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

Pfizer

Status and phase: Enrolling; Phase 1

Conditions: Glioma; Advanced Colorectal Cancer (Part 1); Melanoma; Thyroid Cancer; Non-Small-Cell Lung Cancer

Treatments: Drug: fluorouracil; Drug: oxaliplatin; Biological: cetuximab; Drug: leucovorin; Drug: binimetinib; Drug: PF-07799933; Drug: midazolam

Study type: Interventional

Funder types: Industry

Identifiers

NCT05355701

BRAF Class 2 (Other Identifier)

C4761001 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 267 estimated patients

Sex: All

Ages: 16+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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).

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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267 participants in 9 patient groups

Monotherapy dose escalation (Part 1)

Experimental group

Description:

Participants will receive PF-07799933

Treatment:

Drug: PF-07799933

Combination dose escalation (Part 2)

Experimental group

Description:

Participants will receive PF-07799933 in combination with binimetinib or cetuximab

Treatment:

Drug: PF-07799933

Drug: binimetinib

Biological: cetuximab

Dose expansion (Part 3) - Tumor and mutation specific Cohort 1

Experimental group

Description:

Participants will receive PF-07799933

Treatment:

Drug: PF-07799933

Dose expansion (Part 3) - Tumor and mutation specific Cohort 2

Experimental group

Description:

Participants will receive PF-07799933

Treatment:

Drug: PF-07799933

Drug: binimetinib

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

Experimental group

Description:

Participants will receive PF-07799933

Treatment:

Drug: midazolam

Drug: PF-07799933

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

Experimental group

Description:

Participants will receive PF-07799933 in combination with cetuximab

Treatment:

Drug: PF-07799933

Biological: cetuximab

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

Experimental group

Description:

Participants will receive PF-07799933 in combination with cetuximab and mFOLFOX6 regimen

Treatment:

Drug: PF-07799933

Drug: leucovorin

Drug: oxaliplatin

Biological: cetuximab

Drug: fluorouracil

Dose expansion (Part 3) - Tumor and mutation specific Cohort 6

Experimental group

Description:

Participants will receive PF-07799933

Treatment:

Drug: PF-07799933

Dose expansion (Part 3) - Tumor and mutation specific Cohort 7

Experimental group

Description:

Participants will receive PF-07799933

Treatment:

Drug: PF-07799933