A Study of CPI-0209 in Patients With Advanced Tumors

Phase 1

• Conditions: advanced, solid, relapsed tumors / advanced tumors: human lymphomas / solid human tumor indications (urothelial carcinoma, ovarian clear cell cancer, endometrial carcinoma, GCB-DLBCL, small cell lung cancer, gastric or GEJ adenocarcinoma, serous ovarian cancer.; MedDRA version: 20.0Level: PTClassification code 10003899Term: B-cell lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: LLTClassification code 10064467Term: Urothelial carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10073269Term: Ovarian endometrioid carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: LLTClassification code 10033131Term: Ovarian carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

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

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-06-08
• Last Update Posted: 17 August 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 284

Inclusion Criteria

Eligible Phase 1 monotherapy and combination 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.
Eligible Phase 2 monotherapy patients in cohorts M1 to M3 are adults who are known to have the ARID1A mutation, have measurable disease per RECIST 1.1 and who have confirmed relapsed urothelial (M1), ovarian clear cell carcinoma (M2), or endometrial carcinoma (M3).
Eligible Phase 2 monotherapy patients in cohort M4 are adults who have relapsed or refractory GCB-DLBCL with at least 2 prior lines of standard therapy who are not considered candidates to receive CAR-T or ASCT therapy.
Eligible Phase 2 combination therapy patients in cohorts C1-C3 are adults who have measurable disease per RECIST 1.1 and who have confirmed small cell lung cancer (C1), gastric or GEJ adenocarcinoma (C2), or serous ovarian cancer (C3). All patients will have Eastern Cooperative Oncology Group (ECOG) performance status of = 1, absolute
neutrophil count (ANC) = 1.5 × 109/L, platelet count of = 100 × 109/L, and hemoglobin of = 9.0 g/dL.
All patients will have adequate renal function defined as creatinine clearance >40 mL/min or serum creatinine = 1.5 × ULN, and adequate hepatic function defined as serum total bilirubin = 1.5 × upper limit of normal (ULN), AST/ALT = 2.5 × ULN (or = 5 × ULN in patients with liver metastases); for patients in combination therapy (CPI-0209 +
irinotecan) serum total bilirubin = 1.5 ULN, or = 2.0 mg/dL, whichever is lower.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 142
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 142

Exclusion Criteria

1.Prev solid organ or hematopoietic cell transplant.
2.Known symptomatic untreated brain metastases. Pts with CNS metastases must have stable neurologic status following local therapy for at least 4 wks on stable or decreasing dose of steroid=10 mg daily prednisone (or equiv). Pts in the M4 lymphoma cohort won't be eligible if they have CNS involvement by lymphoma.
3.Clinically significant cardiovascular disease including: a. Myocardial infarction/stroke within 3 mths prior to Day 1; b. Unstable angina within 3 mths prior to Day 1; c. Congestive heart failure (CHF) or cardiomyopathy with NYHA Class 3 or 4; d. History of clinically significant ventricular arrhythmias; e. Uncontrolled hypertension (as 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 wks before starting study drug or not recovered from any effects of prior major surgery
5.Gl disorders ie, ulcerative colitis, malabsorption syndrome, refractory nausea and vomiting, biliary shunt, significant bowel resection, or other condition that may significantly interfere with absorption of the study medication by Investigator's assessment
6.Uncontrolled active infection requiring IV antibiotic, antiviral, or antifungal medications within 14 days before the 1st dose. Infections 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 2nd 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 w/o 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 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: a. 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 within 4 wks (or 5 half-lives), whichever is shorter, before the 1st dose (6 wks washout for nitrosoureas or mitomycin C); b. Previous treatment with an EZH2 inhibitor; c. Prior radiation therapy (including radiofrequency ablation) within 4 wks before 1st dose; d. Prior stereotactic body radiation therapy within 2 wks before first dose of study drug; e. Prior chemoembolization or radioembolization within 4 wks before 1st dose.
13.Concomitant medication(s) or food or beverage that are moderate or strong CYP3A inducers or in

Study & Design

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