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

• ClinicalTrials.gov Identifier: NCT05355701
• Recruitment Status: Recruiting
• First Posted: May 2, 2022
• Last Update Posted: April 30, 2024
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: April 26, 2022
• First Posted Date: May 2, 2022
• Last Update Posted Date: April 30, 2024
• Actual Study Start Date: July 5, 2022
• Estimated Primary Completion Date: July 29, 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 26, 2022)

• Number of participants with dose limiting toxicities (DLTs) (Part 1 and Part 2) [ Time Frame: Cycle 1 (21 days) ]
  DLTs will be evaluated during the first cycle (21 days) as both a single agent or in combination with binimetinib or cetuximab
• 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 ]
  AEs as characterized by type, frequency, severity, timing, seriousness, and relationship to study therapy
• 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 ]
  Laboratory abnormalities as characterized by type, frequency, severity, and timing
• 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 ]
  Vital sign abnormalities as characterized by type, frequency, severity, and timing
• Dose interruptions due to AEs (Part 1 and Part 2) [ Time Frame: Baseline to 2 years ]
  Incidence of dose interruptions due to AEs
• Dose dose modifications due to AEs (Part 1 and Part 2) [ Time Frame: Baseline to 2 years ]
  Incidence of dose modifications due to AEs
• Discontinuations due to AEs (Part 1 and Part 2) [ Time Frame: Baseline to 2 years ]
  Incidence of discontinuations due to AEs
• MTD (Part 1 and Part 2) [ Time Frame: Cycle 1 (21 days) ]
  Maximum tolerated dose (MTD)
• RDE (Part 1 and Part 2) [ Time Frame: Cycle 1 (21 days) ]
  Recommended dose for expansion (RDE)
• Overall response rate (ORR) (Part 3) [ Time Frame: Baseline to 2 years ]
  Response will be evaluated via radiographical tumor assessments by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
• 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 ]
  Physical exam abnormalities as as graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 26, 2022)

• Part 1 and Part 2: ORR [ Time Frame: Baseline to 2 years ]
  ORR as assessed using the RECIST version 1.1.
• Part 1/2/3: Intracranial response [ Time Frame: Baseline to 2 years ]
  Intracranial response by RECIST version 1.1 (for brain metastases) & Response Assessment in Neuro-Oncology (RANO) - for primary brain tumors).
• Part 1 and Part 2: Duration of response [ Time Frame: Baseline to 2 years ]
  Duration of response
• Part 3: Number of participants with treatment-emergent adverse events (AEs) [ Time Frame: Baseline to 2 years ]
  AEs as characterized by type, frequency, severity, timing, seriousness, and relationship to study therapy
• Part 3: Number of participants with clinically significant change from baseline in laboratory abnormalities [ Time Frame: Baseline to 2 years ]
  Laboratory abnormalities as characterized by type, frequency, severity, and timing
• Part 3: Number of participants with clinically significant change from baseline in vital sign abnormalities [ Time Frame: Baseline to 2 years ]
  Vital sign abnormalities as characterized by type, frequency, severity, and timing
• Part 3: Dose interruptions due to AEs [ Time Frame: Baseline to 2 years ]
  Incidence of dose interruptions due to AEs
• Part 3: Dose dose modifications due to AEs [ Time Frame: Baseline to 2 years ]
  Incidence of dose modifications due to AEs
• Part 3: Discontinuations due to AEs [ Time Frame: Baseline to 2 years ]
  Incidence of discontinuations due to AEs
• Part 3: Time to event endpoints in each combination [ Time Frame: Baseline to 2 years ]
  Time to event endpoints in each combination
• Part 3: Disease Control Rate (DCR) [ Time Frame: Baseline to 2 years ]
  DCR
• Part 1/2/3: PK parameters of PF-07799933, Single dose, maximum observed concentration (Cmax) [ Time Frame: Baseline to 2 years ]
  PK parameters of PF-07799933, Single dose, Cmax
• Part 1/2/3: PK parameters of PF-07799933, Single dose, time to maximum plasma concentration (Tmax) [ Time Frame: Baseline to 2 years ]
  PK parameters of PF-07799933, Single dose, Tmax
• 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) [ Time Frame: Baseline to 2 years ]
  PK parameters of PF-07799933, Single dose, AUClast
• Part 1/2/3: PK parameters of PF-07799933, Single dose, area under plasma concentration-time curve over 24 hours (AUC24) [ Time Frame: Baseline to 2 years ]
  PK parameters of PF-07799933, Single dose, AUC24
• Part 1/2/3: PK parameters of PF-07799933, Single dose, area under plasma concentration-time curve over 48 hours (AUC48) [ Time Frame: Baseline to 2 years ]
  PK parameters of PF-07799933, Single dose, AUC48
• Part 1/2/3: PK parameters of PF-07799933, Single dose, terminal elimination half life (t½) [ Time Frame: Baseline to 2 years ]
  PK parameters of PF-07799933, Single dose, t½
• 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) [ Time Frame: Baseline to 2 years ]
  PK parameters of PF-07799933, Single dose, AUCinf
• Part 1/2/3: PK parameters of PF-07799933, Single dose, apparent oral clearance (CL/F) [ Time Frame: Baseline to 2 years ]
  PK parameters of PF-07799933, Single dose, CL/F
• Part 1/2/3: PK parameters of PF-07799933, Single dose, apparent volume of distribution (Vz/F) [ Time Frame: Baseline to 2 years ]
  PK parameters of PF-07799933, Single dose, Vz/F
• Part 1/2/3: PK parameters of PF-07799933, Multiple dose, maximum observed concentration (Cmax) [ Time Frame: Baseline to 2 years ]
  PK parameters of PF-07799933, Multiple dose, Cmax
• Part 1/2/3: PK parameters of PF-07799933, Multiple dose, trough plasma or serum concentration (Ctrough) [ Time Frame: Baseline to 2 years ]
  PK parameters of PF-07799933, Multiple dose, Ctrough
• Part 1/2/3: PK parameters of PF-07799933, Multiple dose, time to maximum plasma concentration (Tmax) [ Time Frame: Baseline to 2 years ]
  PK parameters of PF-07799933, Multiple dose, Tmax
• Part 1/2/3: PK parameters of PF-07799933, Multiple dose, area under the plasma concentration-time curve over the dosing interval (AUCτ) [ Time Frame: Baseline to 2 years ]
  PK parameters of PF-07799933, Multiple dose, AUCτ
• Part 1/2/3: PK parameters of PF-07799933, Multiple dose, CL/F [ Time Frame: Baseline to 2 years ]
  PK parameters of PF-07799933, Multiple dose, CL/F
• Part 1/2/3: PK parameters of PF-07799933, Multiple dose, average plasma concentration (Cav) [ Time Frame: Baseline to 2 years ]
  PK parameters of PF-07799933, Multiple dose, Cav
• Part 1/2/3: PK parameters of PF-07799933, Multiple dose, peak-to-trough ratio (PTR) [ Time Frame: Baseline to 2 years ]
  PK parameters of PF-07799933, Multiple dose, PTR
• Part 1/2/3: PK parameters of PF-07799933, Multiple dose, accumulation ratio (Rac) [ Time Frame: Baseline to 2 years ]
  PK parameters of PF-07799933, Multiple dose, Rac (AUCτ /AUCsd,τ)
• Part 1/2/3: PK parameters of PF-07799933, Multiple dose, t1/2 [ Time Frame: Baseline to 2 years ]
  PK parameters of PF-07799933, Multiple dose, t1/2
• Part 1/2/3: PK parameters of PF-07799933, Multiple dose, Vz/F [ Time Frame: Baseline to 2 years ]
  PK parameters of PF-07799933, Multiple dose, Vz/F
• Part 3: PK parameters of cytochrome P450 (CYP)3A4 probe substrate midazolam, Cmax [ Time Frame: Baseline to 2 years ]
  PK parameters of CYP3A4 probe substrate midazolam, Cmax
• Part 3: PK parameters of CYP3A4 probe substrate midazolam, Tmax [ Time Frame: Baseline to 2 years ]
  PK parameters of CYP3A4 probe substrate midazolam, Tmax
• Part 3: PK parameters of CYP3A4 probe substrate midazolam, AUClast [ Time Frame: Baseline to 2 years ]
  PK parameters of CYP3A4 probe substrate midazolam, AUClast
• Part 3: PK parameters of CYP3A4 probe substrate midazolam, t½ [ Time Frame: Baseline to 2 years ]
  PK parameters of CYP3A4 probe substrate midazolam, t½
• Part 3: PK parameters of CYP3A4 probe substrate midazolam, AUCinf [ Time Frame: Baseline to 2 years ]
  PK parameters of CYP3A4 probe substrate midazolam, AUCinf
• Part 3: PK parameters of CYP3A4 probe substrate midazolam, CL/F [ Time Frame: Baseline to 2 years ]
  PK parameters of CYP3A4 probe substrate midazolam, CL/F
• Part 3: PK parameters of CYP3A4 probe substrate midazolam, Vz/F [ Time Frame: Baseline to 2 years ]
  PK parameters of CYP3A4 probe substrate midazolam, Vz/F
• Part 3: TTR [ Time Frame: Baseline to 2 years ]
  Time to response (TTR)
• Part 3: DOR [ Time Frame: Baseline to 2 years ]
  Duration of response (DOR)
• Part 3: PFS [ Time Frame: Baseline to 2 years ]
  Progression-free survival (PFS)
• Part 3: OS [ Time Frame: Baseline to 2 years ]
  Overall survival (OS)
• Number of participants with clinically significant physical exam abnormalities (Part 3) [ Time Frame: Baseline to 28 days after last dose of study medication ]
  Physical exam abnormalities as as graded by NCI CTCAE version 5.0

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

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

Intervention

• Drug: PF-07799933
  Tablet
  Other Name: ARRY-440
• Drug: binimetinib
  Tablet
  Other Name: Mektovi, PF-06811462, MEK162
• Biological: cetuximab
  Injection for intravenous use
  Other Name: Erbitux

Study Arms

• Experimental: Monotherapy dose escalation (Part 1)
  Participants will receive PF-07799933
  Intervention: Drug: PF-07799933
• Experimental: Combination dose escalation (Part 2)
  Participants will receive PF-07799933 in combination with binimetinib or cetuximab
  Interventions:

  • Drug: PF-07799933
  • Drug: binimetinib
  • Biological: cetuximab
• Experimental: Dose expansion (Part 3) - Tumor and mutation specific Cohort 1
  Participants will receive PF-07799933
  Intervention: Drug: PF-07799933
• Experimental: Dose expansion (Part 3) - Tumor and mutation specific Cohort 2
  Participants will receive PF-07799933
  Interventions:

  • Drug: PF-07799933
  • Drug: binimetinib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 29, 2024): 156
• Original Estimated Enrollment (submitted: April 26, 2022): 174
• Estimated Study Completion Date: January 29, 2029
• Estimated Primary Completion Date: July 29, 2027 (Final data collection date for primary outcome measure)

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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 16 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Pfizer CT.gov Call Center; 1-800-718-1021; ClinicalTrials.gov_Inquiries@pfizer.com

• Listed Location Countries: Canada, Israel, United States

Administrative Information

• NCT Number: NCT05355701
• Other Study ID Numbers: C4761001; BRAF Class 2 ( Other Identifier: Alias Study Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No
• 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.

• Current Responsible Party: Pfizer
• Original Responsible Party: Same as current
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: April 2024