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

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)

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.

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.

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