Clinical trial NCT05355701: A Study to Learn About the Study Medicine Called PF-07799933 in People With Advanced Solid Tumors With BRAF Alterations.
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Melanoma
Non-Small-Cell Lung Cancer
Thyroid Cancer
Glioma
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2022-05-02
Enrollment: 156
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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 (called binimetinib) 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. 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.


Eligibility criteria: This study is seeking participants who meet the following 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 and Part 2).
* Tumor specific cohorts (melanoma, colorectal cancer) must have received specific prior approved therapies

Exclusion Criteria:

* Brain metastasis larger than 4 cm
* Systemic anti-cancer therapy or small molecule therapeutics ongoing at the start of study treatment.
* For participants who may get binimetinib on study, history or current evidence of retinal vein occlusion (RVO) or concurrent neuromuscular disorder associated with elevated creatine kinase (CK)

Primary outcomes:
measure: Number of participants with dose limiting toxicities (DLTs) (Part 1 and Part 2)
timeFrame: Cycle 1 (21 days)
measure: Number of participants with treatment-emergent adverse events (AEs) (Part 1 and Part 2)
timeFrame: Baseline to 28 days after last dose of study medication
measure: Number of participants with clinically significant change from baseline in laboratory abnormalities (Part 1 and Part 2)
timeFrame: Baseline to 28 days after last dose of study treatment
measure: Number of participants with clinically significant change from baseline in vital sign abnormalities (Part 1 and Part 2)
timeFrame: Baseline to 28 days after last dose of study treatment
measure: Dose interruptions due to AEs (Part 1 and Part 2)
timeFrame: Baseline to 2 years
measure: Dose dose modifications due to AEs (Part 1 and Part 2)
timeFrame: Baseline to 2 years
measure: Discontinuations due to AEs (Part 1 and Part 2)
timeFrame: Baseline to 2 years
measure: MTD (Part 1 and Part 2)
timeFrame: Cycle 1 (21 days)
measure: RDE (Part 1 and Part 2)
timeFrame: Cycle 1 (21 days)
measure: Overall response rate (ORR) (Part 3)
timeFrame: Baseline to 2 years
measure: Number of participants with clinically significant physical exam abnormalities (Part 1 and Part 2)
timeFrame: Baseline to 28 days after last dose of study treatment
Secondary outcomes:
measure: Part 1 and Part 2: ORR
timeFrame: Baseline to 2 years
measure: Part 1/2/3: Intracranial response
timeFrame: Baseline to 2 years
measure: Part 1 and Part 2: Duration of response
timeFrame: Baseline to 2 years
measure: Part 3: Number of participants with treatment-emergent adverse events (AEs)
timeFrame: Baseline to 2 years
measure: Part 3: Number of participants with clinically significant change from baseline in laboratory abnormalities
timeFrame: Baseline to 2 years
measure: Part 3: Number of participants with clinically significant change from baseline in vital sign abnormalities
timeFrame: Baseline to 2 years
measure: Part 3: Dose interruptions due to AEs
timeFrame: Baseline to 2 years
measure: Part 3: Dose dose modifications due to AEs
timeFrame: Baseline to 2 years
measure: Part 3: Discontinuations due to AEs
timeFrame: Baseline to 2 years
measure: Part 3: Time to event endpoints in each combination
timeFrame: Baseline to 2 years
measure: Part 3: Disease Control Rate (DCR)
timeFrame: Baseline to 2 years
measure: Part 1/2/3: PK parameters of PF-07799933, Single dose, maximum observed concentration (Cmax)
timeFrame: Baseline to 2 years
measure: Part 1/2/3: PK parameters of PF-07799933, Single dose, time to maximum plasma concentration (Tmax)
timeFrame: Baseline to 2 years
measure: 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)
timeFrame: Baseline to 2 years
measure: Part 1/2/3: PK parameters of PF-07799933, Single dose, area under plasma concentration-time curve over 24 hours (AUC24)
timeFrame: Baseline to 2 years
measure: Part 1/2/3: PK parameters of PF-07799933, Single dose, area under plasma concentration-time curve over 48 hours (AUC48)
timeFrame: Baseline to 2 years
measure: Part 1/2/3: PK parameters of PF-07799933, Single dose, terminal elimination half life (t½)
timeFrame: Baseline to 2 years
measure: 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)
timeFrame: Baseline to 2 years
measure: Part 1/2/3: PK parameters of PF-07799933, Single dose, apparent oral clearance (CL/F)
timeFrame: Baseline to 2 years
measure: Part 1/2/3: PK parameters of PF-07799933, Single dose, apparent volume of distribution (Vz/F)
timeFrame: Baseline to 2 years
measure: Part 1/2/3: PK parameters of PF-07799933, Multiple dose, maximum observed concentration (Cmax)
timeFrame: Baseline to 2 years
measure: Part 1/2/3: PK parameters of PF-07799933, Multiple dose, trough plasma or serum concentration (Ctrough)
timeFrame: Baseline to 2 years
measure: Part 1/2/3: PK parameters of PF-07799933, Multiple dose, time to maximum plasma concentration (Tmax)
timeFrame: Baseline to 2 years
measure: Part 1/2/3: PK parameters of PF-07799933, Multiple dose, area under the plasma concentration-time curve over the dosing interval (AUCτ)
timeFrame: Baseline to 2 years
measure: Part 1/2/3: PK parameters of PF-07799933, Multiple dose, CL/F
timeFrame: Baseline to 2 years
measure: Part 1/2/3: PK parameters of PF-07799933, Multiple dose, average plasma concentration (Cav)
timeFrame: Baseline to 2 years
measure: Part 1/2/3: PK parameters of PF-07799933, Multiple dose, peak-to-trough ratio (PTR)
timeFrame: Baseline to 2 years
measure: Part 1/2/3: PK parameters of PF-07799933, Multiple dose, accumulation ratio (Rac)
timeFrame: Baseline to 2 years
measure: Part 1/2/3: PK parameters of PF-07799933, Multiple dose, t1/2
timeFrame: Baseline to 2 years
measure: Part 1/2/3: PK parameters of PF-07799933, Multiple dose, Vz/F
timeFrame: Baseline to 2 years
measure: Part 3: PK parameters of cytochrome P450 (CYP)3A4 probe substrate midazolam, Cmax
timeFrame: Baseline to 2 years
measure: Part 3: PK parameters of CYP3A4 probe substrate midazolam, Tmax
timeFrame: Baseline to 2 years
measure: Part 3: PK parameters of CYP3A4 probe substrate midazolam, AUClast
timeFrame: Baseline to 2 years
measure: Part 3: PK parameters of CYP3A4 probe substrate midazolam, t½
timeFrame: Baseline to 2 years
measure: Part 3: PK parameters of CYP3A4 probe substrate midazolam, AUCinf
timeFrame: Baseline to 2 years
measure: Part 3: PK parameters of CYP3A4 probe substrate midazolam, CL/F
timeFrame: Baseline to 2 years
measure: Part 3: PK parameters of CYP3A4 probe substrate midazolam, Vz/F
timeFrame: Baseline to 2 years
measure: Part 3: TTR
timeFrame: Baseline to 2 years
measure: Part 3: DOR
timeFrame: Baseline to 2 years
measure: Part 3: PFS
timeFrame: Baseline to 2 years
measure: Part 3: OS
timeFrame: Baseline to 2 years
measure: Number of participants with clinically significant physical exam abnormalities (Part 3)
timeFrame: Baseline to 28 days after last dose of study medication
Other outcomes:
Locations:
city: Fayetteville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Rogers
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Springdale
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Aurora
country: United States
facility: Clinical and Translational Research Center (CTRC)
state: Colorado
city: Aurora
country: United States
facility: UCHealth Sue Anschutz-Rodgers Eye Center
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Hospital - Anschutz Cancer Pavilion (ACP)
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP)
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP)
state: Colorado
city: Miami
country: United States
facility: University of Miami Hospital and Clinics, Sylvester Cancer Center
state: Florida
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Newton
country: United States
facility: DFCI Chestnut Hill
state: Massachusetts
city: Detroit
country: United States
facility: Brigitte Harris Cancer Pavilion
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Novi
country: United States
facility: Henry Ford Medical Center - Columbus
state: Michigan
city: Middletown
country: United States
facility: MSK Monmouth
state: New Jersey
city: New York
country: United States
facility: MSK David H. Koch Center for Cancer Care
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center 53rd street
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center Investigational Pharmacy
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Portland
country: United States
facility: Providence Cancer Institute Franz Clinic
state: Oregon
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Nashville
country: United States
facility: Sarah Cannon Research Institute - Pharmacy
state: Tennessee
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Nashville
country: United States
facility: TriStar Bone Marrow Transplant
state: Tennessee
city: Nashville
country: United States
facility: TriStar Centennial Medical Center - Cell Processing Lab
state: Tennessee
city: Nashville
country: United States
facility: TriStar Centennial Medical center
state: Tennessee
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics (START)
state: Texas
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Ottawa
country: Canada
facility: The Ottawa Hospital - General Campus
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Montréal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
state: Hamerkaz
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center
state: Hamerkaz
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
state: Yerushalayim
city: Haifa
country: Israel
facility: Rambam Health Care Campus
state: Ḥeifā
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: