Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Nervous System Diseases

Rare Diseases

Carcinoma

Melanoma

Carcinoma, Non-Small-Cell Lung

Brain Neoplasms

Brain Diseases

Central Nervous System Neoplasms

Nervous System Neoplasms

Neoplasms by Histologic Type

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Central Nervous System Diseases

Neuroendocrine Tumor

Neuroepithelioma

Adjuvants, Anesthesia

Central Nervous System Depressants

Psychotropic Drugs

All Drugs and Chemicals

Midazolam

Enzyme Inhibitors

Anesthetics

Hypnotics and Sedatives

Anti-Anxiety Agents

Anesthetics, Intravenous

Anesthetics, General

GABA Modulators

Neurotransmitter Agents

Monotherapy dose escalation of PF-07284890

Combination dose escalation of PF-07284890 + binimetinib

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

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

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

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

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

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

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

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

PF-07284890

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

Binimetinib

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

Pfizer CT.gov Call Center

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.

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

A TWO-PART, PHASE 1A/B, OPEN-LABEL, MULTICENTER TRIAL EVALUATING PHARMACOKINETICS, SAFETY AND EFFICACY OF PF 07284890 (ARRY 461) IN PARTICIPANTS WITH BRAF V600 MUTANT SOLID TUMORS WITH AND WITHOUT BRAIN INVOLVEMENT

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

DLTs will be evaluated during the first cycle (21 days) as both a single agent or in combination with binimetinib. The number of DLTs will be used to determine the maximum tolerated dose (MTD)/recommended dose for further study

AEs as characterized by type, frequency, severity, timing, seriousness, and relationship to study therapy

Laboratory abnormalities as characterized by type, frequency, severity, and timing

Incidence of dose interruptions, dose modifications, and discontinuations due to AEs

Response will be evaluated via radiographical tumor assessments by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and intracranial response by modified RECIST version 1.1 (mRECIST v 1.1) or RANO for primary brain tumors

Single dose (Cmax) and multiple dose (assuming steady state is achieved; Css,max) pharmacokinetic (PK) parameters

Single dose (Tmax) and multiple dose (assuming steady state is achieved; Tss,max) PK parameters

Single dose and multiple dose (assuming steady state is achieved and data permit) PK parameter

Single dose will be calculated as data permit PK parameter

Single dose (CL/F) and multiple dose (assuming steady state is achieved and as data permit; CLss/F) PK parameter

Single dose (Vz/F) and multiple dose (assuming steady state is achieved and as data permit; Vss/F) PK parameter

Multiple dose (assuming steady state is achieved) PK parameter

Multiple dose (assuming steady state is achieved and as data permit) PK parameter

Response will be evaluated via radiographical tumor assessments by RECIST v1.1 and intracranial response by mRECIST v 1.1 or RANO for primary brain tumors

Single dose (Cmax) and multiple dose (assuming steady state is achieved; Css,max) PK parameter

Single dose (Tmax) and multiple dose (assuming steady state is achieved; Tss,max) PK parameter

DCR is defined as the percent of participants with a confirmed complete response (CR), partial response (PR) or stable disease (SD) according to RECIST 1.1/RANO, at 6 weeks for both overall and intracranial

The period from study entry until disease progression, death or date of last contact for both overall and intracranial.

Overall survival was the duration from enrollment to death. For participants who are alive, overall survival was censored at the last contact.

Duration of response (DR) defined as time from start of first documented objective tumor response \[Complete Response (CR) or Partial Response (PR)\] to first documented objective tumor progression or death due to any cause, whichever occurs first.

TTR is defined as the time from first dose to first documentation of objective tumor response (CR or PR). For participants whose objective response (OR) proceeds from PR to CR, the onset of PR is taken as the onset of response. TTR will only be calculated for the subgroup of participants with a confirmed objective tumor response for both overall and intracranial

Spots Global Cancer Trial Database for brain neoplasms, primary