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Purpose

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.

Conditions

Eligibility

Eligible Ages
Over 16 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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).

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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
  • 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
  • Drug: midazolam
    syrup
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 and mFOLFOX6 regimen
  • Drug: PF-07799933
    Tablet
    Other names:
    • ARRY-440
  • Biological: cetuximab
    Injection for intravenous use
    Other names:
    • Erbitux
  • Drug: fluorouracil
    Injection for intravenous use
  • Drug: leucovorin
    Injection for intravenous use
  • Drug: oxaliplatin
    Injection for intravenous use
Experimental
Dose expansion (Part 3) - Tumor and mutation specific Cohort 6 		Participants will receive PF-07799933
  • Drug: PF-07799933
    Tablet
    Other names:
    • ARRY-440
Experimental
Dose expansion (Part 3) - Tumor and mutation specific Cohort 7 		Participants will receive PF-07799933
  • Drug: PF-07799933
    Tablet
    Other names:
    • ARRY-440

Recruiting Locations

Brigham and Women's Hospital
Boston 4930956, Massachusetts 6254926 02115

More Details

Status
Recruiting
Sponsor
Pfizer

Study Contact

Pfizer CT.gov Call Center
1-800-718-1021
ClinicalTrials.gov_Inquiries@pfizer.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.