PF-07284892 in Participants With Advanced Solid Tumors
- Conditions
- Solid Tumor
- Interventions
- Registration Number
- NCT04800822
- Lead Sponsor
- Pfizer
- 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 available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 53
- 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).
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description PF-07284892 monotherapy PF-07284892 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 PF-07284892 in combination with encorafenib and cetuximab (Part 2) cetuximab Combination dose escalation of PF-07284892 in combination with encorafenib and cetuximab in participants with BRAF V600E mutant CRC PF-07284892 in combination with lorlatinib (Part 2) PF-07284892 Combination dose escalation of PF-07284892 in combination with lorlatinib in participants with ALK- or ROS1-positive NSCLC Expansion Phase (Cohort 1) PF-07284892 PF-07284892 + lorlatinib in participants with ALK+ NSCLC with prior lorlatinib Expansion Phase (Cohort 3) cetuximab PF-07284892 + encorafenib + cetuximab in participants with BRAF V600E mutant CRC with prior BRAF inhibitor (BRAFi) plus epidermal growth factor receptor inhibitor (EGFRi) Expansion Phase (Cohort 3) encorafenib PF-07284892 + encorafenib + cetuximab in participants with BRAF V600E mutant CRC with prior BRAF inhibitor (BRAFi) plus epidermal growth factor receptor inhibitor (EGFRi) Expansion Phase (Cohort 4) cetuximab PF-07284892 + encorafenib + cetuximab in participants with BRAF V600E mutant CRC with no prior BRAFi plus EGFRi Expansion Phase (Cohort 2) PF-07284892 PF-07284892 + lorlatinib in participants with ALK+ NSCLC with no prior lorlatinib Expansion Phase (Cohort 3) PF-07284892 PF-07284892 + encorafenib + cetuximab in participants with BRAF V600E mutant CRC with prior BRAF inhibitor (BRAFi) plus epidermal growth factor receptor inhibitor (EGFRi) PF-07284892 in combination with encorafenib and cetuximab (Part 2) PF-07284892 Combination dose escalation of PF-07284892 in combination with encorafenib and cetuximab in participants with BRAF V600E mutant CRC PF-07284892 in combination with binimetinib (Part 2) binimetinib 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 Expansion Phase (Cohort 4) PF-07284892 PF-07284892 + encorafenib + cetuximab in participants with BRAF V600E mutant CRC with no prior BRAFi plus EGFRi Expansion Phase (Cohort 5) PF-07284892 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) PF-07284892 in combination with binimetinib (Part 2) PF-07284892 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 Expansion Phase (Cohort 1) lorlatinib PF-07284892 + lorlatinib in participants with ALK+ NSCLC with prior lorlatinib PF-07284892 in combination with encorafenib and cetuximab (Part 2) encorafenib Combination dose escalation of PF-07284892 in combination with encorafenib and cetuximab in participants with BRAF V600E mutant CRC PF-07284892 in combination with lorlatinib (Part 2) lorlatinib Combination dose escalation of PF-07284892 in combination with lorlatinib in participants with ALK- or ROS1-positive NSCLC Expansion Phase (Cohort 2) lorlatinib PF-07284892 + lorlatinib in participants with ALK+ NSCLC with no prior lorlatinib Expansion Phase (Cohort 4) encorafenib PF-07284892 + encorafenib + cetuximab in participants with BRAF V600E mutant CRC with no prior BRAFi plus EGFRi Expansion Phase (Cohort 5) binimetinib 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)
- Primary Outcome Measures
Name Time Method 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
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
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
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
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
Name Time Method 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
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
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
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
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
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
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
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
Trial Locations
- Locations (16)
Brigitte Harris Cancer Pavilion
🇺🇸Detroit, Michigan, United States
Mayo Clinic in Arizona - Phoenix
🇺🇸Phoenix, Arizona, United States
Mayo Clinic
🇺🇸Scottsdale, Arizona, United States
California Cancer Associates for Research and Excellence
🇺🇸San Marcos, California, United States
University of Iowa
🇺🇸Iowa City, Iowa, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
START Midwest
🇺🇸Grand Rapids, Michigan, United States
Henry Ford Medical Center - Columbus
🇺🇸Novi, Michigan, United States
Mayo Clinic in Rochester, Minnesota
🇺🇸Rochester, Minnesota, United States
Memorial Sloan Kettering Cancer Center David H Koch Center for Cancer Care
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center Rockefeller Outpatient Pavilion
🇺🇸New York, New York, United States
Tennessee Oncology PLLC
🇺🇸Nashville, Tennessee, United States
Tennessee Oncology, PLLC
🇺🇸Nashville, Tennessee, United States
Sarah Cannon Research Institute- Pharmacy
🇺🇸Nashville, Tennessee, United States
SCRI Oncology Partners
🇺🇸Nashville, Tennessee, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States