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MelanomaPhase 1NCT05355701

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

A Phase 1 study testing PF-07799933, binimetinib and cetuximab in people with Melanoma and Non-Small-Cell Lung Cancer, run by Pfizer at 40 sites in 3 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 16 years and older
What is being tested?
PF-07799933, binimetinib and cetuximab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
103 participants
Where
40 sitesin 3 countries
Study dates
5 Jul 2022to 31 Aug 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 16 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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).

Trial locations and contacts

40 sites in 3 countries.

40 sites in 3 countries

United States31 sites

  • Clinical and Translational Research Center (CTRC)

    Aurora, Colorado, 80045

  • UCHealth Sue Anschutz-Rodgers Eye Center

    Aurora, Colorado, 80045

  • University of Colorado Hospital - Anschutz Cancer Pavilion (ACP)

    Aurora, Colorado, 80045

  • University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP)

    Aurora, Colorado, 80045

  • University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP)

    Aurora, Colorado, 80045

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Cleveland Clinic Taussig Cancer Center Investigational Pharmacy

    Cleveland, Ohio, 44106

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • Brigitte Harris Cancer Pavilion

    Detroit, Michigan, 48202

  • Henry Ford Cancer - Detroit (Brigitte Harris Cancer Pavilion)

    Detroit, Michigan, 48202

  • Highlands Oncology Group, PA

    Fayetteville, Arkansas, 72703

  • Sylvester Comprehensive Cancer Center

    Miami, Florida, 33136

  • University of Miami Hospital and Clinics

    Miami, Florida, 33136

  • MSK Monmouth

    Middletown, New Jersey, 07748

  • Sarah Cannon Research Institute - Pharmacy

    Nashville, Tennessee, 37203

  • SCRI Oncology Partners

    Nashville, Tennessee, 37203

  • TriStar Bone Marrow Transplant

    Nashville, Tennessee, 37203

  • TriStar Centennial Medical Center - Cell Processing Lab

    Nashville, Tennessee, 37203

  • TriStar Centennial Medical center

    Nashville, Tennessee, 37203

  • MSK David H. Koch Center for Cancer Care

    New York, New York, 10021

  • Memorial Sloan Kettering Cancer Center 53rd street

    New York, New York, 10022

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Dana-Farber Cancer Institute - Chestnut Hill

    Newton, Massachusetts, 02467

  • Henry Ford Medical Center - Columbus

    Novi, Michigan, 48377

  • CT Scan and Echo Only: Henry Ford Medical Center-Plymouth

    Plymouth, Michigan, 48170

  • Providence Cancer Institute Franz Clinic

    Portland, Oregon, 97213

  • Providence Portland Medical Center

    Portland, Oregon, 97213

  • Highlands Oncology Group, PA

    Rogers, Arkansas, 72758

  • START San Antonio

    San Antonio, Texas, 78229

  • Highlands Oncology Group, PA

    Springdale, Arkansas, 72762

Other trials in United States

Canada5 sites

  • Jewish General Hospital

    Montreal, Quebec, H3T 1E2

  • McGill University Health Centre

    Montreal, Quebec, H4A 3J1

  • The Ottawa Hospital - General Campus

    Ottawa, Ontario, K1H 8L6

  • Princess Margaret Cancer Centre

    Toronto, Ontario, M5G 1X6

  • University Health Network

    Toronto, Ontario, M5G 2C4

Other trials in Canada

Israel4 sites

  • Rambam Health Care Campus

    Haifa, Ḥeifā, 3109601

  • Hadassah Medical Center

    Jerusalem, 9112001

  • Sheba Medical Center

    Ramat Gan, 5262000

  • Sourasky Medical Center

    Tel Aviv, Central District, 6423906

Other trials in Israel

About this study

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

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.

Read more

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.

Being tested
PF-07799933, binimetinib, cetuximab, midazolam, fluorouracil
Medical subject headings
Melanoma, Carcinoma, Non-Small-Cell Lung, Thyroid Neoplasms, Glioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PF-07799933Drug

    Also called ARRY-440

    Tablet

  • binimetinibDrug

    Also called Mektovi, PF-06811462, MEK162

    Tablet

  • cetuximabBiological

    Also called Erbitux

    Injection for intravenous use

  • midazolamDrug

    syrup

  • fluorouracilDrug

    Injection for intravenous use

  • leucovorinDrug

    Injection for intravenous use

  • oxaliplatinDrug

    Injection for intravenous use

Study groups in NCT05355701
Study groupRoleWhat they receive
Monotherapy dose escalation (Part 1)ExperimentalParticipants will receive PF-07799933
Receives: Drug: PF-07799933
Combination dose escalation (Part 2)ExperimentalParticipants will receive PF-07799933 in combination with binimetinib or cetuximab
Receives: Drug: PF-07799933; Drug: binimetinib; Biological: cetuximab
Dose expansion (Part 3) - Tumor and mutation specific Cohort 1ExperimentalParticipants will receive PF-07799933
Receives: Drug: PF-07799933
Dose expansion (Part 3) - Tumor and mutation specific Cohort 2ExperimentalParticipants will receive PF-07799933
Receives: Drug: PF-07799933; Drug: binimetinib
Dose expansion (Part 3) - Tumor and mutation specific Cohort 3ExperimentalParticipants will receive PF-07799933
Receives: Drug: PF-07799933; Drug: midazolam
Dose expansion (Part 3) - Tumor and mutation specific Cohort 4ExperimentalParticipants will receive PF-07799933 in combination with cetuximab
Receives: Drug: PF-07799933; Biological: cetuximab
Dose expansion (Part 3) - Tumor and mutation specific Cohort 5ExperimentalParticipants will receive PF-07799933 in combination with cetuximab and mFOLFOX6 regimen
Receives: Drug: PF-07799933; Biological: cetuximab; Drug: fluorouracil; Drug: leucovorin; Drug: oxaliplatin
Dose expansion (Part 3) - Tumor and mutation specific Cohort 6ExperimentalParticipants will receive PF-07799933
Receives: Drug: PF-07799933
Dose expansion (Part 3) - Tumor and mutation specific Cohort 7ExperimentalParticipants will receive PF-07799933
Receives: Drug: PF-07799933

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: Cycle 1 (21 days)

  2. 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

    Measured: Baseline to 28 days after last dose of study medication

  3. 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

    Measured: Baseline to 28 days after last dose of study treatment

  4. 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

    Measured: Baseline to 28 days after last dose of study treatment

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

    Incidence of dose interruptions due to AEs

    Measured: Baseline to 2 years

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

    Incidence of dose modifications due to AEs

    Measured: Baseline to 2 years

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

    Incidence of discontinuations due to AEs

    Measured: Baseline to 2 years

  8. 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)

    Measured: Baseline to 2 years

  9. 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

    Measured: Baseline to 28 days after last dose of study treatment

Secondary outcomes (42)

  1. Part 1 and Part 2: ORR

    ORR as assessed using the RECIST version 1.1.

    Measured: Baseline to 2 years

  2. 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).

    Measured: Baseline to 2 years

  3. Part 1 and Part 2: Duration of response

    Duration of response

    Measured: Baseline to 2 years

  4. 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

    Measured: Baseline to 2 years

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

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

    Measured: Baseline to 2 years

  6. 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

    Measured: Baseline to 2 years

  7. Part 3: Dose interruptions due to AEs

    Incidence of dose interruptions due to AEs

    Measured: Baseline to 2 years

  8. Part 3: Dose dose modifications due to AEs

    Incidence of dose modifications due to AEs

    Measured: Baseline to 2 years

  9. Part 3: Discontinuations due to AEs

    Incidence of discontinuations due to AEs

    Measured: Baseline to 2 years

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

    Time to event endpoints in each combination

    Measured: Baseline to 2 years

  11. Part 3: Disease Control Rate (DCR)

    DCR

    Measured: Baseline to 2 years

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

    PK parameters of PF-07799933, Single dose, Cmax

    Measured: Baseline to 2 years

  13. 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

    Measured: Baseline to 2 years

  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)

    PK parameters of PF-07799933, Single dose, AUClast

    Measured: Baseline to 2 years

  15. 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

    Measured: Baseline to 2 years

  16. 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

    Measured: Baseline to 2 years

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

    PK parameters of PF-07799933, Single dose, t½

    Measured: Baseline to 2 years

  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)

    PK parameters of PF-07799933, Single dose, AUCinf

    Measured: Baseline to 2 years

  19. 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

    Measured: Baseline to 2 years

  20. 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

    Measured: Baseline to 2 years

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

    PK parameters of PF-07799933, Multiple dose, Cmax

    Measured: Baseline to 2 years

  22. 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

    Measured: Baseline to 2 years

  23. 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

    Measured: Baseline to 2 years

  24. 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

    Measured: Baseline to 2 years

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

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

    Measured: Baseline to 2 years

  26. Part 1/2/3: PK parameters of PF-07799933, Multiple dose, average plasma concentration (Cav)

    PK parameters of PF-07799933, Multiple dose, Cav

    Measured: Baseline to 2 years

  27. Part 1/2/3: PK parameters of PF-07799933, Multiple dose, peak-to-trough ratio (PTR)

    PK parameters of PF-07799933, Multiple dose, PTR

    Measured: Baseline to 2 years

  28. 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)

    Measured: Baseline to 2 years

  29. Part 1/2/3: PK parameters of PF-07799933, Multiple dose, t1/2

    PK parameters of PF-07799933, Multiple dose, t1/2

    Measured: Baseline to 2 years

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

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

    Measured: Baseline to 2 years

  31. Part 3: PK parameters of cytochrome P450 (CYP)3A4 probe substrate midazolam, Cmax

    PK parameters of CYP3A4 probe substrate midazolam, Cmax

    Measured: Baseline to 2 years

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

    PK parameters of CYP3A4 probe substrate midazolam, Tmax

    Measured: Baseline to 2 years

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

    PK parameters of CYP3A4 probe substrate midazolam, AUClast

    Measured: Baseline to 2 years

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

    PK parameters of CYP3A4 probe substrate midazolam, t½

    Measured: Baseline to 2 years

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

    PK parameters of CYP3A4 probe substrate midazolam, AUCinf

    Measured: Baseline to 2 years

  36. Part 3: PK parameters of CYP3A4 probe substrate midazolam, CL/F

    PK parameters of CYP3A4 probe substrate midazolam, CL/F

    Measured: Baseline to 2 years

  37. Part 3: PK parameters of CYP3A4 probe substrate midazolam, Vz/F

    PK parameters of CYP3A4 probe substrate midazolam, Vz/F

    Measured: Baseline to 2 years

  38. Part 3: TTR

    Time to response (TTR)

    Measured: Baseline to 2 years

  39. Part 3: DOR

    Duration of response (DOR)

    Measured: Baseline to 2 years

  40. Part 3: PFS

    Progression-free survival (PFS)

    Measured: Baseline to 2 years

  41. Part 3: OS

    Overall survival (OS)

    Measured: Baseline to 2 years

  42. Number of participants with clinically significant physical exam abnormalities (Part 3)

    Physical exam abnormalities as as graded by NCI CTCAE version 5.0

    Measured: Baseline to 28 days after last dose of study medication

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 May 2022
  2. Study start5 Jul 2022
  3. Primary completion31 Aug 2027 (estimated)
  4. Study completion31 Aug 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
103 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05355701
Sponsor's protocol ID
C4761001
Other IDs
BRAF Class 2
Status last verified
Aug 2026
First submitted
26 Apr 2022
Last updated
1 Sep 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: 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.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing PF-07799933, binimetinib and cetuximab in people with Melanoma and Non-Small-Cell Lung Cancer, run by Pfizer at 40 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 1 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 40 sites in United States, Canada, Israel. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of participants with dose limiting toxicities (DLTs) (Part 1 and Part 2) (time frame: Cycle 1 (21 days)). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05355701.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Sep 2026.

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