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The safety and efficacy of this agent(s), or use in this setting, has not been established or is subject to confirmation. For an agent(s) whose safety and efficacy has not been established or confirmed, future regulatory approval or commercial availability is not guaranteed.
Mevrometostat (PF-06821497) is an investigational compound. Its safety and efficacy have not been established.
Active enrolling
United States, Bulgaria, China, Japan, Korea, Republic of Poland, Russian Federation, Spain
for more information at clinicaltrials.gov
EXPERIMENTAL: Dose Escalation (Part 1A)
Participants with SCLC, CRPC and FL will receive PF-06821497 at escalating dose levels
DRUG: PF-06821497
Oral continuous
EXPERIMENTAL: Dose Escalation (Part 1B)
Participants with FL will receive PF-06821497 at escalating dose levels
DRUG: PF-06821497
Oral continuous
EXPERIMENTAL: Dose Escalation (Part 1C)
Participants with CRPC will receive PF-06821497 at escalating dose levels.
DRUG: PF-06821497
Oral continuous
EXPERIMENTAL: Dose Escalation (Part 2A)
Participants with CRPC and SCLC will receive PF-06821497 at escalating dose levels in combination with SOC.
DRUG: PF-06821497
Oral continuous
EXPERIMENTAL: Dose Expansion (Part 2B)
Participants with CRPC will receive PF-06821497 in combination with SOC or SOC alone.
DRUG: PF-06821497
Oral continuous
EXPERIMENTAL: Japan Cohort
Participants with CRPC will receive PF-06821497 at one or two doses
DRUG: PF-06821497
Oral continuous
EXPERIMENTAL: China cohort
Participants will receive PF-06821497 at one or two doses
DRUG: PF-06821497
Oral continuous
EXPERIMENTAL: Dose Expansion (Part 2C)
Participants with mCRPC will receive mevrometostat at a different dose/dosing regimen than that of Part 2B in combination with SOC
DRUG: Mervometostat (PF-06821497)
Oral continuous
Histological or cytological diagnosis of advanced / metastatic solid tumor with the following tumor types in individual study parts:
Part 1A (closed to enrollment):
Part 1B (closed to enrollment):
Part 1C:
Part 2A:
• Metastatic Castration resistant prostate cancer. Patients should have received either abiraterone and/or enzalutamide treatment, may have received up to 1 line of chemotherapy and have evidence of prostate cancer progression (per PCWG3)
Part 2B/2C:
Other inclusion criteria:
-Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1.
Prior Chemotherapy: Part 1C , Japan cohort and China cohort (CRPC): no more than 2 previous regimens of chemotherapy Part 2A: mCRPC: no more than 1 previous regimen of systemic chemotherapy Part 2B (mCRPC): no more than 1 previous regimen of chemotherapy
Percentage of patients with dose limiting toxicities (DLTs) to determine the maximum tolerated dose (MTD)
First cycle DLTs will be utilized to determine the MTD
Baseline up to 90 days
Overall safety profile including adverse events
Adverse Events will be graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version \[4.03\])
Baseline up to approximately 2 years
Preliminary efficacy determination as evaluated by disease specific response criteria
Objective response using Response Evaluation Criteria in Lymphoma (RECIL) for lymphoma, Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for solid tumors including Small Cell Lung Cancer (SCLC) and Prostate Cancer Working Group 3 (PCWG3) for Castration Resistant Prostate Cancer (CRPC). Progression-free survival in Part 2B in patients with CRPC.
Through study completion, approximately 2 years past last patient first visit.
Overall safety profile including laboratory abnormalities
Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version \[4.03\]), and timing.
Baseline up to approximately 2 years
Overall safety profile including vital signs
Vital sign changes from baseline including blood pressure, heart rate, ECG changes.
Baseline up to approximately 2 years
Evaluate time to event mevrometostat and enzalutamide vs enzalutamide alone including radiographic prgression free survival
PCWG3
Baseline until disease progression or death or through study completion (approx 2 years)
Evaluate time to event anti-tumor activity of PF-06821497 including progression-free survival (PFS), PSA50, Duration of Response (DoR), Time to first skeletal related event and Time to symptomatic skeletal related event, depending on tumor type.
Time to event endpoints based on Response Evaluation Criteria in Lymphoma (RECIL) for lymphoma, Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for solid tumors including Small Cell Lung Cancer (SCLC) and Prostate Cancer Working Group 3 (PCWG3) for Castration Resistant Prostate Cancer (CRPC)
Baseline and every 21 days through time of confirmed disease progression, unacceptable toxicity, or through study completion, approximately 2 years.
Evaluate overall survival
Median time to death proportion of patients alive at 6 months, 1 year, and 2 years.
Baseline up to approximately 2 years
Pharmacokinetic Parameters: Maximum Observed Plasma Concentration (Cmax)
Single dose and multiple dose PK will be calculated as data permits
At specific timepoints from Cycle 1 day 1 to End of Treatment visit
Pharmacokinetic Parameters: Time to Reach Maximum Observed Plasma Concentration (Tmax)
Single dose and multiple dose PK will be calculated as data permits
At specific timepoints from Cycle 1 day 1 to End of Treatment visit
Pharmacokinetic Parameters: Area Under the Curve (AUC)
Single dose and multiple dose PK will be calculated as data permits
At specific timepoints from Cycle 1 day 1 to End of Treatment visit
Pharmacokinetic Parameters: Apparent Oral Clearance (CL/F)
Single dose and multiple dose PK will be calculated as data permits
At specific timepoints from Cycle 1 day 1 to End of Treatment visit
Pharmacokinetic Parameters: Apparent Volume of Distribution (Vz/F)
Single dose and multiple dose PK will be calculated as data permits
At specific timepoints from Cycle 1 day 1 to End of Treatment visit
Pharmacokinetic Parameters: Plasma Decay Half-Life (t1/2)
Singe dose and multiple dose PK will be calculated as data permits
At specific timepoints from Cycle 1 day 1 to End of Treatment visit
Evaluate the impact of PF-06821497 on patient reported outcomes.
Quality of Life and Time to Functional Status Deterioration as assessed by FACT-P.
At specific time-points from Cycle 1 Day 1 to End of Treatment visit.
Impact of mevrometostat in combination with enzalutamide, enzalutamide alone and mevrometostat alone on symptoms and symptomatic toxicity
Questionnaire customized from PRO-CTCAE.
At specific time points from Cycle1 Day 1 to end of treatment
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Sponsor: Pfizer
Collaborator: None
For more information, call or email the Pfizer Clinical Trial Contact Center:
When calling, please reference this study number: