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

Official 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)

Overview

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.

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 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.

Interventions

• Drug Mervometostat (PF-06821497)
  Oral continuous
• Drug Enzalutamide
  Oral continuous
• Drug Itraconazole
  Oral solution

Primary outcome measures

• Percentage of patients with dose limiting toxicities (DLTs) to determine the maximum tolerated dose (MTD) [Time frame: Baseline up to 90 days]
• Overall safety profile including adverse events [Time frame: Baseline up to approximately 2 years]
• Preliminary efficacy determination as evaluated by disease specific response criteria [Time frame: Through study completion, approximately 2 years past last patient first visit.]
• Overall safety profile including laboratory abnormalities [Time frame: Baseline up to approximately 2 years]
• Overall safety profile including vital signs [Time frame: Baseline up to approximately 2 years]
• 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)]

Secondary outcome measures (10)

• 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.]
• Evaluate overall survival [Time frame: Baseline up to approximately 2 years]
• Pharmacokinetic Parameters: Maximum Observed Plasma Concentration (Cmax) [Time frame: At specific timepoints from Cycle 1 day 1 to End of Treatment visit]
• 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]
• Pharmacokinetic Parameters: Area Under the Curve (AUC) [Time frame: At specific timepoints from Cycle 1 day 1 to End of Treatment visit]
• Pharmacokinetic Parameters: Apparent Oral Clearance (CL/F) [Time frame: At specific timepoints from Cycle 1 day 1 to End of Treatment visit]
• Pharmacokinetic Parameters: Apparent Volume of Distribution (Vz/F) [Time frame: At specific timepoints from Cycle 1 day 1 to End of Treatment visit]
• Pharmacokinetic Parameters: Plasma Decay Half-Life (t1/2) [Time frame: At specific timepoints from Cycle 1 day 1 to End of Treatment visit]
• 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.]
• 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]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 44 centers

• Banner-University Medical Center Tucson — Tucson
• The University of Arizona Cancer Center-North Campus — Tucson
• The University of Arizona Cancer Center — Tucson
• Arizona Urology Specialists, PLLC — Tucson
• Pacific Cancer Medical Center INC — Anaheim
• City of Hope (City of Hope National Medical Center, City of Hope Medical Center) — Duarte
• City of Hope Investigational Drug Services (IDS) — Duarte
• Norwalk Hospital — Norwalk
• … and 36 more centers

Spain · 12 centers

• Institut Català d´Oncología (ICO)-H. Durán i Reynals — L'Hospitalet de Llobregat
• Consorcio Hospitalario Provincial de Castellon — Castellon
• Hospital Quironsalud Madrid — Pozuelo de Alarcón
• Hospital Quironsalud Barcelona — Barcelona
• Hospital Universitari Vall d'Hebron — Barcelona
• Hospital Clinic de Barcelona — Barcelona
• Hospital Universitario Ramon y Cajal — Madrid
• H.U. Fundación Jiménez Díaz — Madrid
• … and 4 more centers

Russia · 9 centers

• Private Medical Institution "Euromedservice" — Pushkin
• LLC "Neyro-klinika" — Moscow
• Moscow GBUZ "City clinical hospital n. a. S.P. Botkina" of Moscow health department — Moscow
• SBHI of Moscow City Clinical Hospital — Moscow
• Budgetary Healthcare Institution of Omsk region "Clinical Oncological Dispensary" — Omsk
• Federal State Budgetary Institution National Medical Research Center n.a. V.A. Almazov — Saint Petersburg
• Federal State Budgetary Institution National Medical Research Center for Oncology n.a. N.N — Saint Petersburg
• Saint Petersburg State Budgetary Healthcare Institution "City Clinical Oncological Dispens — Saint Petersburg
• … and 1 more center

China · 6 centers

• The First Affiliated Hospital of Guangzhou Medical University — Guangzhou
• Hunan Cancer Hospital — Changsha
• Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School — Nanjing
• Zhongda Hospital Southeast University — Nanjing
• West China Hospital, Sichuan University — Chengdu
• The First Affiliated Hospital of Wenzhou Medical University — Wenzhou

South Korea · 5 centers

• Seoul National University Bundang Hospital — Seongnam
• Seoul National University Hospital — Seoul
• Severance Hospital, Yonsei University Health System — Seoul
• Ewha Womans University Mokdong Hospital — Seoul
• Chungnam national university hospital — Daejeon

Poland · 4 centers

• Szpital Wojewódzki im. Mikołaja Kopernika w Koszalinie — Koszalin
• Centrum Badań Klinicznych Jagiellońskie Centrum Innowacji sp. z o.o. — Krakow
• Centrum Medyczne MEDYK — Rzeszów
• Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w W — Warsaw

Bulgaria · 1 center

• Specialized Hospital for Active Treatment of Oncology - Haskovo — Haskovo

Japan · 1 center

• National Cancer Center Hospital East — Kashiwa

Identifiers

NCT: NCT03460977 · C2321001 · EZH2 · 2023-509179-18-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗