Investigation of 2X-121 in Patients With Advanced Ovarian Cancer Selected by the 2X-121 DRP®

Study Overview
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Brief Summary
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This study is to be performed as an open label, multicenter, single arm study of 2X-121 to evaluate anti-tumor efficacy of 2X-121 as single agent therapy in a 28-days cycle in advanced ovarian cancer patients. 2X-121 will be supplied for oral administration once daily as 600 mg (3 x 200 mg) capsules in a 28 days cycle. Patients with predicted high likelihood of responding to the drug (2X-121) using drug response prediction (DRP®), will be included in the study.

Official Title
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Phase II, Prospective Open Label, Single Arm Study to Investigate Anti-tumor Effect and Tolerability of 2X-121 in Patients With Advanced Ovarian Cancer Selected by the 2X-121 DRP®

Conditions
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Advanced Ovarian Cancer

Intervention / Treatment
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* Drug: 2X-121
* Device: 2X-121 DRP®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent form Age 18 years or older Histologically or cytological documented ovarian carcinoma with ≥ 2 or more previous chemotherapies including potential treatment with other PARP inhibitors (PARPi) Platinum free interval of ≥ 3 month Measurable disease by CT scan or MRI A 2X-121 DRP® using Fixed in Formalin and Embedded in Paraffin (FFPE) archival or the latest tumor tissue with an outcome measured as being in the upper 50% likelihood of response Performance status of ECOG ≤ 1 Patients must have a life expectancy of >16 weeks Recovered to Grade 1 or less from prior surgery or acute toxicities of prior radiotherapy, or treatment with cytotoxic, hormonal or biologic agents Adequate conditions and protocol values of the following clinical laboratory parameters: Absolute neutrophils count Hemoglobin Platelets Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) Serum bilirubin Alkaline phosphatase Creatinine Blood urea within normal limits FFPEs tumor tissue should be available either from primary surgery or later Negative serum pregnancy test in women of childbearing potential (WOCBP). Women of childbearing age and potential must be willing to use adequate effective contraception during the study and a period after last dose of study drug Exclusion Criteria: Currently participating in or having participated in a study of an investigational agent or using an investigational device within 2 weeks of giving informed consent Concurrent chemotherapy, radiotherapy, or hormonal therapy for the disease under investigation Other malignancy with exception of any stage I and II cancer that is deemed cured or deemed not to influence the overall survival by the Investigator Any active infection still requiring parenteral or oral antibiotic treatment Known HIV positivity Known active hepatitis B or C Clinical significant (i.e. active) cardiovascular disease: Stroke within ≤ 6 months prior to day 1 Transient ischemic attack (TIA) within ≤ 6 months prior to day 1 Myocardial infarction within ≤ 6 months prior to day 1 Unstable angina New York Hart Association (NYHA) Grade II or greater congestive heart failure (CHF) Serious cardiac arrhythmia requiring medication Other medications or conditions that in the investigator's opinion would contraindicate study participation of safety reasons or interfere with the interpretation of study results Inability to take oral medication, or malabsorption syndrome or any other uncontrolled gastrointestinal condition (e.g., nausea, diarrhoea, or vomiting) that might impair the bioavailability of 2X-121 Requiring immediate palliative treatment of any kind including surgery and/or radiotherapy Patients unable to be regularly followed for any reason (geographic, familiar, social, psychologic, housed in an institution eg. prison because of a court agreement or administrative order) Subjects that are depending on the sponsor/CRO or investigational site as well as on the investigator

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2X-121<br>Oral administration of 2X-121 once daily as 600 mg hard gelatin capsules in a 28 days cycle. | Drug: 2X-121<br>* Every patient will receive daily oral administrations of 3 x 200 mg 2X-121 hard gelatin capsules in a 28-day cycle.<br>* Other names: E7449, MGI25036;Device: 2X-121 DRP®<br>* A DRP is an assay that based on samples from a tumor can predict whether the tumor will respond to a specific drug or not.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | defined as complete response (CR) or partial response (PR) using the RECIST criteria version 1.1 | evaluated after up to approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical benefit rate (CBR) | defined as complete response (CR) and partial response (PR) or stable disease (SD) for > 16 weeks using the RECIST criteria version 1.1 | evaluated after up to approximately 2 years | 
| Progression free survival | from baseline to progression or death | evaluated after up to approximately 2 years | 
| Duration of response | from first response to progression | evaluated after up to approximately 2 years | 
| Overall survival | from baseline until death | evaluated after up to approximately 2 years | 
| Quality of Life measurement | evaluated by Quality of Life Questionnaires (QLQ) QLQ-C30 Version 3.0, EORTC QLQ-OV 28 and MOST Version 2.0 | at baseline and start of each cycle, up to approximately 2 years | 
| Correlation between 2X-121 DRP® and clinical outcome | comparing the DRP levels in the different response groups | evaluated after up to approximately 2 years |