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

Clinicaltrials.gov ID: NCT03460977
db-list-check Status RECRUITING
b-loader Phase PHASE1
b-people Age ≥ 18 Years
b-bullseye-arrow Enrollments 343

Conditions

Metastatic Castration Resistant Prostate Cancer (mCRPC), Small Cell Lung Cancer (SCLC), Follicular Lymphoma (FL)

Drugs

Mervometostat (PF-06821497), Enzalutamide

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.

Locations

23 locations Found with status Recruiting

Status

  • RECRUITING

Central Contacts

Study Director

  • Pfizer CT.gov Call Center

Status

  • RECRUITING

Central Contacts

Study Director

  • Pfizer CT.gov Call Center

Status

  • RECRUITING

Central Contacts

Study Director

  • Pfizer CT.gov Call Center

Status

  • RECRUITING

Central Contacts

Study Director

  • Pfizer CT.gov Call Center

Status

  • RECRUITING

Central Contacts

Study Director

  • Pfizer CT.gov Call Center

Status

  • RECRUITING

Central Contacts

Study Director

  • Pfizer CT.gov Call Center

Status

  • RECRUITING

Central Contacts

Study Director

  • Pfizer CT.gov Call Center

Status

  • RECRUITING

Central Contacts

Study Director

  • Pfizer CT.gov Call Center

Status

  • RECRUITING

Central Contacts

Study Director

  • Pfizer CT.gov Call Center

Status

  • RECRUITING

Central Contacts

Study Director

  • Pfizer CT.gov Call Center

Status

  • RECRUITING

Central Contacts

Study Director

  • Pfizer CT.gov Call Center

Status

  • RECRUITING

Central Contacts

Study Director

  • Pfizer CT.gov Call Center

Status

  • RECRUITING

Central Contacts

Study Director

  • Pfizer CT.gov Call Center

Status

  • RECRUITING

Central Contacts

Study Director

  • Pfizer CT.gov Call Center

Status

  • RECRUITING

Central Contacts

Study Director

  • Pfizer CT.gov Call Center

Status

  • RECRUITING

Central Contacts

Study Director

  • Pfizer CT.gov Call Center

Status

  • RECRUITING

Central Contacts

Study Director

  • Pfizer CT.gov Call Center

Status

  • RECRUITING

Central Contacts

Study Director

  • Pfizer CT.gov Call Center

Status

  • RECRUITING

Central Contacts

Study Director

  • Pfizer CT.gov Call Center

Status

  • RECRUITING

Central Contacts

Study Director

  • Pfizer CT.gov Call Center

Status

  • RECRUITING

Central Contacts

Study Director

  • Pfizer CT.gov Call Center

Status

  • RECRUITING

Central Contacts

Study Director

  • Pfizer CT.gov Call Center

Status

  • RECRUITING

Central Contacts

Study Director

  • Pfizer CT.gov Call Center

Eligibility Criteria

Key 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 Plan

Dose Escalation (Part 1A)

EXPERIMENTAL

Participants with SCLC, CRPC and FL will receive mevrometostat at escalating dose levels

  • DRUG:

    Mervometostat (PF-06821497)

    Description:

    Oral continuous

Dose Escalation (Part 1B)

EXPERIMENTAL

Participants with FL will receive mevrometostat at escalating dose levels

  • DRUG:

    Mervometostat (PF-06821497)

    Description:

    Oral continuous

Dose Escalation (Part 1C)

EXPERIMENTAL

Participants with mCRPC will receive PF-06821497 at escalating dose levels.

  • DRUG:

    Mervometostat (PF-06821497)

    Description:

    Oral continuous

Dose Escalation (Part 2A)

EXPERIMENTAL

Participants with mCRPC and SCLC will receive mevrometostat at escalating dose levels in combination with SOC.

  • DRUG:

    Mervometostat (PF-06821497)

    Description:

    Oral continuous
  • DRUG:

    Enzalutamide

    Description:

    Oral continuous

Dose Expansion (Part 2B)

EXPERIMENTAL

Participants with CRPC will receive mevrometostat in combination with SOC or SOC alone.

  • DRUG:

    Mervometostat (PF-06821497)

    Description:

    Oral continuous
  • DRUG:

    Enzalutamide

    Description:

    Oral continuous

Japan Cohort

EXPERIMENTAL

Participants with CRPC will receive mevrometostat at one or two doses

  • DRUG:

    Mervometostat (PF-06821497)

    Description:

    Oral continuous

China cohort

EXPERIMENTAL

Participants will receive mevrometostat at one or two doses

  • DRUG:

    Mervometostat (PF-06821497)

    Description:

    Oral continuous

Dose Expansion (Part 2C)

EXPERIMENTAL

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)

    Description:

    Oral continuous
  • DRUG:

    Enzalutamide

    Description:

    Oral continuous

Outcome Measures

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

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

Timeline

  • Last Updated
    November 1, 2024
  • Start Date
    March 9, 2018
  • Today
    February 5, 2025
  • Completion Date ( Estimated )
    December 9, 2025

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