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

NCT05355701
clinicaltrials.gov
Phase
Phase 1
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Recruitment status
Recruiting
clinicaltrials.gov
Participants
267
clinicaltrials.gov
Lead sponsor
Pfizer
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Start date
2022-07-05
clinicaltrials.gov
Number of sites
40
clinicaltrials.gov

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

Control arm
Open label
clinicaltrials.gov
Registry reports results
No
clinicaltrials.gov
Listing at source
Listed
clinicaltrials.gov
Recruitment status
Recruiting
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Phase
Phase 1
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Study type
Interventional
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Completion date
2029-10-25
clinicaltrials.gov
First posted
2022-05-02
clinicaltrials.gov
Registry last updated
2026-07-31
clinicaltrials.gov
Primary completion date
2028-04-23
clinicaltrials.gov
Start date
2022-07-05
clinicaltrials.gov

Participants
267
clinicaltrials.gov
Participant count basis
Estimated
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Planned participants
267
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Protocol amendments
5
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Number of sites
40
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Data monitoring committee
No
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Registry sponsor category
Industry
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Lead sponsor
Pfizer
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Source registry
ClinicalTrials.gov
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Registry ID
NCT05355701
clinicaltrials.gov
ClinicalTrials.gov ID
NCT05355701
clinicaltrials.gov
Registry record
Open registry record
clinicaltrials.gov

Allocation
Not randomised
Model
Sequential
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  1. Number of participants with dose limiting toxicities (DLTs) (Part 1 and Part 2)

    Timeframe: 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

  2. 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

    AEs as characterized by type, frequency, severity, timing, seriousness, and relationship to study therapy

  3. 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

    Laboratory abnormalities as characterized by type, frequency, severity, and timing

  4. 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

    Vital sign abnormalities as characterized by type, frequency, severity, and timing

  5. Dose interruptions due to AEs (Part 1 and Part 2)

    Timeframe: Baseline to 2 years

    Incidence of dose interruptions due to AEs

  6. Dose dose modifications due to AEs (Part 1 and Part 2)

    Timeframe: Baseline to 2 years

    Incidence of dose modifications due to AEs

  7. Discontinuations due to AEs (Part 1 and Part 2)

    Timeframe: Baseline to 2 years

    Incidence of discontinuations due to AEs

  8. Overall response rate (ORR) (Part 3)

    Timeframe: 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)

  9. 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

    Physical exam abnormalities as as graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

  1. Part 1 and Part 2: ORR

    Timeframe: Baseline to 2 years

    ORR as assessed using the RECIST version 1.1.

  2. Part 1/2/3: Intracranial response

    Timeframe: Baseline to 2 years

    Intracranial response by RECIST version 1.1 (for brain metastases) \& Response Assessment in Neuro-Oncology (RANO) - for primary brain tumors).

  3. Part 1 and Part 2: Duration of response

    Timeframe: Baseline to 2 years

    Duration of response

  4. Part 3: Number of participants with treatment-emergent adverse events (AEs)

    Timeframe: Baseline to 2 years

    AEs as characterized by type, frequency, severity, timing, seriousness, and relationship to study therapy

  5. Part 3: Number of participants with clinically significant change from baseline in laboratory abnormalities

    Timeframe: Baseline to 2 years

    Laboratory abnormalities as characterized by type, frequency, severity, and timing

  6. Part 3: Number of participants with clinically significant change from baseline in vital sign abnormalities

    Timeframe: Baseline to 2 years

    Vital sign abnormalities as characterized by type, frequency, severity, and timing

  7. Part 3: Dose interruptions due to AEs

    Timeframe: Baseline to 2 years

    Incidence of dose interruptions due to AEs

  8. Part 3: Dose dose modifications due to AEs

    Timeframe: Baseline to 2 years

    Incidence of dose modifications due to AEs

  9. Part 3: Discontinuations due to AEs

    Timeframe: Baseline to 2 years

    Incidence of discontinuations due to AEs

  10. Part 3: Time to event endpoints in each combination

    Timeframe: Baseline to 2 years

    Time to event endpoints in each combination

  11. Part 3: Disease Control Rate (DCR)

    Timeframe: Baseline to 2 years

    DCR

  12. Part 1/2/3: PK parameters of PF-07799933, Single dose, maximum observed concentration (Cmax)

    Timeframe: Baseline to 2 years

    PK parameters of PF-07799933, Single dose, Cmax

  13. Part 1/2/3: PK parameters of PF-07799933, Single dose, time to maximum plasma concentration (Tmax)

    Timeframe: Baseline to 2 years

    PK parameters of PF-07799933, Single dose, Tmax

  14. 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

    PK parameters of PF-07799933, Single dose, AUClast

  15. 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

    PK parameters of PF-07799933, Single dose, AUC24

  16. 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

    PK parameters of PF-07799933, Single dose, AUC48

  17. Part 1/2/3: PK parameters of PF-07799933, Single dose, terminal elimination half life (t½)

    Timeframe: Baseline to 2 years

    PK parameters of PF-07799933, Single dose, t½

  18. 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

    PK parameters of PF-07799933, Single dose, AUCinf

  19. Part 1/2/3: PK parameters of PF-07799933, Single dose, apparent oral clearance (CL/F)

    Timeframe: Baseline to 2 years

    PK parameters of PF-07799933, Single dose, CL/F

  20. Part 1/2/3: PK parameters of PF-07799933, Single dose, apparent volume of distribution (Vz/F)

    Timeframe: Baseline to 2 years

    PK parameters of PF-07799933, Single dose, Vz/F

  21. Part 1/2/3: PK parameters of PF-07799933, Multiple dose, maximum observed concentration (Cmax)

    Timeframe: Baseline to 2 years

    PK parameters of PF-07799933, Multiple dose, Cmax

  22. Part 1/2/3: PK parameters of PF-07799933, Multiple dose, trough plasma or serum concentration (Ctrough)

    Timeframe: Baseline to 2 years

    PK parameters of PF-07799933, Multiple dose, Ctrough

  23. Part 1/2/3: PK parameters of PF-07799933, Multiple dose, time to maximum plasma concentration (Tmax)

    Timeframe: Baseline to 2 years

    PK parameters of PF-07799933, Multiple dose, Tmax

  24. 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

    PK parameters of PF-07799933, Multiple dose, AUCτ

  25. Part 1/2/3: PK parameters of PF-07799933, Multiple dose, CL/F

    Timeframe: Baseline to 2 years

    PK parameters of PF-07799933, Multiple dose, CL/F

And 17 more, listed on the interactive page.

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Children, Adults, Older adults
Minimum age
16 Years
Healthy volunteers
No

This study is seeking participants who meet the following key eligibility 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.

  • 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).
Sources for eligibility
clinicaltrials.gov

  • Highlands Oncology Group, PAFayetteville, United StatesRecruiting
  • Highlands Oncology Group, PARogers, United StatesRecruiting
  • Highlands Oncology Group, PASpringdale, United StatesRecruiting
  • Clinical and Translational Research Center (CTRC)Aurora, United StatesRecruiting
  • UCHealth Sue Anschutz-Rodgers Eye CenterAurora, United StatesRecruiting
  • University of Colorado Hospital - Anschutz Cancer Pavilion (ACP)Aurora, United StatesRecruiting
  • University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP)Aurora, United StatesRecruiting
  • University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP)Aurora, United StatesRecruiting
  • Sylvester Comprehensive Cancer CenterMiami, United StatesRecruiting
  • University of Miami Hospital and ClinicsMiami, United StatesRecruiting
  • Brigham and Women's HospitalBoston, United StatesRecruiting
  • Dana-Farber Cancer InstituteBoston, United StatesRecruiting
  • Dana-Farber Cancer Institute - Chestnut HillNewton, United StatesRecruiting
  • Brigitte Harris Cancer PavilionDetroit, United StatesRecruiting
  • Henry Ford Cancer - Detroit (Brigitte Harris Cancer Pavilion)Detroit, United StatesRecruiting
  • Henry Ford Medical Center - ColumbusNovi, United StatesRecruiting
  • CT Scan and Echo Only: Henry Ford Medical Center-PlymouthPlymouth, United StatesRecruiting
  • MSK MonmouthMiddletown, United StatesRecruiting
  • MSK David H. Koch Center for Cancer CareNew York, United StatesRecruiting
  • Memorial Sloan Kettering Cancer Center 53rd streetNew York, United StatesRecruiting
  • Memorial Sloan Kettering Cancer CenterNew York, United StatesRecruiting
  • Cleveland Clinic Taussig Cancer Center Investigational PharmacyCleveland, United StatesRecruiting
  • Cleveland ClinicCleveland, United StatesRecruiting
  • Providence Cancer Institute Franz ClinicPortland, United StatesRecruiting
  • Providence Portland Medical CenterPortland, United StatesRecruiting

And 15 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

Sources for references
clinicaltrials.gov

Related records

Drugs (7)

Lead sponsors (1)

Conditions (6)

Targets (20)