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

Phase 1

Recruiting

• Conditions: Follicular Lymphoma (FL); Small Cell Lung Cancer (SCLC); Metastatic Castration Resistant Prostate Cancer (mCRPC)
• Interventions: Drug: Mervometostat (PF-06821497); Drug: Enzalutamide

• Registration Number: NCT03460977
• Lead Sponsor: Pfizer

Brief Summary

A Phase 1 Dose Escalation and Expanded Cohort Study Of PF-06821497 (Mevrometostat) in Adult Patients With Relapsed/Refractory Small Cell Lung Cancer (SCLC), Castration Resistant Prostate Cancer (CRPC) And Follicular Lymphoma (FL).

Detailed Description

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 Part 1, Part 2 and the Japan and China monotherapy cohorts Part 1A will evaluate safety and target modulation of mevrometostat monotherapy in patients with SCLC, FL and CRPC. Mevrometostat will be administered as monotherapy in escalating doses to patients with FL (Part 1B) and mCRPC (Part 1C) to determine the monotherapy MTD. In Part 2A (dose escalation, RP2D finding for dose escalation), mevrometostat will be administered in combination with SOC to patients with mCRPC and SCLC. Japan and China monotherapy cohorts will evaluate the safety, antitumor activity and PK of single agent mevrometostat in Japanese and Chinese patients. In Part 2B (dose expansion), patients with mCRPC will be randomized (1:1 ratio) to receive either SOC or mevrometostat in combination with SOC. Part 2B will assess the efficacy of mevrometostat at the RP2D in combination with SOC in patients with mCRPC in comparison to SOC alone. Part 2C will explore the efficacy of mevrometostat given at a different dose/dosing regimen than 2B in combination with SOC in patients with mCRPC.

Study Timeline

• Study First Submitted: 2018-02-12
• Study First Submitted QC: 2018-03-02
• Study First Posted: 2018-03-09
• Study Start: 2018-04-17
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-07
• Last Update Posted: 2025-07-08
• Primary Completion: 2026-03-19
• Study Completion: 2026-03-19

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 343

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.

Key

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
China cohort	Mervometostat (PF-06821497)	Participants will receive mevrometostat at one or two doses
Dose Expansion (Part 2B)	Mervometostat (PF-06821497)	Participants with CRPC will receive mevrometostat in combination with SOC or SOC alone.
Dose Escalation (Part 1A)	Mervometostat (PF-06821497)	Participants with SCLC, CRPC and FL will receive mevrometostat at escalating dose levels
Dose Escalation (Part 1C)	Mervometostat (PF-06821497)	Participants with mCRPC will receive PF-06821497 at escalating dose levels.
Dose Expansion (Part 2B)	Enzalutamide	Participants with CRPC will receive mevrometostat in combination with SOC or SOC alone.
Dose Escalation (Part 2A)	Mervometostat (PF-06821497)	Participants with mCRPC and SCLC will receive mevrometostat at escalating dose levels in combination with SOC.
Japan Cohort	Mervometostat (PF-06821497)	Participants with CRPC will receive mevrometostat at one or two doses
Dose Escalation (Part 1B)	Mervometostat (PF-06821497)	Participants with FL will receive mevrometostat at escalating dose levels
Dose Escalation (Part 2A)	Enzalutamide	Participants with mCRPC and SCLC will receive mevrometostat at escalating dose levels in combination with SOC.
Dose Expansion (Part 2C)	Mervometostat (PF-06821497)	Participants with mCRPC will receive mevrometostat at a different dose/dosing regimen than that of Part 2B in combination with SOC
Dose Expansion (Part 2C)	Enzalutamide	Participants with mCRPC will receive mevrometostat at a different dose/dosing regimen than that of Part 2B in combination with SOC

Primary Outcome Measures

Name	Time	Method
Overall safety profile including adverse events	Baseline up to approximately 2 years	Adverse Events will be graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version \[4.03\])
Percentage of patients with dose limiting toxicities (DLTs) to determine the maximum tolerated dose (MTD)	Baseline up to 90 days	First cycle DLTs will be utilized to determine the MTD
Overall safety profile including vital signs	Baseline up to approximately 2 years	Vital sign changes from baseline including blood pressure, heart rate, ECG changes.
Preliminary efficacy determination as evaluated by disease specific response criteria	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.
Overall safety profile including laboratory abnormalities	Baseline up to approximately 2 years	Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version \[4.03\]), and timing.
Evaluate time to event mevrometostat and enzalutamide vs enzalutamide alone including radiographic prgression free survival	Baseline until disease progression or death or through study completion (approx 2 years)	PCWG3

Secondary Outcome Measures

Name	Time	Method
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.	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)
Pharmacokinetic Parameters: Time to Reach Maximum Observed Plasma Concentration (Tmax)	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
Pharmacokinetic Parameters: Apparent Volume of Distribution (Vz/F)	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
Pharmacokinetic Parameters: Plasma Decay Half-Life (t1/2)	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
Evaluate the impact of mevrometostat on patient reported outcomes.	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.
Pharmacokinetic Parameters: Area Under the Curve (AUC)	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
Evaluate overall survival	Baseline up to approximately 2 years	Median time to death proportion of patients alive at 6 months, 1 year, and 2 years.
Pharmacokinetic Parameters: Apparent Oral Clearance (CL/F)	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
Pharmacokinetic Parameters: Maximum Observed Plasma Concentration (Cmax)	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
Impact of mevrometostat in combination with enzalutamide, enzalutamide alone and mevrometostat alone on symptoms and symptomatic toxicity	At specific time points from Cycle1 Day 1 to end of treatment	Questionnaire customized from PRO-CTCAE.

Trial Locations

Locations (85)

Urological Associates of Southern Arizona, P.C .; 🇺🇸 Tucson, Arizona, United States

Banner-University Medical Center Tucson; 🇺🇸 Tucson, Arizona, United States

The University of Arizona Cancer Center-North Campus; 🇺🇸 Tucson, Arizona, United States

The University of Arizona Cancer Center; 🇺🇸 Tucson, Arizona, United States

Urological Associates of Southern Arizona, PC; 🇺🇸 Tucson, Arizona, United States

Pacific Cancer Medical Center INC; 🇺🇸 Anaheim, California, United States

City of Hope (City of Hope National Medical Center, City of Hope Medical Center); 🇺🇸 Duarte, California, United States

City of Hope Investigational Drug Services (IDS); 🇺🇸 Duarte, California, United States

Norwalk Hospital; 🇺🇸 Norwalk, Connecticut, United States

The University of Kansas Cancer Center, Investigational Drug Services; 🇺🇸 Fairway, Kansas, United States

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