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| ID | Type | Description | Link |
|---|---|---|---|
| BRAF Class 2 | Other Identifier | Alias Study Number |
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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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Monotherapy dose escalation (Part 1) | Experimental | Participants will receive PF-07799933 |
|
| Combination dose escalation (Part 2) | Experimental | Participants will receive PF-07799933 in combination with binimetinib or cetuximab |
|
| Dose expansion (Part 3) - Tumor and mutation specific Cohort 1 | Experimental | Participants will receive PF-07799933 |
|
| Dose expansion (Part 3) - Tumor and mutation specific Cohort 2 | Experimental | Participants will receive PF-07799933 |
|
| Dose expansion (Part 3) - Tumor and mutation specific Cohort 3 | Experimental | Participants will receive PF-07799933 |
|
| Dose expansion (Part 3) - Tumor and mutation specific Cohort 4 |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PF-07799933 | Drug | Tablet |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of participants with dose limiting toxicities (DLTs) (Part 1 and Part 2) | DLTs will be evaluated during the first cycle (21 days) as both a single agent or in combination with binimetinib or cetuximab | Cycle 1 (21 days) |
| Number of participants with treatment-emergent adverse events (AEs) (Part 1 and Part 2) | AEs as characterized by type, frequency, severity, timing, seriousness, and relationship to study therapy | Baseline to 28 days after last dose of study medication |
| Number of participants with clinically significant change from baseline in laboratory abnormalities (Part 1 and Part 2) | Laboratory abnormalities as characterized by type, frequency, severity, and timing | Baseline to 28 days after last dose of study treatment |
| Number of participants with clinically significant change from baseline in vital sign abnormalities (Part 1 and Part 2) | Vital sign abnormalities as characterized by type, frequency, severity, and timing | Baseline to 28 days after last dose of study treatment |
| Dose interruptions due to AEs (Part 1 and Part 2) | Incidence of dose interruptions due to AEs | Baseline to 2 years |
| Dose dose modifications due to AEs (Part 1 and Part 2) | Incidence of dose modifications due to AEs | Baseline to 2 years |
| Discontinuations due to AEs (Part 1 and Part 2) |
| Measure | Description | Time Frame |
|---|---|---|
| Part 1 and Part 2: ORR | ORR as assessed using the RECIST version 1.1. | Baseline to 2 years |
| Part 1/2/3: Intracranial response | Intracranial response by RECIST version 1.1 (for brain metastases) & Response Assessment in Neuro-Oncology (RANO) - for primary brain tumors). |
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This study is seeking participants who meet the following key eligibility criteria:
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Pfizer CT.gov Call Center | Contact | 1-800-718-1021 | ClinicalTrials.gov_Inquiries@pfizer.com |
| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Highlands Oncology Group | Recruiting | Fayetteville | Arkansas | 72703 | United States | |
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| Label | URL |
|---|---|
| To obtain contact information for a study center near you, click here. | View source |
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Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.
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| Experimental |
Participants will receive PF-07799933 in combination with cetuximab |
|
| Dose expansion (Part 3) - Tumor and mutation specific Cohort 5 | Experimental | Participants will receive PF-07799933 in combination with cetuximab and mFOLFOX6 regimen |
|
| Dose expansion (Part 3) - Tumor and mutation specific Cohort 6 | Experimental | Participants will receive PF-07799933 |
|
| Dose expansion (Part 3) - Tumor and mutation specific Cohort 7 | Experimental | Participants will receive PF-07799933 |
|
|
| binimetinib | Drug | Tablet |
|
|
| cetuximab | Biological | Injection for intravenous use |
|
|
| midazolam | Drug | syrup |
|
| fluorouracil | Drug | Injection for intravenous use |
|
| leucovorin | Drug | Injection for intravenous use |
|
| oxaliplatin | Drug | Injection for intravenous use |
|
Incidence of discontinuations due to AEs |
| Baseline to 2 years |
| Overall response rate (ORR) (Part 3) | Response will be evaluated via radiographical tumor assessments by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) | Baseline to 2 years |
| Number of participants with clinically significant physical exam abnormalities (Part 1 and Part 2) | Physical exam abnormalities as as graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 | Baseline to 28 days after last dose of study treatment |
| Baseline to 2 years |
| Part 1 and Part 2: Duration of response | Duration of response | Baseline to 2 years |
| Part 3: Number of participants with treatment-emergent adverse events (AEs) | AEs as characterized by type, frequency, severity, timing, seriousness, and relationship to study therapy | Baseline to 2 years |
| Part 3: Number of participants with clinically significant change from baseline in laboratory abnormalities | Laboratory abnormalities as characterized by type, frequency, severity, and timing | Baseline to 2 years |
| Part 3: Number of participants with clinically significant change from baseline in vital sign abnormalities | Vital sign abnormalities as characterized by type, frequency, severity, and timing | Baseline to 2 years |
| Part 3: Dose interruptions due to AEs | Incidence of dose interruptions due to AEs | Baseline to 2 years |
| Part 3: Dose dose modifications due to AEs | Incidence of dose modifications due to AEs | Baseline to 2 years |
| Part 3: Discontinuations due to AEs | Incidence of discontinuations due to AEs | Baseline to 2 years |
| Part 3: Time to event endpoints in each combination | Time to event endpoints in each combination | Baseline to 2 years |
| Part 3: Disease Control Rate (DCR) | DCR | Baseline to 2 years |
| Part 1/2/3: PK parameters of PF-07799933, Single dose, maximum observed concentration (Cmax) | PK parameters of PF-07799933, Single dose, Cmax | Baseline to 2 years |
| Part 1/2/3: PK parameters of PF-07799933, Single dose, time to maximum plasma concentration (Tmax) | PK parameters of PF-07799933, Single dose, Tmax | Baseline to 2 years |
| 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) | PK parameters of PF-07799933, Single dose, AUClast | Baseline to 2 years |
| Part 1/2/3: PK parameters of PF-07799933, Single dose, area under plasma concentration-time curve over 24 hours (AUC24) | PK parameters of PF-07799933, Single dose, AUC24 | Baseline to 2 years |
| Part 1/2/3: PK parameters of PF-07799933, Single dose, area under plasma concentration-time curve over 48 hours (AUC48) | PK parameters of PF-07799933, Single dose, AUC48 | Baseline to 2 years |
| Part 1/2/3: PK parameters of PF-07799933, Single dose, terminal elimination half life (t½) | PK parameters of PF-07799933, Single dose, t½ | Baseline to 2 years |
| 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) | PK parameters of PF-07799933, Single dose, AUCinf | Baseline to 2 years |
| Part 1/2/3: PK parameters of PF-07799933, Single dose, apparent oral clearance (CL/F) | PK parameters of PF-07799933, Single dose, CL/F | Baseline to 2 years |
| Part 1/2/3: PK parameters of PF-07799933, Single dose, apparent volume of distribution (Vz/F) | PK parameters of PF-07799933, Single dose, Vz/F | Baseline to 2 years |
| Part 1/2/3: PK parameters of PF-07799933, Multiple dose, maximum observed concentration (Cmax) | PK parameters of PF-07799933, Multiple dose, Cmax | Baseline to 2 years |
| Part 1/2/3: PK parameters of PF-07799933, Multiple dose, trough plasma or serum concentration (Ctrough) | PK parameters of PF-07799933, Multiple dose, Ctrough | Baseline to 2 years |
| Part 1/2/3: PK parameters of PF-07799933, Multiple dose, time to maximum plasma concentration (Tmax) | PK parameters of PF-07799933, Multiple dose, Tmax | Baseline to 2 years |
| Part 1/2/3: PK parameters of PF-07799933, Multiple dose, area under the plasma concentration-time curve over the dosing interval (AUCτ) | PK parameters of PF-07799933, Multiple dose, AUCτ | Baseline to 2 years |
| Part 1/2/3: PK parameters of PF-07799933, Multiple dose, CL/F | PK parameters of PF-07799933, Multiple dose, CL/F | Baseline to 2 years |
| Part 1/2/3: PK parameters of PF-07799933, Multiple dose, average plasma concentration (Cav) | PK parameters of PF-07799933, Multiple dose, Cav | Baseline to 2 years |
| Part 1/2/3: PK parameters of PF-07799933, Multiple dose, peak-to-trough ratio (PTR) | PK parameters of PF-07799933, Multiple dose, PTR | Baseline to 2 years |
| Part 1/2/3: PK parameters of PF-07799933, Multiple dose, accumulation ratio (Rac) | PK parameters of PF-07799933, Multiple dose, Rac (AUCτ /AUCsd,τ) | Baseline to 2 years |
| Part 1/2/3: PK parameters of PF-07799933, Multiple dose, t1/2 | PK parameters of PF-07799933, Multiple dose, t1/2 | Baseline to 2 years |
| Part 1/2/3: PK parameters of PF-07799933, Multiple dose, Vz/F | PK parameters of PF-07799933, Multiple dose, Vz/F | Baseline to 2 years |
| Part 3: PK parameters of cytochrome P450 (CYP)3A4 probe substrate midazolam, Cmax | PK parameters of CYP3A4 probe substrate midazolam, Cmax | Baseline to 2 years |
| Part 3: PK parameters of CYP3A4 probe substrate midazolam, Tmax | PK parameters of CYP3A4 probe substrate midazolam, Tmax | Baseline to 2 years |
| Part 3: PK parameters of CYP3A4 probe substrate midazolam, AUClast | PK parameters of CYP3A4 probe substrate midazolam, AUClast | Baseline to 2 years |
| Part 3: PK parameters of CYP3A4 probe substrate midazolam, t½ | PK parameters of CYP3A4 probe substrate midazolam, t½ | Baseline to 2 years |
| Part 3: PK parameters of CYP3A4 probe substrate midazolam, AUCinf | PK parameters of CYP3A4 probe substrate midazolam, AUCinf | Baseline to 2 years |
| Part 3: PK parameters of CYP3A4 probe substrate midazolam, CL/F | PK parameters of CYP3A4 probe substrate midazolam, CL/F | Baseline to 2 years |
| Part 3: PK parameters of CYP3A4 probe substrate midazolam, Vz/F | PK parameters of CYP3A4 probe substrate midazolam, Vz/F | Baseline to 2 years |
| Part 3: TTR | Time to response (TTR) | Baseline to 2 years |
| Part 3: DOR | Duration of response (DOR) | Baseline to 2 years |
| Part 3: PFS | Progression-free survival (PFS) | Baseline to 2 years |
| Part 3: OS | Overall survival (OS) | Baseline to 2 years |
| Number of participants with clinically significant physical exam abnormalities (Part 3) | Physical exam abnormalities as as graded by NCI CTCAE version 5.0 | Baseline to 28 days after last dose of study medication |
| Highlands Oncology Group |
| Recruiting |
| Rogers |
| Arkansas |
| 72758 |
| United States |
| Highlands Oncology Group | Recruiting | Springdale | Arkansas | 72762 | United States |
| Clinical and Translational Research Center (CTRC) | Recruiting | Aurora | Colorado | 80045 | United States |
| UCHealth Sue Anschutz-Rodgers Eye Center | Recruiting | Aurora | Colorado | 80045 | United States |
| University of Colorado Hospital - Anschutz Cancer Pavilion (ACP) | Recruiting | Aurora | Colorado | 80045 | United States |
| University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP) | Recruiting | Aurora | Colorado | 80045 | United States |
| University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP) | Recruiting | Aurora | Colorado | 80045 | United States |
| Sylvester Comprehensive Cancer Center | Recruiting | Miami | Florida | 33136 | United States |
| University of Miami Hospital and Clinics | Recruiting | Miami | Florida | 33136 | United States |
| Brigham and Women's Hospital | Recruiting | Boston | Massachusetts | 02115 | United States |
| Dana-Farber Cancer Institute | Recruiting | Boston | Massachusetts | 02215 | United States |
| Dana-Farber Cancer Institute - Chestnut Hill | Recruiting | Newton | Massachusetts | 02467 | United States |
| Brigitte Harris Cancer Pavilion | Recruiting | Detroit | Michigan | 48202 | United States |
| Henry Ford Hospital | Recruiting | Detroit | Michigan | 48202 | United States |
| Henry Ford Medical Center - Columbus | Recruiting | Novi | Michigan | 48377 | United States |
| CT Scan and Echo Only: Henry Ford Medical Center-Plymouth | Recruiting | Plymouth | Michigan | 48170 | United States |
| MSK Monmouth | Recruiting | Middletown | New Jersey | 07748 | United States |
| MSK David H. Koch Center for Cancer Care | Recruiting | New York | New York | 10021 | United States |
| Memorial Sloan Kettering Cancer Center 53rd street | Recruiting | New York | New York | 10022 | United States |
| Memorial Sloan Kettering Cancer Center | Recruiting | New York | New York | 10065 | United States |
| Cleveland Clinic Taussig Cancer Center Investigational Pharmacy | Recruiting | Cleveland | Ohio | 44106 | United States |
| Cleveland Clinic | Recruiting | Cleveland | Ohio | 44195 | United States |
| Providence Cancer Institute Franz Clinic | Recruiting | Portland | Oregon | 97213 | United States |
| Providence Portland Medical Center | Recruiting | Portland | Oregon | 97213 | United States |
| Sarah Cannon Research Institute - Pharmacy | Recruiting | Nashville | Tennessee | 37203 | United States |
| SCRI Oncology Partners | Recruiting | Nashville | Tennessee | 37203 | United States |
| TriStar Bone Marrow Transplant | Recruiting | Nashville | Tennessee | 37203 | United States |
| TriStar Centennial Medical Center - Cell Processing Lab | Recruiting | Nashville | Tennessee | 37203 | United States |
| TriStar Centennial Medical center | Recruiting | Nashville | Tennessee | 37203 | United States |
| START San Antonio | Recruiting | San Antonio | Texas | 78229 | United States |
| The Ottawa Hospital - General Campus | Recruiting | Ottawa | Ontario | K1H 8L6 | Canada |
| Princess Margaret Cancer Centre | Recruiting | Toronto | Ontario | M5G 1X6 | Canada |
| University Health Network | Recruiting | Toronto | Ontario | M5G 2C4 | Canada |
| Jewish General Hospital | Recruiting | Montreal | Quebec | H3T 1E2 | Canada |
| McGill University Health Centre | Recruiting | Montreal | Quebec | H4A 3J1 | Canada |
| Sourasky Medical Center | Recruiting | Tel Aviv | Central District | 6423906 | Israel |
| Hadassah Medical Center | Recruiting | Jerusalem | 9112001 | Israel |
| Sheba Medical Center | Recruiting | Ramat Gan | 5262000 | Israel |
| Rambam Health Care Campus | Recruiting | Haifa | Ḥeifā | 3109601 | Israel |
| ID | Term |
|---|---|
| D008545 | Melanoma |
| D002289 | Carcinoma, Non-Small-Cell Lung |
| D013964 | Thyroid Neoplasms |
| D005910 | Glioma |
| ID | Term |
|---|---|
| D018358 | Neuroendocrine Tumors |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009380 | Neoplasms, Nerve Tissue |
| D018326 | Nevi and Melanomas |
| D012878 | Skin Neoplasms |
| D009371 | Neoplasms by Site |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D004701 | Endocrine Gland Neoplasms |
| D006258 | Head and Neck Neoplasms |
| D004700 | Endocrine System Diseases |
| D013959 | Thyroid Diseases |
| D018302 | Neoplasms, Neuroepithelial |
| D009375 | Neoplasms, Glandular and Epithelial |
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| ID | Term |
|---|---|
| C581313 | binimetinib |
| D000068818 | Cetuximab |
| D008874 | Midazolam |
| D005472 | Fluorouracil |
| D002955 | Leucovorin |
| D000077150 | Oxaliplatin |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D005575 | Formyltetrahydrofolates |
| D013763 | Tetrahydrofolates |
| D005492 | Folic Acid |
| D011622 | Pterins |
| D011621 | Pteridines |
| D003067 | Coenzymes |
| D045762 | Enzymes and Coenzymes |
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
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