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
DRUGencorafenib
encorafenib
DRUGPF-07284892
PF-07284892
DRUGlorlatinib
lorlatinib
DRUGbinimetinib
binimetinib
BIOLOGICALcetuximab
cetuximab
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- 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- 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 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 |
| 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 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 |
Countries
United States
Outcome results
None listed