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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04104776
Recruitment Status : Recruiting
First Posted : September 26, 2019
Last Update Posted : October 6, 2022
Sponsor:
Information provided by (Responsible Party):
Constellation Pharmaceuticals

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

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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


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




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 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04104776


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

Locations
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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
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Responsible Party: Constellation Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04104776    
Other Study ID Numbers: 0209-01
First Posted: September 26, 2019    Key Record Dates
Last Update Posted: October 6, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
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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
Prostatic Diseases