A FIH Study of PF-07284890 in Participants With BRAF V600 Mutant Solid Tumors With and Without Brain Involvement

Study Purpose

First-in-human study to assess safety, tolerability, PK, and preliminary activity of PF-07284890 as a single agent and in combination with binimetinib in participants with BRAF V600-mutated advanced solid tumor malignancies with and without brain involvement.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	16 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria:

- Age ≥16 years at the time of consent.

- Histologically confirmed diagnosis of advanced/metastatic solid tumor including primary brain tumor.

- Documented evidence of a BRAF V600 mutation in tumor tissue or blood.

- Confirmation of availability of adequate tumor tissue for submission to the sponsor/central laboratory.

- Presence or absence of brain involvement unless specified below.

- Dose Expansion (Part B) - Cohort 1, 2, 3, 4: melanoma with at least 1 parenchymal brain lesion.

- Cohort 1,3: asymptomatic in the brain for at least 14 days prior to start of study treatment.

- Cohort 2,4: symptomatic in the brain within 14 days prior to the start of study treatment.

- Cohort 5: any solid tumor that does not meet requirements for Cohorts 1-4, history of or current leptomeningeal metastases.

- Optional Cohort 6 (DDI Sub-study) and 7 (Food-Effect): if brain involvement present, must be asymptomatic.

- Disease progression despite prior treatment and no acceptable alternative treatment options available unless specified below.

- Dose Expansion (Part B) - Cohort 1, 2: No prior BRAF inhibitor in the metastatic setting or in the adjuvant setting within 6 months of study treatment.

- Cohort 3, 4: Required prior BRAF inhibitor in the metastatic setting or in the adjuvant setting within 6 months of treatment.

- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

Exclusion Criteria:

- Brain metastasis/primary brain tumor requiring immediate local intervention.

- History of or current leptomeningeal metastases.

- Any other active malignancy within 2 years prior to enrollment.

- Radiation therapy to visceral metastases within 14 days prior to study treatment.

WBRT within 28 days prior to study treatment.

- Systemic anti-cancer therapy or small-molecular therapeutic(s) within 2 weeks prior to start of study treatment; Antibody based agents within 4 weeks prior to start of study treatment.

- History or current evidence of RVO or current risk factors for RVO; History of retinal degenerative disease

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT04543188
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 1
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Pfizer
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Pfizer CT.gov Call Center
Principal Investigator Affiliation	Pfizer
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Industry
Overall Status	Terminated
Countries	Canada, Israel, United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Malignant Melanoma, Carcinoma, Non-Small-Cell Lung, Brain Neoplasms, Primary, Brain Neoplasms, Malignant Neoplasms
Study Website:	View Trial Website

Arms & Interventions

Arms

Experimental: PF-07284890 (Part A monotherapy)

Monotherapy dose escalation of PF-07284890

Experimental: PF-07284890+binimetinib (Part A combo-therapy)

Combination dose escalation of PF-07284890 + binimetinib

Experimental: Expansion Phase (Part B, Cohort 1)

PF-07284890 (at recommended dose from Part A) plus binimetinib in participants with BRAF V600 melanoma, with asymptomatic brain involvement, and no prior BRAF or MEK inhibitor utilization

Experimental: Expansion Phase (Part B, Cohort 2)

PF-07284890 (at recommended dose from Part A) plus binimetinib in participants with BRAF V600 melanoma, with symptomatic brain involvement, and no prior BRAF or MEK inhibitor utilization

Experimental: Expansion Phase (Part B, Cohort 3)

PF-07284890 (at recommended dose from Part A) plus binimetinib in participants with BRAF V600 melanoma, with asymptomatic brain involvement, and prior BRAF inhibitor utilization

Experimental: Expansion Phase (Part B, Cohort 4)

PF-07284890 (at recommended dose from Part A) plus binimetinib in participants with BRAF V600 melanoma, with symptomatic brain involvement, and prior BRAF inhibitor utilization

Experimental: Expansion Phase (Part B Cohort 5)

PF-07284890 (at recommended dose from Part A) plus binimetinib in participants with BRAF V600 solid tumor; history of or current leptomeningeal metastases; without disease in the brain; with disease in the brain that does not meet Cohorts 1-4; asymptomatic or symptomatic in the brain; primary brain tumors

Experimental: Expansion Phase Drug-Drug Interaction Substudy (Part B Optional Cohort 6)

PF-07284890 (at recommended dose from Part A) plus binimetinib plus midazolam in participants with BRAF V600 solid tumor

Experimental: Expansion Phase (Part B Optional Cohort 7)

PF-07284890 (at the recommended dose for expansion when administered with food) plus binimetinib in participants with BRAF V600 solid tumor

Interventions

Drug: - PF-07284890

PF-07284890 will be administered orally, daily for 21 consecutive days (21-day cycle)

Drug: - Binimetinib

Binimetinib will be administered together with PF-07284890 orally, 45mg twice daily

Drug: - Midazolam

Midazolam will be administered 7 days before start of study drug, on Cycle 1 Day 1, and on Cycle 1 Day 15

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Duarte, California

Status

Address

City of Hope (City of Hope National Medical Center, City of Hope Medical Center)

Duarte, California, 91010

Duarte, California

Status

Address

City of Hope Investigational Drug Services (IDS)

Duarte, California, 91010

Keck Hospital of USC, Los Angeles, California

Status

Address

Keck Hospital of USC