PF-07284892 in Participants With Advanced Solid Tumors

NCT04800822 | Terminated Phase 1 FDA Drug

• 4 other identifiers: C44810012022-502431-18-002022-003166-21SHP2
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 19

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.

Conditions

Solid Tumor

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

Outcome Measures

Primary Outcomes (5)

• 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

  Cycle 1 (21 days)

• 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

  Baseline up to 30 days after last dose of study medication

• 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

  Baseline up to 30 days after last dose of study treatment

• 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

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

• 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)

  Baseline to up to 2 years

Secondary Outcomes (8)

• 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)

• 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

• 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

• 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

• 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

Study Arms (9)

PF-07284892 monotherapy

EXPERIMENTAL

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 in combination with lorlatinib (Part 2)

EXPERIMENTAL

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

Drug: PF-07284892; Drug: lorlatinib

Expansion Phase (Cohort 1)

EXPERIMENTAL

PF-07284892 + lorlatinib in participants with ALK+ NSCLC with prior lorlatinib

Drug: PF-07284892; Drug: lorlatinib

Expansion Phase (Cohort 2)

EXPERIMENTAL

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

Drug: PF-07284892; Drug: lorlatinib

Expansion Phase (Cohort 3)

EXPERIMENTAL

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

Drug: PF-07284892; Biological: cetuximab; Drug: encorafenib

Expansion Phase (Cohort 4)

EXPERIMENTAL

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

Drug: PF-07284892; Biological: cetuximab; Drug: encorafenib

Expansion Phase (Cohort 5)

EXPERIMENTAL

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; Drug: binimetinib

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

EXPERIMENTAL

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

Drug: PF-07284892; Biological: cetuximab; Drug: encorafenib

PF-07284892 in combination with binimetinib (Part 2)

EXPERIMENTAL

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; Drug: binimetinib

Interventions

PF-07284892 DRUG

PF-07284892

Also known as: ARRY-558

Expansion Phase (Cohort 1); Expansion Phase (Cohort 2); Expansion Phase (Cohort 3); Expansion Phase (Cohort 4); Expansion Phase (Cohort 5); PF-07284892 in combination with binimetinib (Part 2); PF-07284892 in combination with encorafenib and cetuximab (Part 2); PF-07284892 in combination with lorlatinib (Part 2); PF-07284892 monotherapy

lorlatinib DRUG

lorlatinib

Also known as: Lorbrena; PF-06463922, Lorviqua

Expansion Phase (Cohort 1); Expansion Phase (Cohort 2); PF-07284892 in combination with lorlatinib (Part 2)

binimetinib DRUG

binimetinib

Also known as: Mektovi, PF-06811462, MEK162

Expansion Phase (Cohort 5); PF-07284892 in combination with binimetinib (Part 2)

cetuximab BIOLOGICAL

cetuximab

Also known as: Erbitux

Expansion Phase (Cohort 3); Expansion Phase (Cohort 4); PF-07284892 in combination with encorafenib and cetuximab (Part 2)

encorafenib DRUG

encorafenib

Also known as: Braftovi, PF-07263896, LGX818

Expansion Phase (Cohort 3); Expansion Phase (Cohort 4); PF-07284892 in combination with encorafenib and cetuximab (Part 2)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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)

Sponsors & Collaborators

• Pfizer: lead

Study Sites (19)

Mayo Clinic in Arizona - Phoenix

Phoenix, Arizona, 85054, United States

Location

Mayo Clinic

Scottsdale, Arizona, 85259, United States

Location

California Cancer Associates for Research and Excellence

Encinitas, California, 92024, United States

Location

California Cancer Associates for Research and Excellence

San Marcos, California, 92069, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Brigitte Harris Cancer Pavilion

Detroit, Michigan, 48202, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

START Midwest

Grand Rapids, Michigan, 49546, United States

Location

Henry Ford Medical Center - Columbus

Novi, Michigan, 48377, United States

Location

Mayo Clinic in Rochester, Minnesota

Rochester, Minnesota, 55905, United States

Location

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

New York, New York, 10021, United States

Location

Memorial Sloan Kettering Cancer Center Rockefeller Outpatient Pavilion

New York, New York, 10022, United States

Location

Tennessee Oncology PLLC

Franklin, Tennessee, 37067, United States

Location

Tennessee Oncology, PLLC

Franklin, Tennessee, 37067, United States

Location

Sarah Cannon Research Institute- Pharmacy

Nashville, Tennessee, 37203, United States

Location

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

Location

Tennessee Oncology PLLC

Nashville, Tennessee, 37203, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37203, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Colorectal Neoplasms; Carcinoma, Non-Small-Cell Lung; Hereditary Sensory and Autonomic Neuropathies; Neurofibromatosis 1

Interventions

lorlatinib; binimetinib; Cetuximab; encorafenib

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Neurofibromatoses; Neurofibroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Neoplasms by Histologic Type; Neoplastic Syndromes, Hereditary; Neurocutaneous Syndromes

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2021
• First Posted: March 16, 2021
• Study Start: March 17, 2021
• Primary Completion: June 19, 2024
• Study Completion: June 19, 2024
• Last Updated: October 22, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (19)