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

ConditionsMelanomaNon-Small-Cell Lung CancerThyroid CancerGliomaAdvanced Colorectal Cancer (Part 1)
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age16+
SponsorPfizer

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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 design

Design model

Sequential

Treatments tested in this trial

  • PF-07799933

    Drug

    Tablet

  • binimetinib

    Drug

    Tablet

  • cetuximab

    Biological/Vaccine

    Injection for intravenous use

  • midazolam

    Drug

    syrup

  • fluorouracil

    Drug

    Injection for intravenous use

  • leucovorin

    Drug

    Injection for intravenous use

  • oxaliplatin

    Drug

    Injection for intravenous use

Treatment groups

267 Participants
are divided into 9 treatment groups

9

Treatment groups

See each treatment group below.

Group A: Monotherapy dose escalation (Part 1)Experimental treatment 1 intervention
Group B: Combination dose escalation (Part 2)Experimental treatment 3 interventions
Group C: Dose expansion (Part 3) - Tumor and mutation specific Cohort 1Experimental treatment 1 intervention
Group D: Dose expansion (Part 3) - Tumor and mutation specific Cohort 2Experimental treatment 2 interventions
Group E: Dose expansion (Part 3) - Tumor and mutation specific Cohort 3Experimental treatment 2 interventions
Group F: Dose expansion (Part 3) - Tumor and mutation specific Cohort 4Experimental treatment 2 interventions
Group G: Dose expansion (Part 3) - Tumor and mutation specific Cohort 5Experimental treatment 5 interventions
Group H: Dose expansion (Part 3) - Tumor and mutation specific Cohort 6Experimental treatment 1 intervention
Group I: Dose expansion (Part 3) - Tumor and mutation specific Cohort 7Experimental treatment 1 intervention

Trial outcomes

Primary outcomes

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

Time frame
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

Time frame
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

Time frame
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

Time frame
Baseline to 28 days after last dose of study treatment

Secondary outcomes

1

Part 1 and Part 2: ORR

ORR as assessed using the RECIST version 1.1.

Time frame
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).

Time frame
Baseline to 2 years
3

Part 1 and Part 2: Duration of response

Duration of response

Time frame
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

Time frame
Baseline to 2 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Pfizer

Lead sponsor

Source ClinicalTrials.gov
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