A Study of CPI-0209 in Patients With Advanced Solid Tumors and Lymphomas

Sponsor

Constellation Pharmaceuticals (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04104776

Collaborator

(none)

213

Enrollment

Locations

Arms

77.4

Anticipated Duration (Months)

13.3

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

First-in-human, open-label, sequential dose escalation and expansion study of CPI-0209 in patients with advanced solid tumors and lymphomas. CPI-0209 is a small molecule inhibitor of EZH2.

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumor Diffuse Large B Cell Lymphoma Lymphoma, T-Cell Mesothelioma, Malignant Prostatic Neoplasms, Castration-Resistant	Drug: CPI-0209	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

213 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1/2 Study of CPI-0209 in Patients With Advanced Solid Tumors and Lymphomas

Actual Study Start Date :

Sep 18, 2019

Anticipated Primary Completion Date :

Dec 31, 2025

Anticipated Study Completion Date :

Mar 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase 2 Cohort M1 CPI-0209 will be dosed once per day orally in 28 day cycles. • Cohort M1: Open to patients with urothelial carcinoma (with known ARID1A mutation)	Drug: CPI-0209 CPI-0209 alone
Experimental: Phase 2 Cohort M2 CPI-0209 will be dosed once per day orally in 28 day cycles. • Cohort M2: Open to patients with ovarian clear cell carcinoma (with known ARID1A mutation)	Drug: CPI-0209 CPI-0209 alone
Experimental: Phase 2 Cohort M3 CPI-0209 will be dosed once per day orally in 28 day cycles. • Cohort M3: Open to patients with endometrial carcinoma (with known ARID1A mutation)	Drug: CPI-0209 CPI-0209 alone
Experimental: Phase 2 Cohort M4 CPI-0209 will be dosed once per day orally in 28 day cycles. • Cohort M4: Open to patients with peripheral T-cell lymphoma (PTCL) and patients with diffuse large B-cell lymphoma (DLBCL), including patients with documented germinal center B cell like diffuse large B-cell lymphoma (GCB-DLBCL) with at least 1 EZH2 hotspot mutation	Drug: CPI-0209 CPI-0209 alone
Experimental: Phase 2 Cohort M5 CPI-0209 will be dosed once per day orally in 28 day cycles. • Cohort M5: Open to patients with relapsed or refractory malignant pleural or peritoneal mesothelioma with known BAP1 loss	Drug: CPI-0209 CPI-0209 alone
Experimental: Phase 2 Cohort M6 CPI-0209 will be dosed once per day orally in 28 day cycles. • Cohort M6: Open to patients with castration-resistant prostate cancer(mCRPC) with measurable soft tissue disease	Drug: CPI-0209 CPI-0209 alone

Outcome Measures

Primary Outcome Measures

Phase 1: Frequency of Dose-limiting toxicities (DLTs) [DLTs assessed during Cycle 1 (first 28 days on study)]
The maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of CPI-0209 in patients with advanced tumors
Phase 2: Overall response rate (ORR) [18 months]
Overall response rate (ORR) is defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR)

Secondary Outcome Measures

Adverse events (AEs) and change in laboratory values [18 months]
Area under the curve versus time (AUC) [18 months]
Maximum observed plasma concentration (Cmax) [18 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Phase 2:

Life expectancy of ≥ 12 weeks
ECOG 0-1
Adequate bone marrow function
Adequate renal function
Adequate liver function

For Cohort M1, the following criteria should be considered:

Histologically confirmed locally advanced unresectable or metastatic urothelial carcinoma with predominant urothelial histology
Known ARID1A mutation
Disease progression during or following prior chemotherapy
Measurable disease per RECIST 1.1

For Cohort M2, the following criteria should be considered:

Histologically confirmed advanced ovarian clear cell carcinoma
Known ARID1A mutation
Received at least 1 line of platinum-based chemotherapy
Measurable disease per RECIST 1.1
Patient must have disease progression after previously receiving effective and available standard of care treatment for clear cell ovarian cancer per local clinical practice

For Cohort M3, the following criteria should be considered:

Histologically or cytologically confirmed recurrent, metastatic, or unresectable endometrial carcinoma
Known ARID1A mutation
Received at least 1 line of platinum-based regimen in recurrent/metastatic setting
Documented microsatellite instability (MSI)-high or deficient mismatch repair (dMMR) tumors should have received, or not be considered eligible for therapy with an anti-PD-1 agent
Brachytherapy is allowed if completed >12 weeks before the first dose of study drug
Measurable disease per RECIST 1.1
Patients must have previously received effective and available standard of care treatment options for endometrial cancer per local clinical practice

For Cohort M4, the following criteria should be considered:

PTCL or DLBCL with the following criteria:
PTCL:
Documented refractory, relapsed, or progressive disease after at least 1 prior line of systemic therapy. Refractory is defined as:
Failure to achieve CR after first-line therapy
Failure to reach at least PR after second-line therapy or beyond
Must have at least 1 prior line of systemic therapy for PTCL.
Participants must be considered hematopoietic cell transplantation (HCT) ineligible during screening due to disease status (active disease), comorbidities, or other factors; the reason for HCT ineligibility must be clearly documented.
In the PTCL cohort, participants with anaplastic large cell lymphoma (ALCL) must have prior brentuximab vedotin treatment.
DLBCL:
Relapsed or refractory disease following 2 or more prior lines of standard therapy. A minimum of 5 patients with documented GCB-DLBCL with at least 1 EZH2 hotspot mutation will be enrolled.
Not considered candidates to receive CAR-T or autologous hematopoietic stem cell transplant (ASCT) as assessed by the treating investigator for reasons such as age, underlying comorbidities, or performance status, or due to disease progression after previously received ASCT or CAR-T. The reason for transplant ineligibility must be clearly documented.
For patients who underwent past ASCT or CAR-T treatment, at least 90 days must have elapsed since the start of the procedure. For all other patients, at least 8 weeks must have elapsed since their most recent systemic anti-DLBCL therapy

For Cohort M5, the following criteria should be considered:

Pleural or peritoneal relapsed/refractory mesothelioma
Must have progressed on or after at least 1 prior line of active therapy
Measurable disease per modified RECIST 1.1
Known BAP1 loss per immunohistochemistry (IHC) or NGS

For Cohort M6, the following criteria should be considered:

Have measurable soft-tissue disease
Documented metastatic disease
Disease progression while on prior therapies
Baseline testosterone ≤50 ng/dL (≤2.0 nM) and surgical or ongoing medical castration must be maintained throughout the duration of the study

For Cohort M6, the following criteria should be considered:

Bone-only disease without nodal disease and no evidence of visceral spread
Structurally unstable bone lesions concerning for impending fracture
Prior treatment with:
First generation AR antagonists within 4 weeks of study treatment
5α reductase inhibitors, ketoconazole, estrogens (including DES), or progesterones within 2 weeks of study treatment
No planned palliative procedures for alleviation of bone pain

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Emory University Hospital	Atlanta	Georgia	United States	30322
2	University of Chicago Medical Center	Chicago	Illinois	United States	60637
3	University of Maryland - Marlene and Stewart Greenebaum Cancer Center	Baltimore	Maryland	United States	21201
4	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
5	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
6	University of Michigan	Ann Arbor	Michigan	United States	48109
7	START Midwest	Grand Rapids	Michigan	United States	49546
8	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
9	Montefiore Einstein Center for Cancer Care	Bronx	New York	United States	10461
10	NYU Langone Medical Center - Laura and Isaac Perlmutter Cancer Center	New York	New York	United States	10016
11	University of Cincinnati Medical Center	Cincinnati	Ohio	United States	45219
12	START San Antonio	San Antonio	Texas	United States	78229
13	University of Virginia Cancer Center	Charlottesville	Virginia	United States	22903
14	Swedish Cancer Institute	Seattle	Washington	United States	98104
15	Hospital Universitario de Salamanca	Salamanca	Castilla Y Leon	Spain	37007
16	Leicester Royal Infirmary	Leicester		United Kingdom	LE1 5WW