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

Pfizer

Status and phase: Enrolling; Phase 1

Conditions: Follicular Lymphoma (FL); Metastatic Castration Resistant Prostate Cancer (mCRPC); Small Cell Lung Cancer (SCLC)

Treatments: Drug: Enzalutamide; Drug: Mervometostat (PF-06821497)

Study type: Interventional

Funder types: Industry

Identifiers

NCT03460977

2023-509179-18-00 (Registry Identifier)

2018-001835-37 (EudraCT Number)

C2321001

Details and patient eligibility

About

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).

Full 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.

Enrollment: 343 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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343 participants in 8 patient groups

Dose Escalation (Part 1A)

Experimental group

Description:

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

Treatment:

Drug: Mervometostat (PF-06821497)

Dose Escalation (Part 1B)

Experimental group

Description:

Participants with FL will receive mevrometostat at escalating dose levels

Treatment:

Drug: Mervometostat (PF-06821497)

Dose Escalation (Part 1C)

Experimental group

Description:

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

Treatment:

Drug: Mervometostat (PF-06821497)

Dose Escalation (Part 2A)

Experimental group

Description:

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

Treatment:

Drug: Mervometostat (PF-06821497)

Drug: Enzalutamide

Dose Expansion (Part 2B)

Experimental group

Description:

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

Treatment:

Drug: Mervometostat (PF-06821497)

Drug: Enzalutamide

Japan Cohort

Experimental group

Description:

Participants with CRPC will receive mevrometostat at one or two doses

Treatment:

Drug: Mervometostat (PF-06821497)

China cohort

Experimental group

Description:

Participants will receive mevrometostat at one or two doses

Treatment:

Drug: Mervometostat (PF-06821497)

Dose Expansion (Part 2C)

Experimental group

Description:

Participants with mCRPC will receive mevrometostat at a different dose/dosing regimen than that of Part 2B in combination with SOC

Treatment:

Drug: Mervometostat (PF-06821497)

Drug: Enzalutamide