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

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Molecule overview Clinical trials

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

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Study design Key eligibility criteria Key dates Key endpoints Number of participants Collaborators and investigators

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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

Participant Group/Arm

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

Intervention/Treatment

DRUG: Mervometostat (PF-06821497)

Oral continuous

Study design table for Clinical Trial

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:

Metastatic 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:

• 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:

Metastatic 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.

Exclusion criteria

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

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

December 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

Outcome Measure

Evaluate time to event mevrometostat and enzalutamide vs enzalutamide alone including radiographic prgression free survival

Measure Description

PCWG3

Time Frame

Baseline until disease progression or death or through study completion (approx 2 years)

Primary Outcome Measures table for Clinical Trial

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)