A Study to Learn About the Study Medicine Called PF-07799933 in People With Advanced Solid Tumors With BRAF Alterations.
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: PF-07799933, binimetinib, cetuximab, midazolam.
- Who it may be relevant to
- Registry conditions: Melanoma, Non-Small-Cell Lung Cancer, Thyroid Cancer, Glioma. Basic parameters: from 16 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States, Canada, Israel
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
A PHASE 1, OPEN-LABEL, DOSE ESCALATION AND DOSE EXPANSION STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND ANTI TUMOR ACTIVITY OF PF-07799933 (ARRY-440) AS A SINGLE AGENT AND IN COMBINATION THERAPY IN PARTICIPANTS 16 YEARS AND OLDER WITH ADVANCED SOLID TUMORS WITH BRAF ALTERATIONS
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 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
- Drug PF-07799933
Tablet - Drug binimetinib
Tablet - Biological cetuximab
Injection for intravenous use - Drug midazolam
syrup - Drug fluorouracil
Injection for intravenous use - Drug leucovorin
Injection for intravenous use - Drug oxaliplatin
Injection for intravenous use
Primary outcome measures
- Number of participants with dose limiting toxicities (DLTs) (Part 1 and Part 2) [Time frame: Cycle 1 (21 days)]
- Number of participants with treatment-emergent adverse events (AEs) (Part 1 and Part 2) [Time frame: 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) [Time frame: 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) [Time frame: Baseline to 28 days after last dose of study treatment]
- Dose interruptions due to AEs (Part 1 and Part 2) [Time frame: Baseline to 2 years]
- Dose dose modifications due to AEs (Part 1 and Part 2) [Time frame: Baseline to 2 years]
- Discontinuations due to AEs (Part 1 and Part 2) [Time frame: Baseline to 2 years]
- Overall response rate (ORR) (Part 3) [Time frame: Baseline to 2 years]
- Number of participants with clinically significant physical exam abnormalities (Part 1 and Part 2) [Time frame: Baseline to 28 days after last dose of study treatment]
Secondary outcome measures (12)
- Part 1 and Part 2: ORR [Time frame: Baseline to 2 years]
- Part 1/2/3: Intracranial response [Time frame: Baseline to 2 years]
- Part 1 and Part 2: Duration of response [Time frame: Baseline to 2 years]
- Part 3: Number of participants with treatment-emergent adverse events (AEs) [Time frame: Baseline to 2 years]
- Part 3: Number of participants with clinically significant change from baseline in laboratory abnormalities [Time frame: Baseline to 2 years]
- Part 3: Number of participants with clinically significant change from baseline in vital sign abnormalities [Time frame: Baseline to 2 years]
- Part 3: Dose interruptions due to AEs [Time frame: Baseline to 2 years]
- Part 3: Dose dose modifications due to AEs [Time frame: Baseline to 2 years]
- Part 3: Discontinuations due to AEs [Time frame: Baseline to 2 years]
- Part 3: Time to event endpoints in each combination [Time frame: Baseline to 2 years]
- Part 3: Disease Control Rate (DCR) [Time frame: Baseline to 2 years]
- Part 1/2/3: PK parameters of PF-07799933, Single dose, maximum observed concentration (Cmax) [Time frame: Baseline to 2 years]
Eligibility 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).
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Non-randomized
- Model
- Sequential
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
United States · 31 centers
- Highlands Oncology Group, PA — Fayetteville
- Highlands Oncology Group, PA — Rogers
- Highlands Oncology Group, PA — Springdale
- Clinical and Translational Research Center (CTRC) — Aurora
- UCHealth Sue Anschutz-Rodgers Eye Center — Aurora
- University of Colorado Hospital - Anschutz Cancer Pavilion (ACP) — Aurora
- University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP) — Aurora
- University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP) — Aurora
- … and 23 more centers
Canada · 5 centers
- The Ottawa Hospital - General Campus — Ottawa
- Princess Margaret Cancer Centre — Toronto
- University Health Network — Toronto
- Jewish General Hospital — Montreal
- McGill University Health Centre — Montreal
Israel · 4 centers
- Sourasky Medical Center — Tel Aviv
- Hadassah Medical Center — Jerusalem
- Sheba Medical Center — Ramat Gan
- Rambam Health Care Campus — Haifa
Identifiers
NCT: NCT05355701 · C4761001 · BRAF Class 2