Mevrometostat Treatment of Relapsed/Refractory SCLC, Castration Resistant Prostate Cancer, and Follicular Lymphoma
Conditions
Metastatic Castration Resistant Prostate Cancer (mCRPC), Small Cell Lung Cancer (SCLC), Follicular Lymphoma (FL)Drugs
Mervometostat (PF-06821497), EnzalutamideSummary
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
- Pfizer CT.gov Call Center
- 1-800-718-1021
- [email protected]
Study Director
- Pfizer CT.gov Call Center
Status
- RECRUITING
Central Contacts
- Pfizer CT.gov Call Center
- 1-800-718-1021
- [email protected]
Study Director
- Pfizer CT.gov Call Center
Status
- RECRUITING
Central Contacts
- Pfizer CT.gov Call Center
- 1-800-718-1021
- [email protected]
Study Director
- Pfizer CT.gov Call Center
Status
- RECRUITING
Central Contacts
- Pfizer CT.gov Call Center
- 1-800-718-1021
- [email protected]
Study Director
- Pfizer CT.gov Call Center
Status
- RECRUITING
Central Contacts
- Pfizer CT.gov Call Center
- 1-800-718-1021
- [email protected]
Study Director
- Pfizer CT.gov Call Center
Status
- RECRUITING
Central Contacts
- Pfizer CT.gov Call Center
- 1-800-718-1021
- [email protected]
Study Director
- Pfizer CT.gov Call Center
Status
- RECRUITING
Central Contacts
- Pfizer CT.gov Call Center
- 1-800-718-1021
- [email protected]
Study Director
- Pfizer CT.gov Call Center
Status
- RECRUITING
Central Contacts
- Pfizer CT.gov Call Center
- 1-800-718-1021
- [email protected]
Study Director
- Pfizer CT.gov Call Center
Status
- RECRUITING
Central Contacts
- Pfizer CT.gov Call Center
- 1-800-718-1021
- [email protected]
Study Director
- Pfizer CT.gov Call Center
Status
- RECRUITING
Central Contacts
- Pfizer CT.gov Call Center
- 1-800-718-1021
- [email protected]
Study Director
- Pfizer CT.gov Call Center
Status
- RECRUITING
Central Contacts
- Pfizer CT.gov Call Center
- 1-800-718-1021
- [email protected]
Study Director
- Pfizer CT.gov Call Center
Status
- RECRUITING
Central Contacts
- Pfizer CT.gov Call Center
- 1-800-718-1021
- [email protected]
Study Director
- Pfizer CT.gov Call Center
Status
- RECRUITING
Central Contacts
- Pfizer CT.gov Call Center
- 1-800-718-1021
- [email protected]
Study Director
- Pfizer CT.gov Call Center
Status
- RECRUITING
Central Contacts
- Pfizer CT.gov Call Center
- 1-800-718-1021
- [email protected]
Study Director
- Pfizer CT.gov Call Center
Status
- RECRUITING
Central Contacts
- Pfizer CT.gov Call Center
- 1-800-718-1021
- [email protected]
Study Director
- Pfizer CT.gov Call Center
Status
- RECRUITING
Central Contacts
- Pfizer CT.gov Call Center
- 1-800-718-1021
- [email protected]
Study Director
- Pfizer CT.gov Call Center
Status
- RECRUITING
Central Contacts
- Pfizer CT.gov Call Center
- 1-800-718-1021
- [email protected]
Study Director
- Pfizer CT.gov Call Center
Status
- RECRUITING
Central Contacts
- Pfizer CT.gov Call Center
- 1-800-718-1021
- [email protected]
Study Director
- Pfizer CT.gov Call Center
Status
- RECRUITING
Central Contacts
- Pfizer CT.gov Call Center
- 1-800-718-1021
- [email protected]
Study Director
- Pfizer CT.gov Call Center
Status
- RECRUITING
Central Contacts
- Pfizer CT.gov Call Center
- 1-800-718-1021
- [email protected]
Study Director
- Pfizer CT.gov Call Center
Status
- RECRUITING
Central Contacts
- Pfizer CT.gov Call Center
- 1-800-718-1021
- [email protected]
Study Director
- Pfizer CT.gov Call Center
Status
- RECRUITING
Central Contacts
- Pfizer CT.gov Call Center
- 1-800-718-1021
- [email protected]
Study Director
- Pfizer CT.gov Call Center
Status
- RECRUITING
Central Contacts
- Pfizer CT.gov Call Center
- 1-800-718-1021
- [email protected]
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 continuousDRUG:
EnzalutamideDescription:
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 continuousDRUG:
EnzalutamideDescription:
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 continuousDRUG:
EnzalutamideDescription:
Oral continuous
Outcome Measures
Primary Outcome Measures
Percentage of patients with dose limiting toxicities (DLTs) to determine the maximum tolerated dose (MTD)
Overall safety profile including adverse events
Preliminary efficacy determination as evaluated by disease specific response criteria
Overall safety profile including laboratory abnormalities
Overall safety profile including vital signs
Evaluate time to event mevrometostat and enzalutamide vs enzalutamide alone including radiographic prgression free survival
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.
Evaluate overall survival
Pharmacokinetic Parameters: Maximum Observed Plasma Concentration (Cmax)
Pharmacokinetic Parameters: Time to Reach Maximum Observed Plasma Concentration (Tmax)
Pharmacokinetic Parameters: Area Under the Curve (AUC)
Pharmacokinetic Parameters: Apparent Oral Clearance (CL/F)
Pharmacokinetic Parameters: Apparent Volume of Distribution (Vz/F)
Pharmacokinetic Parameters: Plasma Decay Half-Life (t1/2)
Evaluate the impact of mevrometostat on patient reported outcomes.
Impact of mevrometostat in combination with enzalutamide, enzalutamide alone and mevrometostat alone on symptoms and symptomatic toxicity
Timeline
Last Updated
November 1, 2024Start Date
March 9, 2018Today
February 5, 2025Completion Date ( Estimated )
December 9, 2025
Sponsors of this trial
Lead Sponsor
Pfizer