Mevrometostat Treatment of Relapsed/Refractory SCLC, Castration Resistant Prostate Cancer, and Follicular Lymphoma
18 Years and older, Male and Female
C2321001 (primary)
NCI-2018-01985
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).
Objectives
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.
Eligibility
- 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.
Treatment Sites in Georgia
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