/2/3: PK parameters of PF-07799933, Multiple dose, CL/F | Baseline to 2 years | PK parameters of PF-07799933, Multiple dose, CL/F |
| Part 1/2/3: PK parameters of PF-07799933, Multiple dose, average plasma concentration (Cav) | Baseline to 2 years | PK parameters of PF-07799933, Multiple dose, Cav |
Countries
Canada, Israel, United States
Contacts
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Outcome results
None listed