PF-07284892 in Participants With Advanced Solid Tumors

• ClinicalTrials.gov Identifier: NCT04800822
• Recruitment Status: Active, not recruiting
• First Posted: March 16, 2021
• Last Update Posted: April 30, 2024
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: March 9, 2021
• First Posted Date: March 16, 2021
• Last Update Posted Date: April 30, 2024
• Actual Study Start Date: March 17, 2021
• Estimated Primary Completion Date: June 18, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 13, 2021)

• 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
• 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
• 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
• 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
• 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)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 13, 2021)

• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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 ANTI-TUMOR ACTIVITY OF PF-07284892 (ARRY-558) AS A SINGLE AGENT AND IN COMBINATION THERAPY IN PARTICIPANTS WITH ADVANCED SOLID TUMORS
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Solid Tumor

Intervention

• Drug: PF-07284892
  PF-07284892
  Other Name: ARRY-558
• Drug: lorlatinib
  lorlatinib
  Other Name: Lorbrena; PF-06463922, Lorviqua
• Drug: binimetinib
  binimetinib
  Other Name: Mektovi, PF-06811462, MEK162
• Biological: cetuximab
  cetuximab
  Other Name: Erbitux
• Drug: encorafenib
  encorafenib
  Other Name: Braftovi, PF-07263896, LGX818

Study Arms

• 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
  Intervention: Drug: PF-07284892
• 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
  Interventions:

  • Drug: PF-07284892
  • Drug: lorlatinib
• Experimental: Expansion Phase (Cohort 1)
  PF-07284892 + lorlatinib in participants with ALK+ NSCLC with prior lorlatinib
  Interventions:

  • Drug: PF-07284892
  • Drug: lorlatinib
• Experimental: Expansion Phase (Cohort 2)
  PF-07284892 + lorlatinib in participants with ALK+ NSCLC with no prior lorlatinib
  Interventions:

  • Drug: PF-07284892
  • Drug: lorlatinib
• Experimental: Expansion Phase (Cohort 3)
  PF-07284892 + encorafenib + cetuximab in participants with BRAF V600E mutant CRC with prior BRAF inhibitor (BRAFi) plus epidermal growth factor receptor inhibitor (EGFRi)
  Interventions:

  • Drug: PF-07284892
  • Biological: cetuximab
  • Drug: encorafenib
• Experimental: Expansion Phase (Cohort 4)
  PF-07284892 + encorafenib + cetuximab in participants with BRAF V600E mutant CRC with no prior BRAFi plus EGFRi
  Interventions:

  • Drug: PF-07284892
  • Biological: cetuximab
  • Drug: encorafenib
• Experimental: Expansion Phase (Cohort 5)
  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)
  Interventions:

  • Drug: PF-07284892
  • Drug: binimetinib
• 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
  Interventions:

  • Drug: PF-07284892
  • Biological: cetuximab
  • Drug: encorafenib
• 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
  Interventions:

  • Drug: PF-07284892
  • Drug: binimetinib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: April 1, 2024): 53
• Original Estimated Enrollment (submitted: March 13, 2021): 70
• Estimated Study Completion Date: November 29, 2025
• Estimated Primary Completion Date: June 18, 2024 (Final data collection date for primary outcome measure)

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 (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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04800822
• Other Study ID Numbers: C4481001; 2022-502431-18-00 ( Registry Identifier: CTIS (EU) ); 2022-003166-21 ( EudraCT Number ); SHP2 ( Other Identifier: Alias Study Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

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.

• Current Responsible Party: Pfizer
• Original Responsible Party: Same as current
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Pfizer
• Verification Date: April 2024