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

Program Status

Recruiting

Phase

Phase 1

Prior Immunotherapy Allowed

No

CRC-directed Trial

No

Drugs

CPI-0209, CPI-0209

Tags

MSI-H/ MMRd, MSS/ MMRp

Comments

“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

Medical Information
CONTACT
(844) 667-1992 medinfo@morphosys.com

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

NCT ID

NCT04104776

Date Trial Added

2019-09-26

Updated Date

2024-08-02