PF-07284892 in Participants With Advanced Solid Tumors

Solid Tumor Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04800822
• Other study ID #: C4481001
• Secondary ID: 2022-502431-18-0
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: March 17, 2021
• Est. completion date: November 29, 2025

Study information

• Verified date: April 2024
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 53
• Est. completion date: November 29, 2025
• Est. primary completion date: June 18, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumor

Intervention

Drug:
• PF-07284892
PF-07284892
• lorlatinib
lorlatinib
• binimetinib
binimetinib

Biological:
• cetuximab
cetuximab

Drug:
• encorafenib
encorafenib

Locations

Country	Name	City	State
United States	Henry Ford Hospital	Detroit	Michigan
United States	California Cancer Associates for Research and Excellence	Encinitas	California
United States	Tennessee Oncology PLLC	Franklin	Tennessee
United States	Tennessee Oncology, PLLC	Franklin	Tennessee
United States	START Midwest	Grand Rapids	Michigan
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	University of Iowa	Iowa City	Iowa
United States	Sarah Cannon Research Institute- Pharmacy	Nashville	Tennessee
United States	SCRI Oncology Partners	Nashville	Tennessee
United States	Tennessee Oncology PLLC	Nashville	Tennessee
United States	Tennessee Oncology, PLLC	Nashville	Tennessee
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	Henry Ford Medical Center - Columbus	Novi	Michigan
United States	Mayo Clinic in Arizona - Phoenix	Phoenix	Arizona
United States	Mayo Clinic in Rochester, Minnesota	Rochester	Minnesota
United States	California Cancer Associates for Research and Excellence	San Marcos	California
United States	Mayo Clinic	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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
Primary	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
Primary	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
Primary	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	Part 1 and Part 2- Maximum plasma concentration (Cmax) of PF-07284892 and metabolite	single dose (Cmax) and multiple dose (assuming steady state is achieved; Css,max) pharmacokinetic (PK) parameters	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)
Secondary	Part 1 and Part 2- Time to reach maximum plasma concentration (Tmax) of PF-07284892 and metabolite	Single dose (Tmax) and multiple dose (assuming steady state is achieved; Tss,max) pharmacokinetic parameters	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
Secondary	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	Single dose PK parameter	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
Secondary	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	Single dose and multiple dose (assuming steady state is achieved) PK parameter	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
Secondary	Part 1 and Part 2- Metabolite ratio of PF-07284892 and metabolite	Single dose PK parameter	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
Secondary	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	Multiple dose (assuming steady state is achieved) PK parameter	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
Secondary	Part 1 and Part 2- Overall response	Response will be evaluated via radiographical tumor assessments by RECIST v1.1	Baseline to up to 2 years
Secondary	Part 2- Duration of Response (DOR)	Time from the first documentation of objective response to the first documentation of objective progressive disease, relapse or to death due to any cause	Baseline to up to 2 years

External Links

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