Mevrometostat Treatment of Relapsed/Refractory SCLC, Castration Resistant Prostate Cancer, and Follicular Lymphoma
- Conditions
- Follicular Lymphoma (FL)Small Cell Lung Cancer (SCLC)Metastatic Castration Resistant Prostate Cancer (mCRPC)
- Interventions
- Drug: Mervometostat (PF-06821497)
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 343
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
- 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 (83)
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
The University of Kansas Clinical Research Center
🇺🇸Fairway, Kansas, United States
The University of Kansas Hospital
🇺🇸Kansas City, Kansas, United States
The University of Kansas Medical Center Medical Office Building
🇺🇸Kansas City, Kansas, United States
The University of Kansas Cancer Center - Indian Creek Campus
🇺🇸Overland Park, Kansas, United States
The University of Kansas Cancer Center
🇺🇸Westwood, Kansas, United States
Norton Cancer Institute Pharmacy, Downtown Pharmacy
🇺🇸Louisville, Kentucky, United States
Norton Cancer Institute Pharmacy
🇺🇸Louisville, Kentucky, United States
Norton Cancer Institute, Norton Healthcare Pavilion
🇺🇸Louisville, Kentucky, United States
Norton Hospital
🇺🇸Louisville, Kentucky, United States
Maryland Oncology Hematology, P.A.
🇺🇸Rockville, Maryland, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Oncology Hematology West, PC dba Nebraska Cancer Specialists
🇺🇸Omaha, Nebraska, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
John Theurer Cancer Center at Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
OU Medical Center Presbyterian Tower
🇺🇸Oklahoma City, Oklahoma, United States
Stephenson Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States
Carolina Urologic Research Center
🇺🇸Myrtle Beach, South Carolina, United States
Parkway Surgery Center
🇺🇸Myrtle Beach, South Carolina, United States
Tennessee Oncolgy, PLLC
🇺🇸Nashville, Tennessee, United States
Tennessee Oncology, PLLC
🇺🇸Nashville, Tennessee, United States
The Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
Texas Oncology - Austin Midtown
🇺🇸Austin, Texas, United States
University of Texas Southwestern Medical Center - Simmons Cancer Center
🇺🇸Dallas, Texas, United States
UT Southwestern Medical Center
🇺🇸Dallas, Texas, United States
UT Southwestern University Hospital - William P. Clements, Jr
🇺🇸Dallas, Texas, United States
UT Southwestern University Hospital - Zale Lipshy
🇺🇸Dallas, Texas, United States
US Oncology Investigational Product Center (IPC)
🇺🇸Irving, Texas, United States
US Oncology Investigational Products Center
🇺🇸Irving, Texas, United States
NEXT Oncology
🇺🇸San Antonio, Texas, United States
Virginia Cancer Specialists, PC
🇺🇸Fairfax, Virginia, United States
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
Specialized Hospital for Active Treatment of Oncology - Haskovo
🇧🇬Haskovo, Bulgaria
The First Affiliated Hospital of Guangzhou Medical University
🇨🇳Guangzhou, Guangdong, China
Hunan Cancer Hospital
🇨🇳Changsha, Hunan, China
Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School
🇨🇳Nanjing, Jiangsu, China
Zhongda Hospital Southeast University
🇨🇳Nanjing, Jiangsu, China
West China Hospital, Sichuan University
🇨🇳Cheng Du, Sichuan, China
The First Affiliated Hospital of Wenzhou Medical University
🇨🇳Wenzhou, Zhejiang, China
National Cancer Center Hospital East
🇯🇵Kashiwa, Chiba, Japan
Centrum Medyczne MEDYK
🇵🇱Rzeszow, Poland
Seoul National University Bundang Hospital
🇰🇷Seongnam, Kyǒnggi-do, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Seoul-teukbyeolsi [seoul], Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Seoul-teukbyeolsi [seoul], Korea, Republic of
Ewha Womans University Mokdong Hospital
🇰🇷Seoul, Seoul-teukbyeolsi [seoul], Korea, Republic of
Chungnam national university hospital
🇰🇷Daejeon, Taejǒn-kwangyǒkshi, Korea, Republic of
Szpital Wojewódzki im. Mikołaja Kopernika w Koszalinie
🇵🇱Koszalin, Poland
Centrum Diagnostyczne Affidea Koszalin
🇵🇱Koszalin, Poland
LUX MED Onkologia Sp. z o.o. Szpital Szamocka
🇵🇱Warszawa, Poland
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie
🇵🇱Warszawa, Poland
Private Medical Institution "Euromedservice"
🇷🇺Pushkin, Saint - Petersburg, Russian Federation
LLC "Neyro-klinika"
🇷🇺Moscow, Russian Federation
Moscow GBUZ "City clinical hospital n. a. S.P. Botkina" of Moscow health department
🇷🇺Moscow, Russian Federation
SBHI of Moscow City Clinical Hospital
🇷🇺Moscow, Russian Federation
Budgetary Healthcare Institution of Omsk region "Clinical Oncological Dispensary"
🇷🇺Omsk, Russian Federation
Federal State Budgetary Institution National Medical Research Center n.a. V.A. Almazov
🇷🇺Saint Petersburg, Russian Federation
Saint Petersburg State Budgetary Healthcare Institution "City Clinical Oncological Dispensary"
🇷🇺Saint Petersburg, Russian Federation
Non-governmental Healthcare Institution ¨Railway Clinical Hospital of JSC ¨Russian Railways¨
🇷🇺Saint-Petersburg, Russian Federation
Federal State Budgetary Institution National Medical Research Center for Oncology n.a. N.N.
🇷🇺Saint-Petersburg, Russian Federation
State Budgetary Healthcare Institution of the Yaroslavl Region
🇷🇺Yaroslavl, Russian Federation
Institut Català d´Oncología (ICO)-H. Durán i Reynals
🇪🇸L'Hospitalet de Llobregat, Barecelona, Spain
Hospital Quironsalud Madrid
🇪🇸Pozuelo de Alarcon, Madrid, Spain
Hospital Quironsalud Barcelona
🇪🇸Barcelona, Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Consorcio Hospitalario Provincial de Castellon
🇪🇸Castellon, Spain
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
H.U. Fundación Jiménez Díaz
🇪🇸Madrid, Spain
Hospital Universitario 12 De Octubre
🇪🇸Madrid, Spain
Hospital Universitario HM Sanchinarro
🇪🇸Madrid, Spain
Hospital Universitario Virgen de la Victoria
🇪🇸Malaga, Spain
Hospital Universitari i Politecnic La Fe
🇪🇸València, Spain