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)

Study Identifier:
C2321001
CT.gov Identifier:
NCT03460977
EudraCT Identifier:
2018-001835-37
EU Trial (CTIS) Number:
2023-509179-18-00
Study Contact Information:
N/A
Recruiting

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Study Summary

To evaluate PF-06821497 + Enzalutamide in Patients with Prostate Cancer

Part 1A (escalation monotherapy) will assess PF 06821497 administered as a single agent twice daily in a continuous regimen to patients with advanced tumors (SCLC CRPC, DLBCL and FL).

Part 1B [escalation recommended Phase 2 dose (RP2D) finding - monotherapy] will determine the maximum tolerated dose (MTD) of monotherapy in FL (MTD1).

Part 2A (escalation RP2D finding -combination) will determine the MTD of the combination with SOC in patients with SCLC (cisplatin or carboplatin with etoposide, MTD2, MTD3) and CRPC (MTD4).

Part 2B (dose expansion) will assess the efficacy of PF 06821497 at the RP2D identified from the Part 2A, in combination with SOC in patients with SCLC (n=16 to 30 for the 2 combination regimens), and CRPC (n=8 to 20) in addition to as a single agent twice daily in patients with FL (n=8 to 20).

A modified toxicity probability interval method was used to determine maximum tolerated dose.

To evaluate the pharmacokinetics (PK), safety, and antitumor activity of PF-06821497, a potent and selective inhibitor of EZH2, in an ongoing phase I trial (NCT03460977) in patients (pts) with SCLC, CRPC, and FL as monotherapy and in combination with standard of care therapies.

To compare the safety and efficacy of twice-daily PF-06821497 in combination with E (160 mg daily) (treatment arm) versus E monotherapy (control arm) administered continuously in patients with mCRPC previously treated with abiraterone.

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Prostate
  • Small Cell Lung
  • Lymphoma
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    I
    Sex
    Female & Male
    Age
    18 - 86 Years
    Study Drug
  • Drug: Experimental: Dose Escalation (Part 1A) Participants with SCLC, CRPC and FL will receive mevrometostat at escalating dose levels Drug: Mervometostat (PF-06821497) Oral continuous Experimental: Dose Escalation (Part 1B) Participants with FL will receive mevrometostat at escalating dose levels Drug: Mervometostat (PF-06821497) Oral continuous Experimental: Dose Escalation (Part 1C) Participants with mCRPC will receive mevrometostat at escalating dose levels. Drug: Mervometostat (PF-06821497) Oral continuous Experimental: Dose Escalation (Part 2A) Participants with mCRPC and SCLC will receive mevrometostat at escalating dose levels in combination with SOC. Drug: Mervometostat (PF-06821497) Oral continuous Drug: Enzalutamide Oral continuous Experimental: Dose Expansion (Part 2B) Participants with CRPC will receive mevrometostat in combination with SOC or SOC alone. Drug: Mervometostat (PF-06821497) Oral continuous Drug: Enzalutamide Oral continuous Experimental: Japan Cohort Participants with CRPC will receive mevrometostat at one or two doses Drug: Mervometostat (PF-06821497) Oral continuous Experimental: China cohort Participants will receive mevrometostat at one or two doses Drug: Mervometostat (PF-06821497) Oral continuous Experimental: Dose Expansion (Part 2C) Participants with mCRPC will receive mevrometostat at a different dose/dosing regimen than that of Part 2B in combination with SOC Drug: Mervometostat (PF-06821497) Oral continuous Drug: Enzalutamide Oral continuous. Experimental: DDI Substudy
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Recruiting

    Requirements information
    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
    • 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.
    • Exclusion Criteria:
    • Part 3
    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
    • 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.

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Madrid, Spain (CIOCC)
    Madrid, Spain, 28050
    Investigator
    Irene Moreno
    Status
    Recruiting
    Condition(s) Treated at Site
    Prostate
    Small Cell Lung
    Lymphoma
    Location
    START Madrid, Spain (FJD)
    Madrid, Spain, 28040
    Investigator
    Victor Moreno Garcia
    Status
    Recruiting
    Condition(s) Treated at Site
    Prostate
    Small Cell Lung
    Lymphoma
    Location
    START Barcelona
    Barcelona, Spain, 08023
    Investigator
    Tatiana Hernandez Guerrero
    Status
    Recruitment Complete
    Condition(s) Treated at Site
    Prostate
    Small Cell Lung
    Lymphoma
    Location
    START Carolinas
    Myrtle Beach, SC, United States, 29572
    Investigator
    Neal Shore
    Status
    Recruiting
    Condition(s) Treated at Site
    Prostate
    Small Cell Lung
    Lymphoma