Clinical trial NCT04800822: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
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
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2021-03-16
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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)

Primary outcomes:
measure: Part 1 and Part 2- Number of participants with dose limiting toxicities (DLTs)
timeFrame: Cycle 1 (21 days)
measure: Part 1 and Part 2- Number of participants with treatment-emergent adverse events (AEs)
timeFrame: Baseline up to 30 days after last dose of study medication
measure: Part 1 and Part 2 - Number of participants with clinically significant change from baseline in laboratory abnormalities
timeFrame: Baseline up to 30 days after last dose of study treatment
measure: Part 1 and Part 2 - Number of dose interruptions, dose modifications, and discontinuations due to AEs
timeFrame: Baseline up to 30 days after the last dose of study medication
measure: Part 3- Overall response
timeFrame: Baseline to up to 2 years
Secondary outcomes:
measure: Part 1 and Part 2- Maximum plasma concentration (Cmax) of PF-07284892 and metabolite
timeFrame: 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)
measure: Part 1 and Part 2- Time to reach maximum plasma concentration (Tmax) of PF-07284892 and metabolite
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: Part 1 and Part 2- Metabolite ratio of PF-07284892 and metabolite
timeFrame: 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
measure: 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
timeFrame: 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
measure: Part 1 and Part 2- Overall response
timeFrame: Baseline to up to 2 years
measure: Part 2- Duration of Response (DOR)
timeFrame: Baseline to up to 2 years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic in Arizona - Phoenix
state: Arizona
city: Scottsdale
country: United States
facility: Mayo Clinic
state: Arizona
city: Encinitas
country: United States
facility: California Cancer Associates for Research and Excellence
state: California
city: San Marcos
country: United States
facility: California Cancer Associates for Research and Excellence
state: California
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Detroit
country: United States
facility: Brigitte Harris Cancer Pavilion
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: START Midwest
state: Michigan
city: Novi
country: United States
facility: Henry Ford Medical Center - Columbus
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic in Rochester, Minnesota
state: Minnesota
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center David H Koch Center for Cancer Care
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center Rockefeller Outpatient Pavilion
state: New York
city: Franklin
country: United States
facility: Tennessee Oncology PLLC
state: Tennessee
city: Franklin
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon Research Institute- Pharmacy
state: Tennessee
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology PLLC
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: