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.
Clinical Trial Details
Geo Regions
Genitourinary Cancer
Other or Multiple Cancer Types
Mevrometostat (EZH2 Inhibitor)
Mevrometostat is an investigational compound. Its safety and efficacy have not been established.
A PHASE I DOSE ESCALATION AND EXPANDED COHORT STUDY OF PF-06821497 IN THE TREATMENT OF ADULT PATIENTS WITH RELAPSED/REFRACTORY SMALL CELL LUNG CANCER (SCLC), CASTRATION RESISTANT PROSTATE CANCER (CRPC) AND FOLLICULAR LYMPHOMA (FL)
Phase 1
NCT03460977
Active enrolling
Locations
United States, Bulgaria, China, Japan, Korea, Republic of, Poland, Russian Federation, Spain
Study design
Participant Group/Arm
EXPERIMENTAL: Dose Escalation (Part 1A)
Participants with SCLC, CRPC and FL will receive PF-06821497 at escalating dose levels
Intervention/Treatment
DRUG: PF-06821497
Oral continuous
Participant Group/Arm
EXPERIMENTAL: Dose Escalation (Part 1B)
Participants with FL will receive PF-06821497 at escalating dose levels
Intervention/Treatment
DRUG: PF-06821497
Oral continuous
Participant Group/Arm
EXPERIMENTAL: Dose Escalation (Part 1C)
Participants with CRPC will receive PF-06821497 at escalating dose levels.
Intervention/Treatment
DRUG: PF-06821497
Oral continuous
Participant Group/Arm
EXPERIMENTAL: Dose Escalation (Part 2A)
Participants with CRPC and SCLC will receive PF-06821497 at escalating dose levels in combination with SOC.
Intervention/Treatment
DRUG: PF-06821497
Oral continuous
Participant Group/Arm
EXPERIMENTAL: Dose Expansion (Part 2B)
Participants with CRPC will receive PF-06821497 in combination with SOC or SOC alone.
Intervention/Treatment
DRUG: PF-06821497
Oral continuous
Participant Group/Arm
EXPERIMENTAL: Japan Cohort
Participants with CRPC will receive PF-06821497 at one or two doses
Intervention/Treatment
DRUG: PF-06821497
Oral continuous
Participant Group/Arm
EXPERIMENTAL: China cohort
Participants will receive PF-06821497 at one or two doses
Intervention/Treatment
DRUG: PF-06821497
Oral continuous
Key eligibility criteria
Inclusion criteria
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:
- Castration resistant prostate cancer. Patients should have received either abiraterone and/or enzalutamide treatment and have evidence of prostate cancer progression (per PCWG3) Japan cohort
- Castration resistant prostate cancer that is resistant to SOC or for which no local regulatory approved SOC is available that would confer significant clinical benefit in the medical judgement of the investigator. Patients should have received either abiraterone and/or enzalutamide treatment and have evidence of prostate cancer progression (per PCWG3) China cohort
- Castration resistant prostate cancer that is intolerant/resistant to SOC or for which no local regulatory approved SOC is available that would confer significant clinical benefit in the medical judgement of the investigator. Patients who refused SOC may be eligible. Patients should have received either abiraterone and/or enzalutamide treatment and have evidence of prostate cancer progression (per PCWG3)
Part 2A:
• 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:
- Castration resistant prostate cancer. Patients should have received abiraterone treatment, may have received up to 1 prior line of chemotherapy, have not received prior enzalutamide, apalutamide or darolutamide and have evidence of prostate cancer progression (per PCWG3)
- Patients must have radiographic evidence of disease
Other inclusion criteria:
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1.
- Adequate organ function
Exclusion criteria
Prior Chemotherapy: Part 1C , Japan cohort and China cohort (CRPC): no more than 2 previous regimens of chemotherapy Part 2A: CRPC: no more than 1 previous regimen of systemic chemotherapy Part 2B (CRPC): no more than 1 previous regimen of chemotherapy
- Prior irradiation to >25% of the bone marrow.
- QTcF interval >480 msec at screening.
- Hypertension that cannot be controlled by medications (>150/90 mmHg despite optimal medical therapy).
- Known or suspected hypersensitivity to PF 06821497 or any components or enzalutamide (CRPC)
- Active inflammatory gastrointestinal disease, chronic diarrhea, known diverticular disease or previous gastric resection or lap band surgery. Gastroesophageal reflux disease under treatment with proton pump inhibitors is allowed.
- Current use or anticipated need for food or drugs that are known strong CYP3A4/5 inducers or inhibitors, including their administration within 10 days or 5 half lives of the CYP3A4/5 inhibitor, whichever is longer prior to first dose of investigational product.
Key dates
Study start date
- April 2018
Estimated primary completion date
- October 2025
Key endpoints
Primary Outcome Measures
Outcome Measure
Percentage of patients with dose limiting toxicities (DLTs) to determine the maximum tolerated dose (MTD)
Measure Description
First cycle DLTs will be utilized to determine the MTD
Time Frame
Baseline up to 90 days
Outcome Measure
Overall safety profile including adverse events
Measure Description
Adverse Events will be graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version \[4.03\])
Time Frame
Baseline up to approximately 2 years
Outcome Measure
Preliminary efficacy determination as evaluated by disease specific response criteria
Measure Description
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.
Time Frame
Through study completion, approximately 2 years past last patient first visit.
Outcome Measure
Overall safety profile including laboratory abnormalities
Measure Description
Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version \[4.03\]), and timing.
Time Frame
Baseline up to approximately 2 years
Outcome Measure
Overall safety profile including vital signs
Measure Description
Vital sign changes from baseline including blood pressure, heart rate, ECG changes.
Time Frame
Baseline up to approximately 2 years
Secondary Outcome Measures:
Outcome Measure
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.
Measure Description
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)
Time Frame
Baseline and every 21 days through time of confirmed disease progression, unacceptable toxicity, or through study completion, approximately 2 years.
Outcome Measure
Evaluate overall survival
Measure Description
Median time to death proportion of patients alive at 6 months, 1 year, and 2 years.
Time Frame
Baseline up to approximately 2 years
Outcome Measure
Pharmacokinetic Parameters: Maximum Observed Plasma Concentration (Cmax)
Measure Description
Single dose and multiple dose PK will be calculated as data permits
Time Frame
At specific timepoints from Cycle 1 day 1 to End of Treatment visit
Outcome Measure
Pharmacokinetic Parameters: Time to Reach Maximum Observed Plasma Concentration (Tmax)
Measure Description
Single dose and multiple dose PK will be calculated as data permits
Time Frame
At specific timepoints from Cycle 1 day 1 to End of Treatment visit
Outcome Measure
Pharmacokinetic Parameters: Area Under the Curve (AUC)
Measure Description
Single dose and multiple dose PK will be calculated as data permits
Time Frame
At specific timepoints from Cycle 1 day 1 to End of Treatment visit
Outcome Measure
Pharmacokinetic Parameters: Apparent Oral Clearance (CL/F)
Measure Description
Single dose and multiple dose PK will be calculated as data permits
Time Frame
At specific timepoints from Cycle 1 day 1 to End of Treatment visit
Outcome Measure
Pharmacokinetic Parameters: Apparent Volume of Distribution (Vz/F)
Measure Description
Single dose and multiple dose PK will be calculated as data permits
Time Frame
At specific timepoints from Cycle 1 day 1 to End of Treatment visit
Outcome Measure
Pharmacokinetic Parameters: Plasma Decay Half-Life (t1/2)
Measure Description
Singe dose and multiple dose PK will be calculated as data permits
Time Frame
At specific timepoints from Cycle 1 day 1 to End of Treatment visit
Outcome Measure
Evaluate the impact of PF-06821497 on patient reported outcomes.
Measure Description
Quality of Life and Time to Functional Status Deterioration as assessed by FACT-P.
Time Frame
At specific time-points from Cycle 1 Day 1 to End of Treatment visit.
Number of participants
267
Collaborators and investigators
Sponsor: Pfizer
Collaborator: None