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

Sponsor
Pfizer (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05355701
Collaborator
(none)
174
Enrollment
7
Locations
8
Arms
59.7
Anticipated Duration (Months)
24.9
Patients Per Site
0.4
Patients Per Site Per Month

Study Details

Study Description

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 and cetuximab) 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, 1 or 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.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Anticipated Enrollment :
174 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Jul 5, 2022
Anticipated Primary Completion Date :
Dec 24, 2025
Anticipated Study Completion Date :
Jun 27, 2027

Arms and Interventions

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 in combination with binimetinib

    Drug: PF-07799933
    Tablet
    Other Names:
  • ARRY-440

    • Drug: binimetinib
    Tablet
    Other Names:
  • Mektovi, PF-06811462, MEK162

    		•
    Experimental: Dose expansion (Part 3) - Tumor and mutation specific Cohort 3

    Participants will receive PF-07799933

    Drug: PF-07799933
    Tablet
    Other Names:
  • ARRY-440

    		•
    Experimental: Dose expansion (Part 3) - Tumor and mutation specific Cohort 4

    Participants will receive PF-07799933 in combination with cetuximab

    Drug: PF-07799933
    Tablet
    Other Names:
  • ARRY-440

    • Biological: cetuximab
    Injection for intravenous use
    Other Names:
  • Erbitux

    		•
    Experimental: Dose expansion (Part 3) - Tumor and mutation specific Cohort 5

    Participants will receive PF-07799933 in combination with cetuximab

    Drug: PF-07799933
    Tablet
    Other Names:
  • ARRY-440

    • Biological: cetuximab
    Injection for intravenous use
    Other Names:
  • Erbitux

    		•
    Experimental: Dose expansion (Part 3) - Basket Cohort 6

    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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of participants with dose limiting toxicities (DLTs) (Part 1 and Part 2) [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) [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) [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) [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) [Baseline to 2 years]

      Incidence of dose interruptions due to AEs

    6. Dose dose modifications due to AEs (Part 1 and Part 2) [Baseline to 2 years]

      Incidence of dose modifications due to AEs

    7. Discontinuations due to AEs (Part 1 and Part 2) [Baseline to 2 years]

      Incidence of discontinuations due to AEs

    8. MTD (Part 1 and Part 2) [Cycle 1 (21 days)]

      Maximum tolerated dose (MTD)

    9. RDE (Part 1 and Part 2) [Cycle 1 (21 days)]

      Recommended dose for expansion (RDE)

    10. Overall response rate (ORR) (Part 3) [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)

    11. Number of participants with clinically significant physical exam abnormalities (Part 1 and Part 2) [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 Outcome Measures

    1. Part 1 and Part 2: ORR [Baseline to 2 years]

      ORR as assessed using the RECIST version 1.1.

    2. Part 1/2/3: Intracranial response [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 [Baseline to 2 years]

      Duration of response

    4. Part 3: Number of participants with treatment-emergent adverse events (AEs) [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 [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 [Baseline to 2 years]

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

    7. Part 3: Dose interruptions due to AEs [Baseline to 2 years]

      Incidence of dose interruptions due to AEs

    8. Part 3: Dose dose modifications due to AEs [Baseline to 2 years]

      Incidence of dose modifications due to AEs

    9. Part 3: Discontinuations due to AEs [Baseline to 2 years]

      Incidence of discontinuations due to AEs

    10. Part 3: Time to event endpoints in each combination [Baseline to 2 years]

      Time to event endpoints in each combination

    11. Part 3: Disease Control Rate (DCR) [Baseline to 2 years]

      DCR

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

      PK parameters of CYP3A4 probe substrate midazolam, Cmax

    32. Part 3: PK parameters of CYP3A4 probe substrate midazolam, Tmax [Baseline to 2 years]

      PK parameters of CYP3A4 probe substrate midazolam, Tmax

    33. Part 3: PK parameters of CYP3A4 probe substrate midazolam, AUClast [Baseline to 2 years]

      PK parameters of CYP3A4 probe substrate midazolam, AUClast

    34. Part 3: PK parameters of CYP3A4 probe substrate midazolam, t½ [Baseline to 2 years]

      PK parameters of CYP3A4 probe substrate midazolam, t½

    35. Part 3: PK parameters of CYP3A4 probe substrate midazolam, AUCinf [Baseline to 2 years]

      PK parameters of CYP3A4 probe substrate midazolam, AUCinf

    36. Part 3: PK parameters of CYP3A4 probe substrate midazolam, CL/F [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 [Baseline to 2 years]

      PK parameters of CYP3A4 probe substrate midazolam, Vz/F

    38. Part 3: TTR [Baseline to 2 years]

      Time to response (TTR)

    39. Part 3: DOR [Baseline to 2 years]

      Duration of response (DOR)

    40. Part 3: PFS [Baseline to 2 years]

      Progression-free survival (PFS)

    41. Part 3: OS [Baseline to 2 years]

      Overall survival (OS)

    42. Number of participants with clinically significant physical exam abnormalities (Part 3) [Baseline to 28 days after last dose of study medication]

      Physical exam abnormalities as as graded by NCI CTCAE version 5.0

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    16 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Highlands Oncology Group Springdale Arkansas United States 72762
    2 Sarah Cannon Research Institute - Pharmacy Nashville Tennessee United States 37203
    3 Tennessee Oncology PLLC Nashville Tennessee United States 37203
    4 Tennessee Oncology, PLLC Nashville Tennessee United States 37203
    5 TriStar Bone Marrow Transplant Nashville Tennessee United States 37203
    6 TriStar Centennial Medical Center - Cell Processing Lab Nashville Tennessee United States 37203
    7 TriStar Centennial Medical center Nashville Tennessee United States 37203

    Sponsors and Collaborators

    • Pfizer

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Pfizer
    ClinicalTrials.gov Identifier:
    NCT05355701
    Other Study ID Numbers:
    • C4761001
    • C4761001
    • BRAF Class 2
    First Posted:
    May 2, 2022
    Last Update Posted:
    Aug 9, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    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
    Additional relevant MeSH terms:
    Thyroid Neoplasms
    Cetuximab

    Study Results

    No Results Posted as of Aug 9, 2022