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PF-07284892 in Participants With Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT04800822
Recruitment Status : Recruiting
First Posted : March 16, 2021
Last Update Posted : July 30, 2021
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Description
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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
Solid Tumor Drug: PF-07284892 Drug: lorlatinib Drug: binimetinib Biological: cetuximab Drug: encorafenib Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated 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 Antitumor Activity of PF-07284892 (ARRY-558) as a Single Agent and in Combination Therapy in Participants With Advanced Solid Tumors
Actual Study Start Date : March 17, 2021
Estimated Primary Completion Date : February 4, 2026
Estimated Study Completion Date : February 4, 2027

Resource links provided by the National Library of Medicine


Arms and Interventions
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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 Name: 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 Name: ARRY-558

Drug: lorlatinib
lorlatinib
Other Name: 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 Name: ARRY-558

Drug: lorlatinib
lorlatinib
Other Name: 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 Name: ARRY-558

Drug: lorlatinib
lorlatinib
Other Name: 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 Name: ARRY-558

Drug: lorlatinib
lorlatinib
Other Name: 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 Name: ARRY-558

Biological: cetuximab
cetuximab
Other Name: Erbitux

Drug: encorafenib
encorafenib
Other Name: 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 Name: ARRY-558

Biological: cetuximab
cetuximab
Other Name: Erbitux

Drug: encorafenib
encorafenib
Other Name: 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 Name: ARRY-558

Biological: cetuximab
cetuximab
Other Name: Erbitux

Drug: encorafenib
encorafenib
Other Name: 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 Name: ARRY-558

Drug: binimetinib
binimetinib
Other Name: 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 Name: ARRY-558

Biological: cetuximab
cetuximab
Other Name: Erbitux

Drug: encorafenib
encorafenib
Other Name: 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 Name: ARRY-558

Drug: binimetinib
binimetinib
Other Name: Mektovi, PF-06811462, MEK162


Outcome Measures
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Primary Outcome Measures :
  1. Part 1 and Part 2- Number of participants with dose limiting toxicities (DLTs) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ 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) ]
    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 [ 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 ]
    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 [ 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 ]
    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 [ 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 ]
    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 [ 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 ]
    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 [ 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 ]
    Multiple dose (assuming steady state is achieved) PK parameter

  7. Part 1 and Part 2- Overall response [ Time Frame: 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) [ Time Frame: 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
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04800822


Contacts
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Contact: Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com

Locations
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United States, California
UC Irvine Health Recruiting
Orange, California, United States, 92868
United States, Michigan
START Midwest Recruiting
Grand Rapids, Michigan, United States, 49546
United States, New York
Memorial Sloan Kettering Cancer Center David H Koch Center for Cancer Care Recruiting
New York, New York, United States, 10021
Memorial Sloan Kettering Cancer Center Rockefeller Outpatient Pavilion Recruiting
New York, New York, United States, 10022
United States, Tennessee
Tennessee Oncology, PLLC Recruiting
Franklin, Tennessee, United States, 37067
Sarah Cannon Research Institute (Pharmacy) Recruiting
Nashville, Tennessee, United States, 37203
Tennessee Oncology PLLC Recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
The University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
More Information
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Additional Information:

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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT04800822    
Other Study ID Numbers: C4481001
First Posted: March 16, 2021    Key Record Dates
Last Update Posted: July 30, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: 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.

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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:
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Neoplasms
Cetuximab
Antineoplastic Agents, Immunological
Antineoplastic Agents