Program Status
RecruitingPhase
Phase 1Prior Immunotherapy Allowed
NoCRC-directed Trial
NoDrugs
CPI-0209, CPI-0209Tags
MSI-H/ MMRd, MSS/ MMRpComments
“CPI-0209 is a second-generation EZH2 inhibitor that has been designed to achieve comprehensive target coverage through extended on-target residence time and enhanced potency compared with first-generation EZH2 inhibitors”
EZH2 that participates in histone methylation and, ultimately, transcriptional repression. This will lead to silenced gene function. This is the only trial that targets this in solid tumors, which could make it useful.
Location | Location Status |
---|---|
United States | |
Winship Cancer Institute of Emory University Atlanta, Georgia 30322 |
Recruiting |
University of Chicago Medical Center Chicago, Illinois 60637 |
Recruiting |
University of Maryland - Marlene and Stewart Greenebaum Cancer Center Baltimore, Maryland 21201 |
Completed |
Massachusetts General Hospital Boston, Massachusetts 02114 |
Recruiting |
Dana Farber Cancer Institute Boston, Massachusetts 02215 |
Recruiting |
University of Michigan Hospital Ann Arbor, Michigan 48109 |
Completed |
South Texas Accelerated Research Therapeutics (Start) - Midwest Location Grand Rapids, Michigan 49546 |
Recruiting |
Hackensack University Medical Center Hackensack, New Jersey 07601 |
Recruiting |
Montefiore Einstein Center for Cancer Care Bronx, New York 10461 |
Completed |
NYU Langone Medical Center - Laura and Isaac Perlmutter Cancer Center New York, New York 10016 |
Recruiting |
Weill Medical College of Cornell University New York, New York 10065 |
Completed |
University of Cincinnati Medical Center Cincinnati, Ohio 45219 |
Completed |
South Texas Accelerated Research Therapeutics San Antonio, Texas 78229 |
Recruiting |
University of Virginia Health System Charlottesville, Virginia 22903 |
Recruiting |
Swedish Cancer Institute Seattle, Washington 98104 |
Recruiting |
Fred Hutchinson Cancer Seattle, Washington 98109-1023 |
Recruiting |
France | |
Bergonie Institute Bordeaux 33000 |
Recruiting |
Oscar Lambret Center Lille 59020 |
Recruiting |
Leon Berard Center Lyon 69373 |
Recruiting |
Hospital North Nantes 44093 |
Recruiting |
Nantes University Hospital Center - Hotel Dieu Hospital (Satellite) Nantes 44093 |
Recruiting |
Nantes University Hospital Center - Hotel Dieu Hospital Nantes 44093 |
Recruiting |
Strasbourg Europe Institut of Cancerology Strasbourg 23025 |
Recruiting |
Gustave Roussy Villejuif 94805 |
Recruiting |
Italy | |
Irccs University Hospital of Bologna Bologna 40138 |
Recruiting |
Gruppo Humanitas - Humanitas Research Hospital - Cancer Center Milan 20089 |
Recruiting |
National Cancer Institute, IRCCS Milan 20133 |
Recruiting |
European Institute of Oncology (IEO), IRCCS Milan 20141 |
Recruiting |
University Polyclinic Foundation "Agostino Gemelli" - IRCCS Rome 00168 |
Recruiting |
Korea, Republic of | |
Keimyung University - Dongsan Medical Center Daegu 42601 |
Recruiting |
National Cancer Center Gyeonggi-do 10408 |
Recruiting |
Gachon University Gil Medical Center Incheon 21565 |
Recruiting |
Seoul National University Hospital Seoul 03080 |
Recruiting |
Severance Hospital, Yonsei University Health System Seoul 03722 |
Recruiting |
Asan Medical Center Seoul 05505 |
Recruiting |
Gangnam Severance Hospital Seoul |
Recruiting |
Poland | |
University Teaching Centre, Early Clinical Trials Unit Gdansk 80-214 |
Recruiting |
Polish Mother's Memorial Hospital-Research Institute Lodz |
Recruiting |
University Teaching Hospital in Poznan, Department of Gynecologic Oncology Poznan 60-569 |
Recruiting |
Medical Center Pratia Poznan Skorzewo, |
Recruiting |
Maria Sklodowska-Curie - National Research Institute of Oncology Warsaw |
Recruiting |
Spain | |
University Clinical Hospital of Salamanca Salamanca, Castilla Y Leon 37007 |
Recruiting |
University Hospital Complex of Santiago (CHUS) Santiago De Compostela, Galicia |
Recruiting |
University Hospital Vall d'Hebron Barcelona |
Recruiting |
University Hospital of Girona Dr. Josep Trueta Girona |
Recruiting |
University Clinic of Navarra - Madrid Madrid |
Recruiting |
University Hospital 12 de Octubre Madrid |
Recruiting |
University Hospital Quiron Madrid Madrid |
Recruiting |
University Hospital Son Espases Palma De Mallorca |
Recruiting |
University Clinic of Navarra - Pamplona Pamplona |
Recruiting |
University Hospital Virgen del Rocio (HUVR) Seville |
Recruiting |
Valencia Oncology Institute (IVO) Valencia |
Recruiting |
United Kingdom | |
Royal United Hospital Bath |
Recruiting |
University Hospitals of Leicester NHS Trust Leicester |
Recruiting |
Imperial College Healthcare NHS Trust London SW7 2AZ |
Recruiting |
Royal Marsden Hospital - Sutton Sutton |
Recruiting |
Musgrove Park Hospital Taunton |
Recruiting |
Contacts
Inclusion Criteria
Inclusion Criteria:
Phase 1
Eligible Phase 1 patients are adults who have a confirmed locally advanced or metastatic tumors (solid tumors or lymphoma) that have relapsed following standard therapy or progressed through standard therapy or who have a disease for which no standard effective therapy exists.
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 (NGS testing)
* Disease progression during or following prior chemotherapy approved therapies or for which no standard therapy exists
* 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 (by NGS testing)
* Received at least 1 line of platinum-based chemotherapy and must have received bevacizumab as part of any line of treatments unless contraindicated or locally not approved or locally not accessible
* 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 (by NGS testing)
* Received at least 1 line of platinum-based regimen in recurrent/metastatic setting
* Documented microsatellite instability (MSI)-high or deficient mismatch repair (dMMR) or patients who have non-dMMR/microsatellite stable tumors should have received an anti-PD-1 or anti-PD-L1 agent alone or in combination with the approved agents as applicable, as part of their prior treatments unless considered not eligible, contraindicated or if not locally approved
* 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 unless these are contraindicated
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.
* 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, 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 for pleural mesothelioma or by RECIST 1.1 for peritoneal mesothelioma
* 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
Exclusion Criteria
Exclusion Criteria
Medical Conditions
* Previous solid organ or allogeneic hematopoietic cell transplant (HCT)
* Known symptomatic untreated brain metastases
* Clinically significant cardiovascular disease
* Major surgery within 4 weeks before starting study drug or not recovered from any effects of prior major surgery
* Gastrointestinal disorders or any other condition that may significantly interfere with absorption of the study medication by Investigator's assessment.
* Uncontrolled active infection requiring intravenous antibiotic, antiviral, or antifungal medications within 14 days before the first dose of study drug. Infections (eg, urinary tract infection) controlled on concurrent antimicrobial agents and antimicrobial prophylaxis per institutional guidelines are acceptable.
* Suspected pneumonitis or interstitial lung disease or a history of pneumonitis or interstitial lung disease.
* Have a history of a concurrent or second malignancy. Patients with a history of T-cell lymphoblastic lymphoma or T-Cell lymphoblastic leukemia are not eligible.
* Have current known active or chronic infection with HIV, hepatitis B, or hepatitis C. Screening of patients with serologic testing for these viruses is not required
* Clinically active or symptomatic viral hepatitis or chronic liver disease.
* Unstable or severe uncontrolled medical condition or any important medical or psychiatric illness or abnormal laboratory finding
* Previous solid organ or allogeneic hematopoietic cell transplant HCT.
Prior/Concomitant Therapy:
* Prior anticancer treatment:
* Prior systemic anticancer treatment with chemotherapy, targeted therapy, small molecule, antibody, or investigational anticancer therapy (includes prior PD-1 or PD-L1 therapy), or other anticancer therapeutic with the exception of gonadotropin releasing hormone analogues, within 4 weeks (or 5 half-lives), whichever is shorter, before the first dose of study drug (6 weeks washout for nitrosoureas or mitomycin C).
* Previous treatment with an EZH2 inhibitor
* Prior radiation therapy within 4 weeks before first dose of study drug
* Prior stereotactic body radiation therapy within 2 weeks before first dose of study drug
* Prior chemoembolization or radioembolization within 4 weeks before first dose of study drug.
* Concomitant medication(s) or food or beverage that are strong CYP3A inducers or inhibitors within 7 days prior to the first dose of study drug.
Other Exclusions
• Breastfeeding or pregnant woman or expecting to conceive or father children within the projected duration of the trial, starting with the Screening visit through 183 days after the last dose of study drug.
Cohort M6 (mCRPC) only
* Bone-only disease without nodal disease and no evidence of visceral spread
* Structurally unstable bone lesions concerning for impending fracture
* Herbal products that may decrease prostate-specific antigen within 4 weeks prior to Day 1 of treatment and while on study
* Treatment for prostate cancer (First generation androgen receptor antagonists within 4 weeks; 5α-reductase inhibitors, ketoconazole, estrogens, or progesterones within 2 weeks)
* Planned palliative procedures such as radiation therapy or surgery