PF-07284892 in Participants With Advanced Solid Tumors

Phase 1TerminatedNCT04800822

Pfizer53 enrolled

Overview

The purpose of this first-in-patient, open label study is to determine the maximum tolerated dose and/or recommended dose for further study of PF-07284892 as a single agent and in combination with lorlatinib, encorafenib and cetuximab, or binimetinib and evaluate the pharmacokinetics, safety, and preliminary clinical activity of single agent and each combination therapy.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Solid Tumor

Interventions

PF-07284892DRUG

PF-07284892

lorlatinibDRUG

lorlatinib

binimetinibDRUG

binimetinib

cetuximabBIOLOGICAL

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age ≥18 years at the time of informed consent * Histological or cytological diagnosis of ALK-positive advanced NSCLC, CRC with BRAF V600E mutation, or RAS- mutant, NF1-mutant or BRAF class 3 mutant solid tumor. Participants with ROS-positive NSCLC are also eligible for Part 1 and 2 (Other ROS1-positive solid tumors may be considered after discussion with the sponsor). * Documentation evidence of biomarker mutation status * Part 3: ALK-positive NSCLC with prior lorlatinib and no prior platinum-based chemotherapy (Cohort 1); with prior lorlatinib and prior platinum-based chemotherapy (Cohort 2); or with no prior lorlatinib (Cohort 3). BRAF V600E mutant CRC participants resistant to BRAFi plus EGFRi (Cohort 4 ); refractory to BRAFi plus EGFRi (Cohort 5); or BRAFi plus EGFRi naïve (Cohort 6). RAS- mutant, NF1-mutant or BRAF class 3 mutant solid tumors who have received prior SOC (Cohort 7). Exclusion Criteria: * Brain metastasis larger than 4 cm * Active malignancy within 3 years * Systemic anti-cancer therapy or small molecule therapeutics within 2 weeks prior to start of study treatment. Antibody based agents within 4 weeks prior to start of study treatment. Mitomycin C or nitrosoureas within 6 weeks prior to start of study treatment. * For participants who may get lorlatinib or encorafenib on study, history of interstitial lung disease * For participants who may get binimetinib on study, history or current evidence of retinal vein occlusion (RVO) or concurrent neuromuscular disorder associated with elevated creatine kinase (CK)

Locations (19)

Mayo Clinic in Arizona - Phoenix

Phoenix, Arizona, United States

Mayo Clinic

Outcomes

Primary Outcomes

Part 1 and Part 2- Number of participants with dose limiting toxicities (DLTs)

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

Time frame: Cycle 1 (21 days)

Part 1 and Part 2- Number of participants with treatment-emergent adverse events (AEs)

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

Time frame: Baseline up to 30 days after last dose of study medication

Part 1 and Part 2 - Number of participants with clinically significant change from baseline in laboratory abnormalities

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

Time frame: Baseline up to 30 days after last dose of study treatment

Part 1 and Part 2 - Number of dose interruptions, dose modifications, and discontinuations due to AEs

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

Time frame: Baseline up to 30 days after the last dose of study medication

Part 3- Overall response

Response will be evaluated via radiographical tumor assessments by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)

Time frame: Baseline to up to 2 years

Secondary Outcomes

Part 1 and Part 2- Maximum plasma concentration (Cmax) of PF-07284892 and metabolite

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

Data from ClinicalTrials.gov

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encorafenibDRUG

encorafenib

Scottsdale, Arizona, United States

California Cancer Associates for Research and Excellence

Encinitas, California, United States

California Cancer Associates for Research and Excellence

San Marcos, California, United States

University of Iowa

Iowa City, Iowa, United States

Brigitte Harris Cancer Pavilion

Detroit, Michigan, United States

Henry Ford Hospital

Detroit, Michigan, United States

START Midwest

Grand Rapids, Michigan, United States

Henry Ford Medical Center - Columbus

Novi, Michigan, United States

Mayo Clinic in Rochester, Minnesota

Rochester, Minnesota, United States

...and 9 more locations

Time frame: Cycle 1 Day 1 (predose, 1, 2, 4, 6, 8 hours postdose); Cycle 1 Day 18 (predose, 1, 2, 4, 6, 8, 24, and 48 hours postdose); Cycle 2-6 Day 1 (predose and 2 hours postdose); Cycle 7-12 Day 1 predose; end of treatment (EOT)

Part 1 and Part 2- Time to reach maximum plasma concentration (Tmax) of PF-07284892 and metabolite

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

Part 1 and Part 2- Area under the plasma concentration-time curve from time 0 to the last time point of quantifiable concentration (AUClast) of PF-07284892 and metabolite

Single dose PK parameter

Part 1 and Part 2- Area under the plasma concentration-time curve from time 0 to extrapolated to infinity (AUCinf) of PF-07284892 and metabolite

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

Part 1 and Part 2- Metabolite ratio of PF-07284892 and metabolite

Single dose PK parameter

Part 1 and Part 2- Area under the plasma concentration-time curve from 0 to 24 (AUC24) or 48 hours (AUC48) of PF-07284892 and metabolite

Multiple dose (assuming steady state is achieved) PK parameter

Part 1 and Part 2- Overall response

Response will be evaluated via radiographical tumor assessments by RECIST v1.1

Time frame: Baseline to up to 2 years

Part 2- Duration of Response (DOR)

Time from the first documentation of objective response to the first documentation of objective progressive disease, relapse or to death due to any cause

Time frame: Baseline to up to 2 years