Solid Tumor
Conditions
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
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.
Interventions
DRUGPF-07284892
PF-07284892
DRUGlorlatinib
lorlatinib
DRUGbinimetinib
binimetinib
BIOLOGICALcetuximab
cetuximab
DRUGencorafenib
encorafenib
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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 (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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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
| Measure | Time frame | Description |
|---|---|---|
| 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- 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 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- 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 |
Countries
United States
Contacts
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Outcome results
None listed