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

NCT ID: NCT04543188

Last Updated: 2025-10-23

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

65 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-01-08

Study Completion Date

2024-03-20

Brief Summary

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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.

Detailed Description

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Conditions

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Malignant Melanoma Carcinoma, Non-Small-Cell Lung Brain Neoplasms, Primary Brain Neoplasms Malignant Neoplasms

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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PF-07284890 (Part A monotherapy)

Monotherapy dose escalation of PF-07284890

Group Type EXPERIMENTAL

PF-07284890

Intervention Type DRUG

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

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

Combination dose escalation of PF-07284890 + binimetinib

Group Type EXPERIMENTAL

PF-07284890

Intervention Type DRUG

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

Binimetinib

Intervention Type DRUG

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

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

Group Type EXPERIMENTAL

PF-07284890

Intervention Type DRUG

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

Binimetinib

Intervention Type DRUG

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

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

Group Type EXPERIMENTAL

PF-07284890

Intervention Type DRUG

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

Binimetinib

Intervention Type DRUG

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

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

Group Type EXPERIMENTAL

PF-07284890

Intervention Type DRUG

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

Binimetinib

Intervention Type DRUG

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

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

Group Type EXPERIMENTAL

PF-07284890

Intervention Type DRUG

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

Binimetinib

Intervention Type DRUG

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

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

Group Type EXPERIMENTAL

PF-07284890

Intervention Type DRUG

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

Binimetinib

Intervention Type DRUG

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

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

Group Type EXPERIMENTAL

PF-07284890

Intervention Type DRUG

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

Binimetinib

Intervention Type DRUG

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

Midazolam

Intervention Type DRUG

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

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

Group Type EXPERIMENTAL

PF-07284890

Intervention Type DRUG

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

Binimetinib

Intervention Type DRUG

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

Interventions

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PF-07284890

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

Intervention Type DRUG

Binimetinib

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

Intervention Type DRUG

Midazolam

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

Intervention Type DRUG

Other Intervention Names

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ARRY-461 Mektovi

Eligibility Criteria

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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
Minimum Eligible Age

16 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Pfizer

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Pfizer CT.gov Call Center

Role: STUDY_DIRECTOR

Pfizer

Locations

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

Duarte, California, United States

Site Status

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

Site Status

Orlando Health Cancer Institute

Orlando, Florida, United States

Site Status

Moffitt Cancer Center

Tampa, Florida, United States

Site Status

Richard M Schulze Family Foundation Outpatient Center at McKinley Campus

Tampa, Florida, United States

Site Status

Northwestern Medical Group

Chicago, Illinois, United States

Site Status

Northwestern Memorial Hospital

Chicago, Illinois, United States

Site Status

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Site Status

Johns Hopkins University / Johns Hopkins Hospital

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Ophthalmic Consultants of Boston Inc (OCB)

Boston, Massachusetts, United States

Site Status

Brigham & Women's Hospital

Boston, Massachusetts, United States

Site Status

Imaging: Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Imaging: Brigham and Women's Radiology, Coolidge Corner Imaging

Brookline, Massachusetts, United States

Site Status

Imaging: Brigham and Women's Ambulatory Care

Chestnut Hill, Massachusetts, United States

Site Status

Imaging: Brigham and Women's Mass General Healthcare Center

Foxborough, Massachusetts, United States

Site Status

Dana-Farber Cancer Institute - Chestnut Hill

Newton, Massachusetts, United States

Site Status

Siteman Cancer Center - St Peters

City of Saint Peters, Missouri, United States

Site Status

Siteman Cancer Center - West County

Creve Coeur, Missouri, United States

Site Status

Siteman Cancer Center - North County

Florissant, Missouri, United States

Site Status

Barnes-Jewish Hospital

St Louis, Missouri, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Siteman Cancer Center - South County

St Louis, Missouri, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

MSK Monmouth.

Middletown, New Jersey, United States

Site Status

MSK Commack

Commack, New York, United States

Site Status

MSKCC-Westchester (500 Westchester Ave.)

Harrison, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center - David H. Koch Center for Cancer Care (74th Street).

New York, New York, United States

Site Status

Rockefeller Outpatient Pavilion (53rd Street)

New York, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

UNC Hospitals, The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

Duke Eye Center

Durham, North Carolina, United States

Site Status

Duke University Medical Center, Investigational Chemotherapy Services

Durham, North Carolina, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Tennessee Oncology PLLC

Franklin, Tennessee, United States

Site Status

Tennessee Oncology PLLC

Nashville, Tennessee, United States

Site Status

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Site Status

Rambam Health Care Campus

Haifa, ?eif?, Israel

Site Status

Rabin Medical Center

Petah Tikva, Central District, Israel

Site Status

Sheba Medical Center

Ramat Gan, Central District, Israel

Site Status

Hadassah Medical Center

Jerusalem, Jerusalem, Israel

Site Status

Sourasky Medical Center

Tel Aviv, TELL ABĪB, Israel

Site Status

Countries

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United States Canada Israel

References

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Ren L, Moreno D, Baer BR, Barbour P, Bettendorf T, Bouhana K, Brown K, Brown SA, Fell JB, Hartley DP, Hicken EJ, Laird ER, Lee P, McCown J, Otten JN, Prigaro B, Wallace R, Kahn D. Identification of the Clinical Candidate PF-07284890 (ARRY-461), a Highly Potent and Brain Penetrant BRAF Inhibitor for the Treatment of Cancer. J Med Chem. 2024 Aug 8;67(15):13019-13032. doi: 10.1021/acs.jmedchem.4c00998. Epub 2024 Jul 30.

Reference Type DERIVED
PMID: 39077892 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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https://pmiform.com/clinical-trial-info-request?StudyID=C4471001

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Other Identifiers

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2022-003184-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

C4471001

Identifier Type: -

Identifier Source: org_study_id

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