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NCT Number: NCT03460977

A Study of Mevrometostat for Treatment of Relapsed/Refractory SCLC, Castration Resistant Prostate Cancer, and Follicular Lymphoma

The purpose of this study is to learn about the safety and effects of the study medicine (called Mevrometostat) for the possible treatment of Relapsed/ Refractory Small Cell Lung Cancer (SCLC), Castration Resistant Prostate Cancer (CRPC) and Follicular Lymphoma (FL). The study consists of 3 parts; Part 1 and 2 enrolled participants with SCLC, metastatic CRPC, and FL are closed for enrollment.

Part 3, which is open for enrollment is seeking men who:

* have Castration Resistant Prostate Cancer (CRPC) and * have previously received treatment for CRPC and have progressed from the last treatment

All participants in Part 3 of this study will receive mevrometostat and/ or enzalutamide. Part 3 consists of 2 sub studies each has an assessment phase and a maintenance phase. The Part 3 DDI substudy consist of 2 cohorts, Cohort 1 (monotherapy cohort) and Cohort 2 (Combination cohort).

In the assessment phase:

* participants in the BE substudy will take 3 single doses of mevrometostat by mouth over 3 periods. * participants in the DDI substudy Cohort 1 (monotherapy cohort) will take mevrometostat 2 times a day and/or itraconazole 1 time a day based on a present schedule. * participants in the DDI substudy Cohort 2 (combination cohort) will take mevrometostat 2 times a day, enzalutamide 1 time a day, and/or itraconazole 1 time a day based on a present schedule.

After completion of the assessment phase, participants will enter the maintenance phase where they will receive mevrometostat 2 times a day and enzalutamide 1 time a day by mouth until their cancer is no longer responding.

The study will look at the experiences of participanrs receiving the study medicine. This will help see if the study medicine is safe and effective.

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Key information

Conditions

Metastatic Castration Resistant Prostate Cancer (mCRPC) Bronchial Neoplasms Carcinoma, Bronchogenic Disease Attributes Follicular Lymphoma (FL) Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Lung Diseases Lung Neoplasms Lymphatic Diseases Lymphoma Lymphoma, Follicular Lymphoma, Non-Hodgkin Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type Neoplasms by Site Pathologic Processes Pathological Conditions, Signs and Symptoms Recurrence Respiratory Tract Diseases Respiratory Tract Neoplasms Small Cell Lung Cancer (SCLC) Small Cell Lung Carcinoma Thoracic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Specialized Hospital for Active Treatment of Oncology - Haskovo, Haskovo, Bulgaria

Loading trial locations.

About this study

This is an open label, multi center, Phase 1 dose escalation and dose expansion study of mevrometostat (PF-06821497) administered orally BID as a single agent or in combination with SOC to patients with CRPC, SCLC, and FL. The study consists of three parts (Part 1, Part 2, and Part 3) along with the Japan and China monotherapy cohorts. Part 1 and Part 2 are closed for enrollment. Part 1 tested monotherapy in 3 cohorts (Parts 1A, 1B, and 1C); Part 2 tested combination therapy in Parts 2A (dose escalation), 2B and 2C (does expansion).

Part 3 consists of the Bioequivalence (BE) and drug-drug interaction (DDI) substudies and are open for enrollment. The BE substudy will test between 2 mevrometostat formulation to confirm that they work in the body the same way. The DDI substudy will evaluate the effect of a strong CYP3A4 (an enzyme in your body that breaks down/ removes drugs) inhibitor on the PK of mevrometostat; a strong CYP3A4 inhibitor may slow down the breakdown/ removal of drugs in your body. The Sponsor may choose to delay or discontinue any cohorts or substudies.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Part 1 and Part 2 (Closed for enrollment).

Part 3 Key Inclusion Criteria:

  • Histological or cytological diagnosis of castration resistant prostate cancer.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0-2 with expected life expectancy of at least 6 months.
  • Adequate bone marrow, renal, and liver function

Part 3 Key Exclusion Criteria:

  • 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.
  • Current use or anticipated need for food or drugs that are known strong and moderate CYP3A4/5 inducers or inhibitors
  • Prior enzalutamide within the last 4 weeks
  • DDI SUBSTUDY:
  • history of CHF or evidence of ventricular dysfunction
  • fructose intolerance
  • coadministration of CYP3A4 substrates

Treatment and study plan

Mervometostat (PF-06821497)

Drug

Oral continuous

Other names: EZH2i

Enzalutamide

Drug

Oral continuous

Other names: Xtandi

Itraconazole

Drug

Oral solution

Other names: Sporanox, Tolsura, Onmel

Primary outcomes

  1. Percentage of patients with dose limiting toxicities (DLTs) to determine the maximum tolerated dose (MTD)

    Time frame: Baseline up to 90 days

    First cycle DLTs will be utilized to determine the MTD

  2. Overall safety profile including adverse events

    Time frame: Baseline up to approximately 2 years

    Adverse Events will be graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version [4.03])

  3. Preliminary efficacy determination as evaluated by disease specific response criteria

    Time frame: Through study completion, approximately 2 years past last patient first visit.

    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.

  4. Overall safety profile including laboratory abnormalities

    Time frame: Baseline up to approximately 2 years

    Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version [4.03]), and timing.

  5. Overall safety profile including vital signs

    Time frame: Baseline up to approximately 2 years

    Vital sign changes from baseline including blood pressure, heart rate, ECG changes.

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

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

    PCWG3

Secondary outcomes

  1. Evaluate time to event anti-tumor activity of mevrometostat 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 frame: Baseline and every 21 days through time of confirmed disease progression, unacceptable toxicity, or through study completion, approximately 2 years.

    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)

  2. Evaluate overall survival

    Time frame: Baseline up to approximately 2 years

    Median time to death proportion of patients alive at 6 months, 1 year, and 2 years.

  3. Pharmacokinetic Parameters: Maximum Observed Plasma Concentration (Cmax)

    Time frame: At specific timepoints from Cycle 1 day 1 to End of Treatment visit

    Single dose and multiple dose PK will be calculated as data permits

  4. Pharmacokinetic Parameters: Time to Reach Maximum Observed Plasma Concentration (Tmax)

    Time frame: At specific timepoints from Cycle 1 day 1 to End of Treatment visit

    Single dose and multiple dose PK will be calculated as data permits

  5. Pharmacokinetic Parameters: Area Under the Curve (AUC)

    Time frame: At specific timepoints from Cycle 1 day 1 to End of Treatment visit

    Single dose and multiple dose PK will be calculated as data permits

  6. Pharmacokinetic Parameters: Apparent Oral Clearance (CL/F)

    Time frame: At specific timepoints from Cycle 1 day 1 to End of Treatment visit

    Single dose and multiple dose PK will be calculated as data permits

  7. Pharmacokinetic Parameters: Apparent Volume of Distribution (Vz/F)

    Time frame: At specific timepoints from Cycle 1 day 1 to End of Treatment visit

    Single dose and multiple dose PK will be calculated as data permits

  8. Pharmacokinetic Parameters: Plasma Decay Half-Life (t1/2)

    Time frame: At specific timepoints from Cycle 1 day 1 to End of Treatment visit

    Singe dose and multiple dose PK will be calculated as data permits

  9. Evaluate the impact of mevrometostat on patient reported outcomes.

    Time frame: At specific time-points from Cycle 1 Day 1 to End of Treatment visit.

    Quality of Life and Time to Functional Status Deterioration as assessed by FACT-P.

  10. Impact of mevrometostat in combination with enzalutamide, enzalutamide alone and mevrometostat alone on symptoms and symptomatic toxicity

    Time frame: At specific time points from Cycle1 Day 1 to end of treatment

    Questionnaire customized from PRO-CTCAE.

Study contacts

Contact information is provided by the study sponsor or research team.

Pfizer CT.gov Call Center

CONTACT

[email protected]

1-800-718-1021

Sponsors and collaborators

Lead sponsor

Pfizer

Industry

Registry information

Official study title

A PHASE I DOSE ESCALATION AND EXPANDED COHORT STUDY OF PF 06821497 (MEVROMETOSTAT) IN THE TREATMENT OF ADULT PATIENTS WITH RELAPSED/REFRACTORY SMALL CELL LUNG CANCER (SCLC), CASTRATION RESISTANT PROSTATE CANCER (CRPC) AND FOLLICULAR LYMPHOMA (FL)

Important dates

Study start
2018
Primary completion
2028
Study completion
2029
First posted
Mar 9, 2018
Registry last updated
Jul 9, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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