CPI-0209 in Patients with Advanced Solid Tumors andLymphomas

Phase 1

• Conditions: advanced, solid, relapsed tumors / advanced tumors: human lymphomas / solid human tumor indications (urothelial carcinoma, or other advanced/metastatic solid tumors, ovarian clear cell cancer, endometrial carcinoma, lymphoma including peripheral T-cell Lymphoma and GCB-DLBCL, malignant pleural or peritoneal mesothelioma, metastatic castration - resistant prostate cancer (mCRPC)); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2020-004952-14-PL
• Lead Sponsor: Constellation Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-04-28
• Last Update Posted: 21 May 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 210

Inclusion Criteria

• Phase 1 patients: adults with confirmed locally advanced or metastatic tumors (solid tumors or lymphoma) who have relapsed after or progressed through standard therapy or who have a disease with no standard effective therapy
• Phase 2 patients, Cohort M1: adults with urothelial carcinoma (UC) or other advanced/metastatic solid tumors, except clear cell ovarian carcinoma (COCC), and endometrial carcinoma (EC):
• Only for UC:
a Histologically confirmed, locally advanced, unresectable or metastatic UC with predominant urothelial histology
b Known ARID1A mutation (NGS testing)
c If eligible for platinum-containing chemotherapy (PCC), must have PD during or following prior PCC, should have received prior PD1 or PD-L1 therapy. Patients unfit for cisplatin must have previously received carboplatin combination (and prior anti-PD1 or anti-PD-L1 therapy, as per local clinical practice).
d If not eligible for PCC, must have PD during or following prior anti-PD1 or anti-PD-L1 therapy
e Measurable disease per RECIST 1.1
• Only for other metastatic solid tumors:
a Histologically confirmed metastatic solid tumor with known ARID1A mutation (except COCC, EC, pleural or peritoneal mesothelioma)
b Known ARID1A mutation (NGS testing)
c Patient must have PD following approved therapies or for which no standard therapy exists (all countries), all available therapies have failed, and no therapies known to provide clinical benefit are available (France only)
d Measurable disease per RECIST 1.1
• Phase 2 patients, Cohort M2: adults with CCOC:
a Histologically confirmed advanced CCOC
b ARID1A mutation (NGS testing)
c Must have received min. 1 line of PCC and bevacizumab
d Measurable disease per RECIST 1.1
e Patient must have PD after receiving effective and available SoC treatment for CCOC
• Phase 2 patients, Cohort M3: adults with EC:
a Histologically or cytologically confirmed recurrent, metastatic, or unresectable EC
b Known ARID1A mutation (NGS testing)
c Min. 1 line of PCC in recurrent/metastatic setting
d Patients with documented MSI-high, dMMR or non-dMMR tumors should have received prior anti-PD-1 or anti-PD-L1 therapy
e Brachytherapy is allowed if completed more than 12 weeks before first dose of study drug
f Measurable disease per RECIST 1.1
g Patient must have received effective and available SoC treatment for EC. Patients with operable metastases in first relapse are not eligible and must undergo surgery; such patients are eligible with min. 4 weeks between the surgery and first dose of study drug and recovery from any effects of the surgery.
• Phase 2 patients, Cohort M4: adults with lymphoma: a Histologically confirmed PTCL or DLBCL with following criteria: PTCL:
• Documented refractory, relapsed, or PD after min. 1 prior line of systemic therapy. Refractory is defined as failure to: achieve CR after 1- line therapy, reach at least PR after 2-line therapy or beyond
• Must have min. 1 prior line of systemic therapy for PTCL.
o Patients must be considered HCT ineligible during screening due to disease status (active disease), comorbidities, or other factors
o In PTCL cohort, patients with 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 ASCT as assessed by the treating investigator for reasons such as age, underlying comorbidities, performance status, or due to PD after previousl

Exclusion Criteria

1. Previous solid organ or allogeneic HCT.
2. Known symptomatic untreated brain metastases. Patients with CNS metastases must have stable neurologic status following local therapy for at least 4 weeks on stable or decreasing dose of steroid = 10 mg daily prednisone (or equivalent). Patients in the M4 lymphoma cohort will not be eligible if they have known CNS involvement by lymphoma.
3. Clinically significant cardiovascular disease including:
a. Myocardial infarction/stroke within 3 months prior to Day 1 of treatment
b. Unstable angina within 3 months prior to Day 1 of treatment
c. Congestive heart failure or cardiomyopathy with New York Heart Association Class 3 or 4
d. History of clinically significant ventricular arrhythmias (eg, ventricular tachycardia, ventricular fibrillation, torsades de pointes)
e. Uncontrolled hypertension (as defined per institutional standards) despite 2 concomitant antihypertensive therapies
f. QT interval corrected by the Fridericia correction formula = 480 msec on the screening ECG
4. Major surgery within 4 weeks before starting study drug or not recovered from any effects of prior major surgery (uncomplicated central line placement or fine needle aspirate are not considered major surgery)
5. Gastrointestinal disorders ie, ulcerative colitis, malabsorption syndrome etc. or any other condition that may significantly interfere with absorption of the study medication by Investigator’s assessment.
6. 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.
7. Suspected pneumonitis or interstitial lung disease (confirmed radiography or CT) or a history of pneumonitis or interstitial lung disease
8. Have a history of a concurrent or second malignancy except for adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostate-specific antigen for = 1 year prior to randomization, adequately treated Stage 1 or 2 cancer currently in complete remission, or any other cancer that has been in complete remission for = 3 years. Patients with a history of t-cell lymphoblastic lymphoma or T-Cell lymphoblastic leukemia are not eligible.
9. Have current known active or chronic infection with HIV, hepatitis B, or hepatitis C
10. Clinically active or symptomatic viral hepatitis or chronic liver disease
11. Unstable or severe uncontrolled medical condition or any important medical or psychiatric illness or abnormal laboratory finding that would, in the Investigator’s judgment, increase the risk to the patient associated with his or her participation in the study
12. Prior anticancer treatment as follows:
a. Prior systemic anticancer treatment with chemotherapy, targeted therapy, small molecule, antibody, or investigational anticancer 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. For nitrosoureas or mitomycin C, 6 weeks washout is required. For prior PD1 or PD-L1 therapy, a washout period of at least 4 wee

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified