EP0057 in Combination With Olaparib in Relapsed Advanced Gastric Cancer and Small Cell Lung Cancer

Exclusion Criteria

• •Applicable to both arms:
• •1. Unresolved or unstable serious toxic side-effects of prior chemotherapy or radiotherapy, ie, Grade≥2 per CTCAE (v5.0) except fatigue, alopecia, infertility, or palliative radiotherapy within 6 weeks prior to start of study treatment
• •2. Known cerebral metastases or CNS involvement including leptomeningeal disease. SCLC patients should not have imaging older than 2 weeks prior to start of screening to exclude brain disease. For GC patients, imaging should not be older than 12 weeks prior to start of screening to exclude brain disease. Note: Any abnormal findings on brain imaging should be discussed with the Medical Monitor as part of the screening process
• •• Subjects with previously treated brain metastases are eligible to participate if: a) they are stable (no evidence of progression by imaging; same imaging modality \[MRI or computed tomography (CT) scan\] must be used for each assessment) for at least 28 days prior to the first dose of study drug; b) any neurologic symptoms returned to baseline; c) they have no evidence of new or enlarging brain metastases; d) they are not using corticosteroids for at least 7 days prior to the first dose of study drug.
• •3. Malignant disease other than that being treated in this study, with the following exceptions:
• •* Malignancies that were treated curatively and have not recurred within 2 years prior to study treatment
• •* Completely resected basal cell and squamous cell skin cancers
• •* Any malignancy considered to be indolent and that has never required therapy
• •* Completely resected carcinoma in situ of any type
• •4. Concurrent treatment with other systemic anti-cancer therapy or investigational anti-cancer drugs within 3 weeks (or 5 half-lives, whichever is longer), or 4 weeks for immunotherapy, prior to the start of study treatment
• •5. Prior treatment with a topoisomerase I inhibitor
• •6. History of stroke, transient ischemic attack, or myocardial infarction, within 6 months prior to C1D1
• •7. Uncontrolled pleural effusion, pericardial effusion or ascites requiring recurrent drainage procedures (as defined as once monthly or more frequently). N. B - patients with indwelling catheters (eg, PleurX) are allowed
• •8. Confirmed QTcF \> 470 ms on screening ECG or history of Torsades de pointes or history of congenital long QT syndrome
• •9. Any evidence of severe or uncontrolled systemic conditions (eg, severe hepatic impairment) or current unstable or uncompensated respiratory or cardiac conditions which makes it undesirable for the patient to participate in the study or which could jeopardize compliance with the protocol
• •10. Any other concurrent severe and/or uncontrolled medical or surgical condition which, in the view of the Investigator, could compromise the patient's participation in the study
• •11. Patients with active hepatitis infection (defined as having a positive HBsAg test at screening) or hepatitis C. Patients with past HBV infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen \[anti-HBc\], and surface antigen \[anti-HBs\] antibody test and no HBV DNA detectable without HBV therapy) are eligible. Patients positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA
• •12. Active infection with SARS-Cov-2. All patients should be tested for active SARS-Cov-2 infection with an approved diagnostic kit
• •13. Patients with active HIV infection or known history of HIV infection
• •14. Active infection requiring IV antibiotics within two weeks prior to treatment
• •15. Women who are pregnant, likely to become pregnant, breast-feeding or either unable to or refuse to use effective means of contraception during treatment
• •16. Any major surgical procedure (planned or anticipated) (in the Investigator's judgement) within 2weeks of the first dose of study treatment
• •17. Known contra-indications, hypersensitivity, or severe intolerance to topoisomerase I inhibitors or Olaparib or the excipients of EP0057 or olaparib
• •18. Patients with a history, or features suggestive, of bone marrow dysplasia, MDS, or AML
• •19. The patient is unable to swallow capsules and/or has a surgical or anatomical condition that precludes swallowing and absorbing oral medication on an ongoing basis
• •20. Concurrent treatment with potent inhibitors or inducers of CYP3A4.
• •21. Concurrent treatment with Coumadin (Warfarin)
• •22. Patients considered by the Investigator to be at a higher baseline risk for new onset cystitis (see Section 7.5.4)
• •23. Palliative radiotherapy (e.g., for pain or bleeding) within 6 weeks prior to enrolment or patients who have not completely recovered (Grade ≥ 2) from the effects of previous radiotherapy
• •24. Any other condition that would, in the Investigator's judgement, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures or interpretation of study results
• •25. Prior irinotecan in the second line setting