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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Glioma; Melanoma; Thyroid Cancer; Non-Small-Cell Lung Cancer
• Intervention / Treatment: Drug: PF-07799933; Drug: binimetinib; Biological: cetuximab

• Study Type: Interventional
• Enrollment (Estimated): 174
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Pfizer CT.gov Call Center; Phone Number: 1-800-718-1021; Email: ClinicalTrials.gov_Inquiries@pfizer.com

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Not yet recruiting
      • Cross Cancer Institute
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Recruiting
      • The Ottawa Hospital - General Campus
    • Toronto, Ontario, Canada, M5G 2M9
      • Not yet recruiting
      • Princess Margaret Cancer Centre
  • Quebec
    • Montréal, Quebec, Canada, H4A 3J1
      • Recruiting
      • McGill University Health Centre
• Israel
  • Hamerkaz
    • Petah Tikva, Hamerkaz, Israel, 4941492
      • Not yet recruiting
      • Rabin Medical Center
    • Ramat Gan, Hamerkaz, Israel, 5265601
      • Not yet recruiting
      • Sheba Medical Center
    • Tel Aviv, Yaffo, Hamerkaz, Israel, 6423906
      • Not yet recruiting
      • Sourasky Medical Center
  • Tell Abīb
    • Tel Aviv, Tell Abīb, Israel, 6423906
      • Not yet recruiting
      • Sourasky Medical Center
  • Yerushalayim
    • Jerusalem, Yerushalayim, Israel, 9112001
      • Recruiting
      • Hadassah Medical Center
  • Ḥeifā
    • Haifa, Ḥeifā, Israel, 3109601
      • Not yet recruiting
      • Rambam Health Care Campus
• United States
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Recruiting
      • Highlands Oncology Group
    • Rogers, Arkansas, United States, 72758
      • Recruiting
      • Highlands Oncology Group
    • Springdale, Arkansas, United States, 72762
      • Recruiting
      • Highlands Oncology Group
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado Anschutz Medical Campus
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado Hospital - Anschutz Cancer Pavilion (ACP)
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP)
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP)
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • UCHealth Sue Anschutz-Rodgers Eye Center
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • Clinical and Translational Research Center
  • Florida
    • Miami, Florida, United States, 33136
      • Not yet recruiting
      • University of Miami Hospital and Clinics, Sylvester Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana-Farber Cancer Institute
    • Newton, Massachusetts, United States, 02459
      • Recruiting
      • DFCI Chestnut Hill
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Recruiting
      • Henry Ford Hospital
    • Detroit, Michigan, United States, 48202
      • Recruiting
      • Brigitte Harris Cancer Pavilion
    • Novi, Michigan, United States, 48377
      • Recruiting
      • Henry Ford Medical Center - Columbus
  • New Jersey
    • Middletown, New Jersey, United States, 07748
      • Recruiting
      • MSK Monmouth
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10021
      • Recruiting
      • MSK David H. Koch Center for Cancer Care
    • New York, New York, United States, 10022
      • Recruiting
      • Memorial Sloan Kettering Cancer Center 53rd street
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Not yet recruiting
      • Cleveland Clinic
    • Cleveland, Ohio, United States, 44106
      • Not yet recruiting
      • Cleveland Clinic Taussig Cancer Center Investigational Pharmacy
    • Cleveland, Ohio, United States, 44106
      • Not yet recruiting
      • Cleveland Clinic Taussing Cancer Center Investigational Pharmacy
  • Oregon
    • Portland, Oregon, United States, 97213
      • Recruiting
      • Providence Portland Medical Center
    • Portland, Oregon, United States, 97213
      • Recruiting
      • Providence Cancer Institute Franz Clinic
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Tennessee Oncology, PLLC
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Tennessee Oncology PLLC
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • TriStar Centennial Medical center
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Sarah Cannon Research Institute - Pharmacy
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • TriStar Bone Marrow Transplant
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • TriStar Centennial Medical Center - Cell Processing Lab
  • Texas
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • South Texas Accelerated Research Therapeutics (START)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Monotherapy dose escalation (Part 1); Participants will receive PF-07799933	Drug: PF-07799933; Tablet; Other Names: ARRY-440
Experimental: Combination dose escalation (Part 2); Participants will receive PF-07799933 in combination with binimetinib or cetuximab	Drug: PF-07799933; Tablet; Other Names: ARRY-440; Drug: binimetinib; Tablet; Other Names: Mektovi, PF-06811462, MEK162; Biological: cetuximab; Injection for intravenous use; Other Names: Erbitux
Experimental: Dose expansion (Part 3) - Tumor and mutation specific Cohort 1; Participants will receive PF-07799933	Drug: PF-07799933; Tablet; Other Names: ARRY-440
Experimental: Dose expansion (Part 3) - Tumor and mutation specific Cohort 2; Participants will receive PF-07799933	Drug: PF-07799933; Tablet; Other Names: ARRY-440; Drug: binimetinib; Tablet; Other Names: Mektovi, PF-06811462, MEK162

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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)	Incidence of discontinuations due to AEs	Baseline to 2 years
MTD (Part 1 and Part 2)	Maximum tolerated dose (MTD)	Cycle 1 (21 days)
RDE (Part 1 and Part 2)	Recommended dose for expansion (RDE)	Cycle 1 (21 days)
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

Secondary Outcome Measures

Outcome Measure	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).	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

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2022
• Primary Completion (Estimated): June 28, 2027
• Study Completion (Estimated): December 29, 2028

Study Registration Dates

• First Submitted: April 26, 2022
• First Submitted That Met QC Criteria: April 26, 2022
• First Posted (Actual): May 2, 2022

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Endocrine System Diseases; Endocrine Gland Neoplasms; Thyroid Diseases; Head and Neck Neoplasms; Thyroid Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Cetuximab
• Other Study ID Numbers: C4761001 (Alias Study Number); BRAF Class 2 (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes