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PF-07284892 in Participants With Advanced Solid Tumors

Sponsor
Pfizer (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04800822
Collaborator
(none)
211
Enrollment
7
Locations
11
Arms
70.6
Anticipated Duration (Months)
30.1
Patients Per Site
0.4
Patients Per Site Per Month

Study Details

Study Description

Brief 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 activity of single agent and each combination therapy.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Anticipated Enrollment :
211 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Mar 17, 2021
Anticipated Primary Completion Date :
Feb 4, 2026
Anticipated Study Completion Date :
Feb 4, 2027

Arms and Interventions

Arm Intervention/Treatment
Experimental: PF-07284892 monotherapy

Monotherapy 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

Drug: PF-07284892
PF-07284892
Other Names:
  • ARRY-558

    		•
    Experimental: PF-07284892 in combination with lorlatinib (Part 2)

    Combination dose escalation of PF-07284892 in combination with lorlatinib in participants with ALK- or ROS1-positive NSCLC

    Drug: PF-07284892
    PF-07284892
    Other Names:
  • ARRY-558

    • Drug: lorlatinib
    lorlatinib
    Other Names:
  • Lorbrena; PF-06463922, Lorviqua

    		•
    Experimental: Expansion Phase (Cohort 1)

    PF-07284892 + lorlatinib in participants with ALK+ NSCLC with prior lorlatinib without prior platinum-based chemotherapy

    Drug: PF-07284892
    PF-07284892
    Other Names:
  • ARRY-558

    • Drug: lorlatinib
    lorlatinib
    Other Names:
  • Lorbrena; PF-06463922, Lorviqua

    		•
    Experimental: Expansion Phase (Cohort 2)

    PF-07284892 + lorlatinib in participants with ALK+ NSCLC with prior lorlatinib with prior platinum-based chemotherapy

    Drug: PF-07284892
    PF-07284892
    Other Names:
  • ARRY-558

    • Drug: lorlatinib
    lorlatinib
    Other Names:
  • Lorbrena; PF-06463922, Lorviqua

    		•
    Experimental: Expansion Phase (Cohort 3)

    PF-07284892 + lorlatinib in participants with ALK+ NSCLC with no prior lorlatinib

    Drug: PF-07284892
    PF-07284892
    Other Names:
  • ARRY-558

    • Drug: lorlatinib
    lorlatinib
    Other Names:
  • Lorbrena; PF-06463922, Lorviqua

    		•
    Experimental: Expansion Phase (Cohort 4)

    PF-07284892 + encorafenib + cetuximab in participants with BRAF V600E mutant CRC resistant to BRAF inhibitor (BRAFi) plus epidermal growth factor receptor inhibitor (EGFRi)

    Drug: PF-07284892
    PF-07284892
    Other Names:
  • ARRY-558

    • Biological: cetuximab
    cetuximab
    Other Names:
  • Erbitux

    • Drug: encorafenib
    encorafenib
    Other Names:
  • Braftovi, PF-07263896, LGX818

    		•
    Experimental: Expansion Phase (Cohort 5)

    PF-07284892 + encorafenib + cetuximab in participants with BRAF V600E mutant CRC refractory to BRAFi plus EGFRi

    Drug: PF-07284892
    PF-07284892
    Other Names:
  • ARRY-558

    • Biological: cetuximab
    cetuximab
    Other Names:
  • Erbitux

    • Drug: encorafenib
    encorafenib
    Other Names:
  • Braftovi, PF-07263896, LGX818

    		•
    Experimental: Expansion Phase (Cohort 6)

    PF-07284892 + encorafenib + cetuximab in participants with BRAF V600E mutant CRC with no prior BRAFi plus EGFRi

    Drug: PF-07284892
    PF-07284892
    Other Names:
  • ARRY-558

    • Biological: cetuximab
    cetuximab
    Other Names:
  • Erbitux

    • Drug: encorafenib
    encorafenib
    Other Names:
  • Braftovi, PF-07263896, LGX818

    		•
    Experimental: Expansion Phase (Cohort 7)

    PF-07284892 + binimetinib in participants with RAS- mutant, NF1-mutant or BRAF class 3 mutant solid tumors who have received prior standard of care (SOC)

    Drug: PF-07284892
    PF-07284892
    Other Names:
  • ARRY-558

    • Drug: binimetinib
    binimetinib
    Other Names:
  • Mektovi, PF-06811462, MEK162

    		•
    Experimental: PF-07284892 in combination with encorafenib and cetuximab (Part 2)

    Combination dose escalation of PF-07284892 in combination with encorafenib and cetuximab in participants with BRAF V600E mutant CRC

    Drug: PF-07284892
    PF-07284892
    Other Names:
  • ARRY-558

    • Biological: cetuximab
    cetuximab
    Other Names:
  • Erbitux

    • Drug: encorafenib
    encorafenib
    Other Names:
  • Braftovi, PF-07263896, LGX818

    		•
    Experimental: PF-07284892 in combination with binimetinib (Part 2)

    Combination dose escalation of PF-07284892 in combination with binimetinib in participants with Ras-mutant, NF-1 mutant or BRAF class 3 -mutant solid tumors

    Drug: PF-07284892
    PF-07284892
    Other Names:
  • ARRY-558

    • Drug: binimetinib
    binimetinib
    Other Names:
  • Mektovi, PF-06811462, MEK162

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Part 1 and Part 2- Number of participants with dose limiting toxicities (DLTs) [Cycle 1 (21 days)]

      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

    2. Part 1 and Part 2- Number of participants with treatment-emergent adverse events (AEs) [Baseline up to 30 days after last dose of study medication]

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

    3. Part 1 and Part 2 - Number of participants with clinically significant change from baseline in laboratory abnormalities [Baseline up to 30 days after last dose of study treatment]

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

    4. Part 1 and Part 2 - Number of dose interruptions, dose modifications, and discontinuations due to AEs [Baseline up to 30 days after the last dose of study medication]

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

    5. Part 3- Overall response [Baseline to up to 2 years]

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

    Secondary Outcome Measures

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

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

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

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

    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 [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]

      Single dose PK parameter

    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 [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]

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

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

      Single dose PK parameter

    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 [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]

      Multiple dose (assuming steady state is achieved) PK parameter

    7. Part 1 and Part 2- Overall response [Baseline to up to 2 years]

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

    8. Part 2- Duration of Response (DOR) [Baseline to up to 2 years]

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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 UC Irvine Health Orange California United States 92868
    2 START Midwest Grand Rapids Michigan United States 49546
    3 Memorial Sloan Kettering Cancer Center David H Koch Center for Cancer Care New York New York United States 10021
    4 Memorial Sloan Kettering Cancer Center Rockefeller Outpatient Pavilion New York New York United States 10022
    5 Tennessee Oncology, PLLC Franklin Tennessee United States 37067
    6 Tennessee Oncology PLLC Nashville Tennessee United States 37203
    7 The University of Texas MD Anderson Cancer Center Houston Texas United States 77030

    Sponsors and Collaborators

    • Pfizer

    Investigators

    • Study Director: Pfizer CT.gov Call Center, Pfizer

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Pfizer
    ClinicalTrials.gov Identifier:
    NCT04800822
    Other Study ID Numbers:
    • C4481001
    First Posted:
    Mar 16, 2021
    Last Update Posted:
    Mar 3, 2022
    Last Verified:
    Feb 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Pfizer
    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
    Additional relevant MeSH terms:
    Neoplasms
    Cetuximab

    Study Results

    No Results Posted as of Mar 3, 2022