Clinical Trials /

PF-07284892 in Participants With Advanced Solid Tumors

NCT04800822

Description:

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.

Related Conditions:
  • Colorectal Carcinoma
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: PF-07284892 in Participants With Advanced Solid Tumors
  • 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 Antitumor Activity of PF-07284892 (ARRY-558) as a Single Agent and in Combination Therapy in Participants With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: C4481001
  • NCT ID: NCT04800822

Conditions

  • Solid Tumor

Interventions

DrugSynonymsArms
PF-07284892ARRY-558Expansion Phase (Cohort 1)
lorlatinibLorbrena; PF-06463922, LorviquaExpansion Phase (Cohort 1)
binimetinibMektovi, PF-06811462, MEK162Expansion Phase (Cohort 7)
cetuximabErbituxExpansion Phase (Cohort 4)
encorafenibBraftovi, PF-07263896Expansion Phase (Cohort 4)

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
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
  • 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
  • PF-07284892
  • lorlatinib
  • binimetinib
  • cetuximab
  • encorafenib
Expansion Phase (Cohort 1)ExperimentalPF-07284892 + lorlatinib in participants with ALK+ NSCLC with prior lorlatinib without prior platinum-based chemotherapy
  • PF-07284892
  • lorlatinib
Expansion Phase (Cohort 2)ExperimentalPF-07284892 + lorlatinib in participants with ALK+ NSCLC with prior lorlatinib with prior platinum-based chemotherapy
  • PF-07284892
  • lorlatinib
Expansion Phase (Cohort 3)ExperimentalPF-07284892 + lorlatinib in participants with ALK+ NSCLC with no prior lorlatinib
  • PF-07284892
  • lorlatinib
Expansion Phase (Cohort 4)ExperimentalPF-07284892 + encorafenib + cetuximab in participants with BRAF V600E mutant CRC resistant to BRAF inhibitor (BRAFi) plus epidermal growth factor receptor inhibitor (EGFRi)
  • PF-07284892
  • cetuximab
  • encorafenib
Expansion Phase (Cohort 5)ExperimentalPF-07284892 + encorafenib + cetuximab in participants with BRAF V600E mutant CRC refractory to BRAFi plus EGFRi
  • PF-07284892
  • cetuximab
  • encorafenib
Expansion Phase (Cohort 6)ExperimentalPF-07284892 + encorafenib + cetuximab in participants with BRAF V600E mutant CRC with no prior BRAFi plus EGFRi
  • PF-07284892
  • cetuximab
  • encorafenib
Expansion Phase (Cohort 7)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)
  • PF-07284892
  • 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
  • PF-07284892
  • cetuximab
  • 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
  • PF-07284892
  • binimetinib

Eligibility Criteria

        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

          -  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)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part 1 and Part 2- Number of participants with dose limiting toxicities (DLTs)
Time Frame:Cycle 1 (21 days)
Safety Issue:
Description: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

Secondary Outcome Measures

Measure:Part 1 and Part 2- Maximum plasma concentration (Cmax) of PF-07284892 and metabolite
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)
Safety Issue:
Description:single dose (Cmax) and multiple dose (assuming steady state is achieved; Css,max) pharmacokinetic (PK) parameters
Measure:Part 1 and Part 2- Time to reach maximum plasma concentration (Tmax) of PF-07284892 and metabolite
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; EOT
Safety Issue:
Description:Single dose (Tmax) and multiple dose (assuming steady state is achieved; Tss,max) pharmacokinetic parameters
Measure: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
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; EOT
Safety Issue:
Description:Single dose PK parameter
Measure: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
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; EOT
Safety Issue:
Description:Single dose and multiple dose (assuming steady state is achieved) PK parameter
Measure:Part 1 and Part 2- Metabolite ratio of PF-07284892 and metabolite
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; EOT
Safety Issue:
Description:Single dose PK parameter
Measure: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
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; EOT
Safety Issue:
Description:Multiple dose (assuming steady state is achieved) PK parameter
Measure:Part 1 and Part 2- Overall response
Time Frame:Baseline to up to 2 years
Safety Issue:
Description:Response will be evaluated via radiographical tumor assessments by RECIST v1.1
Measure:Part 2- Duration of Response (DOR)
Time Frame:Baseline to up to 2 years
Safety Issue:
Description:Time from the first documentation of objective response to the first documentation of objective progressive disease, relapse or to death due to any cause

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Pfizer

Trial 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

Last Updated

March 16, 2021