| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| 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)) |
|
| E.1.1.1 | Medical condition in easily understood language |
| advanced solid tumors and lymphomas |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
Phase 1:
Determine maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of CPI-0209 as monotherapy in patients with advanced tumors
Phase 2:
Evaluate the antitumor activity of CPI-0209 as monotherapy in patients with selected advanced solid tumors and lymphomas |
|
| E.2.2 | Secondary objectives of the trial |
Phase 1:
- Characterize the safety and tolerability of CPI-0209 as monotherapy
- Characterize the pharmacokinetic (PK) and pharmacodynamic (PD) profile of CPI-0209 as monotherapy
- Evaluate the preliminary clinical activity of CPI-0209 as monotherapy in patients with advanced tumors
Phase 2:
- Further characterize the safety and tolerability of CPI-0209 as monotherapy in patients with selected advanced solid tumors and lymphomas
- Further characterize the PK and PD profile of CPI-0209 as monotherapy
- Assess the optimal dose for future clinical trials |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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 previously received ASCT or CAR-T
• For patients with past ASCT or CAR-T treatment, min. 90 days must have elapsed since start of the procedure. For all other patients, min 8 weeks must have elapsed since most recent systemic anti-DLBCL therapy b Min. 1 bi-dimensionally measurable lesion on imaging scan defined as > 1.5 cm in its longest dimension
• Phase 2 patients, Cohort M5: adults with relapsed/refractory malignant mesothelioma:
a Pleural or peritoneal relapsed/refractory mesothelioma
b Must have progressed on or after min. 1 prior line of active therapy
c Have measurable disease for pleural mesothelioma (modified RECIST 1.1) or for peritoneal mesothelioma (RECIST 1.1)
d. Known BAP1 loss per IHC or NGS
• Phase 2 patients, Cohort M6: adults with mCRPC:
a Have measurable soft-tissue disease with CT scan as defined by PCWG3 criteria
b Documented metastatic disease
c Progression while on prior therapies of ≥ 1 of ARSi and ≥ 1 taxane based chemotherapy; Taxane-based chemotherapy cabazitaxel (French version only); patients known to possess HRR mutation must have been treated with prior PARP inhibitor therapy
d Baseline testosterone levels must be ≤ 50 ng/dL (≤ 2.0 nM), surgical or ongoing medical castration must be maintained throughout duration of the study
All patients will have ECOG performance status of = 1 and adequate organ function. All patients and their partners with childbearing potential should agree to use at least 1 highly effective contraceptive method
|
|
| E.4 | Principal 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 weeks is acceptable. All toxicities of prior therapies must have resolved or are Grade 1 (except for endocrinopathies requiring medication, neuropathy, and alopecia, which must have resolved to Grade ≤ 2).
b. Previous treatment with an EZH2 inhibitor
c. Prior radiation therapy (including radiofrequency ablation) within 4 weeks before first dose of study drug drug; (NOTE: a single fraction of radiotherapy for palliation confined to one field IS permitted within 1 week prior to day 1 of treatment)
d. Prior stereotactic body radiation therapy within 2 weeks before first dose of study drug
e. Prior chemoembolization or radioembolization
13. Concomitant medication(s) or food or beverage that are strong
CYP3A inducers or inhibitors
14. Is breastfeeding or pregnant or expecting to conceive or father
children within the projected
duration of the trial.
15. Are unwilling or unable to comply with this study protocol or study requirements.
Additional for Cohort M6 only
16. Bone-only disease without nodal disease and no evidence of visceral spread.
17. Structurally unstable bone lesions concerning for implementing fracture
18. Herbal products that may decrease PSA levels
19. Treatment with any of the following for prostate cancer prior to Day
1 of treatment: a. First generation AR antagonists; b. 5α-reductase
inhibitors, ketoconazole, estrogens or progesterones
20. Planned palliative procedures for alleviation of bone pain |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Phase 1:
Dose limiting toxicities
Phase 2:
ORR, defined as proportion of patients with a best overall response of CR or PR, per Investigator assessment based on:
- RECIST 1.1 for patients with solid tumors including patients with
peritoneal mesothelioma
- 2014 Lugano criteria for patients with lymphoma
- modified RECIST 1.1 criteria for patients with pleural mesothelioma
- PCWG3 criteria and as determined by investigator assessment for patients with prostate cancer |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
Phase 1:
- AEs and change in laboratory values
- PK and PD parameters
- ORR, defined as proportion of patients with a best overall response of complete response (CR) or partial response (PR), per Investigator assessment based on RECIST 1.1 or applicable response criteria
- ORR per Gynecologic Cancer Intergroup (GCIG)-defined CA-125 response criteria (ovarian cancer patients)
- ORR per PCWG3 (in Phase 1 prostate cancer patients only)
- Progression-free Survival (PFS), defined as the time from first dose to confirmed disease progression or death
- DOR, defined as the time from the date of first response to the date of confirmed disease progression
- Time to response (TTR), defined as the time from first dose to date of first response
- Disease control rate, defined as the proportion of patients with a best overall response of CR, PR or stable disease (SD)
Phase 2:
- PFS, defined as the time from first dose to confirmed disease progression or death
- Time-to-progression
- DOR, defined as the time from the date of first response to the date of confirmed disease progression
- TTR, defined as the time from first dose to date of first response
- Disease control rate, defined as the proportion of patients with a best overall response of CR, PR or stable disease (SD) per cohort and CPI-0209 dose level
- ORR per GCIG-defined CA-125 response criteria (ovarian cancer patients)
- Overall survival (OS), defined as the time from first dose to death
- AEs and changes in laboratory values
- PK and PD parameters |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Yes |
| E.7.1.1 | First administration to humans | Yes |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 1 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 35 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Korea, Republic of |
| United Kingdom |
| United States |
| France |
| Italy |
| Poland |
| Spain |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | 10 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
| E.8.9.2 | In all countries concerned by the trial months | 10 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
