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

• ClinicalTrials.gov Identifier: NCT04104776
• Recruitment Status: Recruiting
• First Posted: September 26, 2019
• Last Update Posted: October 6, 2022
• Sponsor: Constellation Pharmaceuticals
• Information provided by (Responsible Party): Constellation Pharmaceuticals

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 (Clinical Trial)
• Estimated 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: September 18, 2019
• Estimated Primary Completion Date: December 31, 2025
• Estimated Study Completion Date: March 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 or other advanced/metastatic solid tumors (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 :

1. Phase 1: Frequency of Dose-limiting toxicities (DLTs) [ Time Frame: 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
2. Phase 2: Overall response rate (ORR) [ Time Frame: 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 :

1. Adverse events (AEs) and change in laboratory values [ Time Frame: 18 months ]
2. Area under the curve versus time (AUC) [ Time Frame: 18 months ]
3. Maximum observed plasma concentration (Cmax) [ Time Frame: 18 months ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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
• Histologically confirmed metastatic solid tumor (except ovarian clear cell cancer, endometrial cancer, and pleural or peritoneal mesothelioma)
• 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

Contacts

Contact: Medical Information; (844) 667-1992; medinfo@morphosys.com

Locations

United States, Georgia

Emory University Hospital; Recruiting

Atlanta, Georgia, United States, 30322

Contact: Kelsey Gates 404-727-3547 kelsey.gates@emoryhealthcare.org

Principal Investigator: R. Donald Harvey, MD

United States, Illinois

University of Chicago Medical Center; Recruiting

Chicago, Illinois, United States, 60637

Contact: Andrew McGettigan 773-702-1280 amcgettigan@medicine.bsd.uchicago.edu

Principal Investigator: Hedy Kindler, MD

United States, Maryland

University of Maryland - Marlene and Stewart Greenebaum Cancer Center; Recruiting

Baltimore, Maryland, United States, 21201

Contact: Margaret Carder 410-328-8611 Margaret.Carder@umm.edu

Principal Investigator: Yixing Jiang, M.D., Ph.D.

United States, Massachusetts

Massachusetts General Hospital; Recruiting

Boston, Massachusetts, United States, 02114

Contact: Catie Elsier 617-643-0425 celsier@mgh.harvard.edu

Principal Investigator: Ryan Sullivan, MD

Dana Farber Cancer Institute; Recruiting

Boston, Massachusetts, United States, 02215

Contact: Illy Dixon 617-632-5617 Illya_Dixon@dfci.harvard.edu

Principal Investigator: Leena Gandhi, MD

United States, Michigan

University of Michigan; Recruiting

Ann Arbor, Michigan, United States, 48109

Contact: Tiffanie Barnhizer 734-647-8901 barnhize@med.umich.edu

Principal Investigator: Tycel Phillips, MD

START Midwest; Recruiting

Grand Rapids, Michigan, United States, 49546

Contact: Shannon S Skibinski-Preston, MPH 616-954-5552 shannon.skibinski@startmidwest.com

Contact: Yvette Cole, RN 616-389-1652 yvette.cole@startmidwest.com

Principal Investigator: Nehal Lakhani, MD

United States, New Jersey

Hackensack University Medical Center; Recruiting

Hackensack, New Jersey, United States, 07601

Contact: Chelsea McCabe 551-996-4725 chelsea.mccabe@hackensackmeridian.org

Principal Investigator: Martin Gutierrez, MD

United States, New York

Montefiore Einstein Center for Cancer Care; Recruiting

Bronx, New York, United States, 10461

Contact: Mohammad Ghalib 718-405-4208 mhghalib@montefiore.org

Principal Investigator: Sanjay Goel, MD

NYU Langone Medical Center - Laura and Isaac Perlmutter Cancer Center; Recruiting

New York, New York, United States, 10016

Contact: Perla Arriola 347-630-0311 Perla.Arriola@nyulangone.org

Principal Investigator: Joshua Sabari, MD

United States, Ohio

University of Cincinnati Medical Center; Recruiting

Cincinnati, Ohio, United States, 45219

Contact: Bethany Fuhrman 513-584-8162 fuhrmaba@ucmail.uc.edu

Principal Investigator: Shuchi Gulati, MD

United States, Texas

START San Antonio; Recruiting

San Antonio, Texas, United States, 78229

Contact: Tiffany Lurati, RN 210-593-5290 Tiffany.Lurati@startsa.com

Contact: Carrie Choi, RN 210-593-2547 carrie.choi@startsa.com

Principal Investigator: Drew Rasco, MD

United States, Virginia

University of Virginia Cancer Center; Recruiting

Charlottesville, Virginia, United States, 22903

Contact: Anne Gabel 434-982-6657 AM7BD@hscmail.mcc.virginia.edu

Principal Investigator: Linda Duska,, MD

United States, Washington

Swedish Cancer Institute; Recruiting

Seattle, Washington, United States, 98104

Contact: Chun-Fang Qiu 206-215-6430 Chun-fang.Qiu@swedish.org

Principal Investigator: Charles Drescher, MD

Spain

Hospital Universitario de Salamanca; Recruiting

Salamanca, Castilla Y Leon, Spain, 37007

Contact: Magdalena Garcia 0034-616884422 mgarcia.ibsal@saludcastillayleon.es

Principal Investigator: Alejandro Martin Garcia-Sancho, MD, PhD

United Kingdom

Leicester Royal Infirmary; Not yet recruiting

Leicester, United Kingdom, LE1 5WW

Contact: Sarah Porter 0116-258-6687 sarah.porter@uhl-tr.nhs.uk

Principal Investigator: Harriet Walter

Sponsors and Collaborators

Constellation Pharmaceuticals

More Information

• Responsible Party: Constellation Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT04104776
• Other Study ID Numbers: 0209-01
• First Posted: September 26, 2019
• Last Update Posted: October 6, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Constellation Pharmaceuticals:

Lymphoma, Large B-Cell, Diffuse; Lymphoma, B-cell; Lymphoma, T-cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Site; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Irinotecan; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents

Additional relevant MeSH terms:

Lymphoma; Neoplasms; Lymphoma, Large B-Cell, Diffuse; Mesothelioma; Mesothelioma, Malignant; Prostatic Neoplasms; Lymphoma, T-Cell; Prostatic Neoplasms, Castration-Resistant; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases