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AzTrials

Solid TumorPhase 1NCT04800822

PF-07284892 in Participants With Advanced Solid Tumors

A Phase 1 study testing PF-07284892, lorlatinib and binimetinib in people with Solid Tumor, run by Pfizer at 11 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Solid Tumor
What is being tested?
PF-07284892, lorlatinib and binimetinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
53 participants
Where
11 sitesUnited States
Study dates
17 Mar 2021to 19 Jun 2024
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).

Who cannot join

  • 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)

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

United States11 sites

  • Brigitte Harris Cancer Pavilion

    Detroit, Michigan, 48202

  • Henry Ford Hospital

    Detroit, Michigan, 48202

  • Tennessee Oncology PLLC

    Franklin, Tennessee, 37067

  • START Midwest

    Grand Rapids, Michigan, 49546

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • SCRI Oncology Partners

    Nashville, Tennessee, 37203

  • Memorial Sloan Kettering Cancer Center David H Koch Center for Cancer Care

    New York, New York, 10021

  • Memorial Sloan Kettering Cancer Center Rockefeller Outpatient Pavilion

    New York, New York, 10022

  • Henry Ford Medical Center - Columbus

    Novi, Michigan, 48377

  • Mayo Clinic in Arizona - Phoenix

    Phoenix, Arizona, 85054

  • Mayo Clinic

    Scottsdale, Arizona, 85259

Other trials in United States

About this study

Official title: A PHASE 1, OPEN-LABEL, MULTI-CENTER, DOSE ESCALATION AND DOSE EXPANSION STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND PRELIMINARY EVIDENCE OF ANTI-TUMOR ACTIVITY OF PF-07284892 (ARRY-558) AS A SINGLE AGENT AND IN COMBINATION THERAPY IN PARTICIPANTS WITH ADVANCED SOLID TUMORS

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.

Conditions
Solid Tumor
Being tested
PF-07284892, lorlatinib, binimetinib, cetuximab, encorafenib
Keywords
colorectal cancer, non-small cell lung cancer, B-type Raf proto-oncogene (BRAF) mutation, Ras mutation, anaplastic lymphoma kinase (ALK)-positive, neurofibromatosis type 1 (NF1), ROS1
Medical subject headings
Colorectal Neoplasms, Carcinoma, Non-Small-Cell Lung, Hereditary Sensory and Autonomic Neuropathies, Neurofibromatosis 1

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PF-07284892Drug

    Also called ARRY-558

    PF-07284892

  • lorlatinibDrug

    Also called Lorbrena; PF-06463922, Lorviqua

    lorlatinib

  • binimetinibDrug

    Also called Mektovi, PF-06811462, MEK162

    binimetinib

  • cetuximabBiological

    Also called Erbitux

    cetuximab

  • encorafenibDrug

    Also called Braftovi, PF-07263896, LGX818

    encorafenib

Study groups in NCT04800822
Study groupRoleWhat they receive
PF-07284892 monotherapyExperimentalMonotherapy dose escalation of PF-07284892 in participants with ALK- or ROS1-positive non-small cell lung cancer (NSCLC), B-type Raf proto-oncogene V600E mutation colorectal cancer (CRC), or RAS- mutant, NF1-mutant or BRAF class 3-mutant solid tumors
Receives: Drug: PF-07284892
PF-07284892 in combination with lorlatinib (Part 2)ExperimentalCombination dose escalation of PF-07284892 in combination with lorlatinib in participants with ALK- or ROS1-positive NSCLC
Receives: Drug: PF-07284892; Drug: lorlatinib
Expansion Phase (Cohort 1)ExperimentalPF-07284892 + lorlatinib in participants with ALK+ NSCLC with prior lorlatinib
Receives: Drug: PF-07284892; Drug: lorlatinib
Expansion Phase (Cohort 2)ExperimentalPF-07284892 + lorlatinib in participants with ALK+ NSCLC with no prior lorlatinib
Receives: Drug: PF-07284892; Drug: lorlatinib
Expansion Phase (Cohort 3)ExperimentalPF-07284892 + encorafenib + cetuximab in participants with BRAF V600E mutant CRC with prior BRAF inhibitor (BRAFi) plus epidermal growth factor receptor inhibitor (EGFRi)
Receives: Drug: PF-07284892; Biological: cetuximab; Drug: encorafenib
Expansion Phase (Cohort 4)ExperimentalPF-07284892 + encorafenib + cetuximab in participants with BRAF V600E mutant CRC with no prior BRAFi plus EGFRi
Receives: Drug: PF-07284892; Biological: cetuximab; Drug: encorafenib
Expansion Phase (Cohort 5)ExperimentalPF-07284892 + binimetinib in participants with RAS- mutant, NF1-mutant or BRAF class 3 mutant solid tumors who have received prior standard of care (SOC)
Receives: Drug: PF-07284892; Drug: binimetinib
PF-07284892 in combination with encorafenib and cetuximab (Part 2)ExperimentalCombination dose escalation of PF-07284892 in combination with encorafenib and cetuximab in participants with BRAF V600E mutant CRC
Receives: Drug: PF-07284892; Biological: cetuximab; Drug: encorafenib
PF-07284892 in combination with binimetinib (Part 2)ExperimentalCombination dose escalation of PF-07284892 in combination with binimetinib in participants with Ras-mutant, NF-1 mutant or BRAF class 3 -mutant solid tumors
Receives: Drug: PF-07284892; Drug: binimetinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: Cycle 1 (21 days)

  2. 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

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

  3. 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

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

  4. 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

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

  5. 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)

    Measured: Baseline to up to 2 years

Secondary outcomes (8)

  1. 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

    Measured: 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)

  2. 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

    Measured: 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; EOT

  3. 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

    Measured: 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; EOT

  4. 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

    Measured: 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; EOT

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

    Single dose PK parameter

    Measured: 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; EOT

  6. 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

    Measured: 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; EOT

  7. Part 1 and Part 2- Overall response

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

    Measured: Baseline to up to 2 years

  8. 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

    Measured: Baseline to up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Mar 2021
  2. Study start17 Mar 2021
  3. Primary completion19 Jun 2024
  4. Study completion19 Jun 2024

Why it stopped: The study was prematurely discontinued due to strategic reasons. The PF-07284892 program will continue

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
53 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04800822
Sponsor's protocol ID
C4481001
Other IDs
SHP2, 2022-502431-18-00
Status last verified
May 2025
First submitted
9 Mar 2021
Last updated
4 Jun 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: 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.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing PF-07284892, lorlatinib and binimetinib in people with Solid Tumor, run by Pfizer at 11 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 4 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: The study was prematurely discontinued due to strategic reasons. The PF-07284892 program will continue). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1 and Part 2- Number of participants with dose limiting toxicities (DLTs) (time frame: Cycle 1 (21 days)). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04800822.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2026.

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