A Study to Learn About the Study Medicine Called PF-07799933 in People With Advanced Solid Tumors With BRAF Alterations.

Melanoma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05355701
• Other study ID #: C4761001
• Secondary ID: BRAF Class 2
• Status: Recruiting
• Phase: Phase 1
• Start date: July 5, 2022
• Est. completion date: February 13, 2029

Study information

• Verified date: June 2024
• Source: Pfizer
• Contact: Pfizer CT.gov Call Center
• Phone: 1-800-718-1021
• Email: ClinicalTrials.gov_Inquiries[@]pfizer.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 156
• Est. completion date: February 13, 2029
• Est. primary completion date: August 13, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Glioma
• Melanoma
• Non-Small-Cell Lung Cancer
• Thyroid Cancer
• Thyroid Neoplasms

Intervention

Drug:
• PF-07799933
Tablet
• binimetinib
Tablet

Biological:
• cetuximab
Injection for intravenous use

Locations

Country	Name	City	State
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Jewish General Hospital	Montreal	Quebec
Canada	McGill University Health Centre	Montréal	Quebec
Canada	The Ottawa Hospital - General Campus	Ottawa	Ontario
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Israel	Rambam Health Care Campus	Haifa	?eifa
Israel	Hadassah Medical Center	Jerusalem	Yerushalayim
Israel	Rabin Medical Center	Petah Tikva	Hamerkaz
Israel	Sheba Medical Center	Ramat Gan	Hamerkaz
Israel	Sourasky Medical Center	Tel Aviv	Tell Abib
Israel	Sourasky Medical Center	Tel Aviv, Yaffo	Hamerkaz
United States	Clinical And Translational Research Center	Aurora	Colorado
United States	Clinical and Translational Research Center (CTRC)	Aurora	Colorado
United States	UCHealth Sue Anschutz-Rodgers Eye Center	Aurora	Colorado
United States	University of Colorado Anschutz Medical Campus	Aurora	Colorado
United States	University of Colorado Hospital - Anschutz Cancer Pavilion (ACP)	Aurora	Colorado
United States	University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP)	Aurora	Colorado
United States	University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP)	Aurora	Colorado
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Cleveland Clinic	Cleveland	Ohio
United States	Cleveland Clinic Taussig Cancer Center Investigational Pharmacy	Cleveland	Ohio
United States	Cleveland Clinic Taussing Cancer Center Investigational Pharmacy	Cleveland	Ohio
United States	Brigitte Harris Cancer Pavilion	Detroit	Michigan
United States	Henry Ford Hospital	Detroit	Michigan
United States	Highlands Oncology Group	Fayetteville	Arkansas
United States	University of Miami Hospital and Clinics, Sylvester Cancer Center	Miami	Florida
United States	University of Miami Hospital and Clinics, Sylvester Cancer Center	Miami	Florida
United States	MSK Monmouth	Middletown	New Jersey
United States	Sarah Cannon Research Institute - Pharmacy	Nashville	Tennessee
United States	Tennessee Oncology PLLC	Nashville	Tennessee
United States	Tennessee Oncology, PLLC	Nashville	Tennessee
United States	TriStar Bone Marrow Transplant	Nashville	Tennessee
United States	TriStar Centennial Medical center	Nashville	Tennessee
United States	TriStar Centennial Medical Center - Cell Processing Lab	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Memorial Sloan Kettering Cancer Center 53rd street	New York	New York
United States	MSK David H. Koch Center for Cancer Care	New York	New York
United States	DFCI Chestnut Hill	Newton	Massachusetts
United States	Henry Ford Medical Center - Columbus	Novi	Michigan
United States	Providence Cancer Institute Franz Clinic	Portland	Oregon
United States	Providence Portland Medical Center	Portland	Oregon
United States	Highlands Oncology Group	Rogers	Arkansas
United States	South Texas Accelerated Research Therapeutics (START)	San Antonio	Texas
United States	Highlands Oncology Group	Springdale	Arkansas

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Canada,  Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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
Primary	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
Primary	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
Primary	Dose interruptions due to AEs (Part 1 and Part 2)	Incidence of dose interruptions due to AEs	Baseline to 2 years
Primary	Dose dose modifications due to AEs (Part 1 and Part 2)	Incidence of dose modifications due to AEs	Baseline to 2 years
Primary	Discontinuations due to AEs (Part 1 and Part 2)	Incidence of discontinuations due to AEs	Baseline to 2 years
Primary	MTD (Part 1 and Part 2)	Maximum tolerated dose (MTD)	Cycle 1 (21 days)
Primary	RDE (Part 1 and Part 2)	Recommended dose for expansion (RDE)	Cycle 1 (21 days)
Primary	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
Primary	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
Secondary	Part 1 and Part 2: ORR	ORR as assessed using the RECIST version 1.1.	Baseline to 2 years
Secondary	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).	Baseline to 2 years
Secondary	Part 1 and Part 2: Duration of response	Duration of response	Baseline to 2 years
Secondary	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
Secondary	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
Secondary	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
Secondary	Part 3: Dose interruptions due to AEs	Incidence of dose interruptions due to AEs	Baseline to 2 years
Secondary	Part 3: Dose dose modifications due to AEs	Incidence of dose modifications due to AEs	Baseline to 2 years
Secondary	Part 3: Discontinuations due to AEs	Incidence of discontinuations due to AEs	Baseline to 2 years
Secondary	Part 3: Time to event endpoints in each combination	Time to event endpoints in each combination	Baseline to 2 years
Secondary	Part 3: Disease Control Rate (DCR)	DCR	Baseline to 2 years
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Part 1/2/3: PK parameters of PF-07799933, Multiple dose, area under the plasma concentration-time curve over the dosing interval (AUCt)	PK parameters of PF-07799933, Multiple dose, AUCt	Baseline to 2 years
Secondary	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
Secondary	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
Secondary	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
Secondary	Part 1/2/3: PK parameters of PF-07799933, Multiple dose, accumulation ratio (Rac)	PK parameters of PF-07799933, Multiple dose, Rac (AUCt /AUCsd,t)	Baseline to 2 years
Secondary	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
Secondary	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
Secondary	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
Secondary	Part 3: PK parameters of CYP3A4 probe substrate midazolam, Tmax	PK parameters of CYP3A4 probe substrate midazolam, Tmax	Baseline to 2 years
Secondary	Part 3: PK parameters of CYP3A4 probe substrate midazolam, AUClast	PK parameters of CYP3A4 probe substrate midazolam, AUClast	Baseline to 2 years
Secondary	Part 3: PK parameters of CYP3A4 probe substrate midazolam, t½	PK parameters of CYP3A4 probe substrate midazolam, t½	Baseline to 2 years
Secondary	Part 3: PK parameters of CYP3A4 probe substrate midazolam, AUCinf	PK parameters of CYP3A4 probe substrate midazolam, AUCinf	Baseline to 2 years
Secondary	Part 3: PK parameters of CYP3A4 probe substrate midazolam, CL/F	PK parameters of CYP3A4 probe substrate midazolam, CL/F	Baseline to 2 years
Secondary	Part 3: PK parameters of CYP3A4 probe substrate midazolam, Vz/F	PK parameters of CYP3A4 probe substrate midazolam, Vz/F	Baseline to 2 years
Secondary	Part 3: TTR	Time to response (TTR)	Baseline to 2 years
Secondary	Part 3: DOR	Duration of response (DOR)	Baseline to 2 years
Secondary	Part 3: PFS	Progression-free survival (PFS)	Baseline to 2 years
Secondary	Part 3: OS	Overall survival (OS)	Baseline to 2 years
Secondary	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

External Links

•   To obtain contact information for a study center near you, click here.