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NCT Number: NCT05355701

A Study to Learn About the Study Medicine Called PF-07799933 in People 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 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.

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Key information

Conditions

Melanoma Advanced Colorectal Cancer (Part 1) Bronchial Neoplasms Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Endocrine Gland Neoplasms Endocrine System Diseases Glioma Head and Neck Neoplasms Lung Diseases Lung Neoplasms Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neoplasms, Neuroepithelial Neuroectodermal Tumors Neuroendocrine Tumors Nevi and Melanomas Non-Small-Cell Lung Cancer Respiratory Tract Diseases Respiratory Tract Neoplasms Skin Diseases Skin Neoplasms Skin and Connective Tissue Diseases Thoracic Neoplasms Thyroid Cancer Thyroid Diseases Thyroid Neoplasms

Age range

16 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

The Ottawa Hospital - General Campus, Ottawa, Ontario, Canada

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Exclusion criteria

  • 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).

Treatment and study plan

PF-07799933

Drug

Tablet

Other names: ARRY-440

Binimetinib

Drug

Tablet

Other names: Mektovi, PF-06811462, MEK162

Cetuximab

Biological

Injection for intravenous use

Other names: Erbitux

midazolam

Drug

syrup

Fluorouracil

Drug

Injection for intravenous use

Leucovorin

Drug

Injection for intravenous use

Oxaliplatin

Drug

Injection for intravenous use

Primary outcomes

  1. 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

  2. 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

  3. 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

  4. 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

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

    Time frame: Baseline to 2 years

    Incidence of dose interruptions due to AEs

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

    Time frame: Baseline to 2 years

    Incidence of dose modifications due to AEs

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

    Time frame: Baseline to 2 years

    Incidence of discontinuations due to AEs

  8. 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)

  9. 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

Secondary outcomes

  1. Part 1 and Part 2: ORR

    Time frame: Baseline to 2 years

    ORR as assessed using the RECIST version 1.1.

  2. 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).

  3. Part 1 and Part 2: Duration of response

    Time frame: Baseline to 2 years

    Duration of response

  4. 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

  5. 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

  6. 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

  7. Part 3: Dose interruptions due to AEs

    Time frame: Baseline to 2 years

    Incidence of dose interruptions due to AEs

  8. Part 3: Dose dose modifications due to AEs

    Time frame: Baseline to 2 years

    Incidence of dose modifications due to AEs

  9. Part 3: Discontinuations due to AEs

    Time frame: Baseline to 2 years

    Incidence of discontinuations due to AEs

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

    Time frame: Baseline to 2 years

    Time to event endpoints in each combination

  11. Part 3: Disease Control Rate (DCR)

    Time frame: Baseline to 2 years

    DCR

  12. 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

  13. 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

  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)

    Time frame: 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)

    Time frame: 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)

    Time frame: 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)

    Time frame: 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)

    Time frame: 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)

    Time frame: 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)

    Time frame: 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)

    Time frame: 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)

    Time frame: 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)

    Time frame: 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)

    Time frame: 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

    Time frame: Baseline to 2 years

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

  26. 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

  27. 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

  28. 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)

  29. 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

  30. 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

  31. 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

  32. Part 3: PK parameters of CYP3A4 probe substrate midazolam, Tmax

    Time frame: Baseline to 2 years

    PK parameters of CYP3A4 probe substrate midazolam, Tmax

  33. Part 3: PK parameters of CYP3A4 probe substrate midazolam, AUClast

    Time frame: Baseline to 2 years

    PK parameters of CYP3A4 probe substrate midazolam, AUClast

  34. Part 3: PK parameters of CYP3A4 probe substrate midazolam, t½

    Time frame: Baseline to 2 years

    PK parameters of CYP3A4 probe substrate midazolam, t½

  35. Part 3: PK parameters of CYP3A4 probe substrate midazolam, AUCinf

    Time frame: Baseline to 2 years

    PK parameters of CYP3A4 probe substrate midazolam, AUCinf

  36. 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

  37. 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

  38. Part 3: TTR

    Time frame: Baseline to 2 years

    Time to response (TTR)

  39. Part 3: DOR

    Time frame: Baseline to 2 years

    Duration of response (DOR)

  40. Part 3: PFS

    Time frame: Baseline to 2 years

    Progression-free survival (PFS)

  41. Part 3: OS

    Time frame: Baseline to 2 years

    Overall survival (OS)

  42. 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

Study contacts

Contact information is provided by the study sponsor or research team.

Pfizer CT.gov Call Center

CONTACT

[email protected]

1-800-718-1021

Sponsors and collaborators

Lead sponsor

Pfizer

Industry

Registry information

Official study 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

Important dates

Study start
2022
Primary completion
2028
Study completion
2029
First posted
May 2, 2022
Registry last updated
Jul 9, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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