| Eligibility |
Inclusion Criteria:
Applicable to both arms:
1. Patients aged= 18 years (or legal age of majority in the jurisdiction) of age at the
time of informed consent
2. Ability to understand and provide written informed consent prior to undergoing any
study procedures
3. Life expectancy of > 3 months, as estimated by the Investigator
4. Presence of at least 1 measurable lesion using CT/MRI as defined by RECIST v1.1
5. Adequate haematological and organ function
- Haemoglobin =9.0 g/dL
- ANC =1.5 x 10^9/L
- Lymphocyte count =0.5 x 10^9/L
- Platelet count =100 x 10^9/L
- Total bilirubin =1.5 institutional ULN
- Serum albumin =2.5 g/dL
- Aspartate transaminase (AST)and alanine transaminase (ALT) =2.5 x ULN, unless
liver metastases are present in which case, they must be =5xULN
- Creatinine clearance >50 mL/min (calculated using the Cockcroft-Gault formula)
for patients with creatinine levels above institutional normal
- Patients not receiving anti-coagulant medication must have an INR of =1.5 and an
aPTT =1.5xULN
6. In the opinion of the Investigator, all other relevant medical conditions must be
well-managed and stable for =28days prior to first administration of study drug
7. Willing and able to participate in all required evaluations and procedures in this
study protocol
8. Contraception:
For female subjects: each female subject of childbearing potential must agree to use
two highly effective methods of contraception (ie, a method with less than 1% failure
rate per year [eg, sterilization, hormone implants, hormone injections, some
intrauterine devices, vasectomized partner, or combined birth control pills]) from
screening until 6 months after the last dose of EP0057 or olaparib, whichever was
taken last. Females of childbearing potential must have a negative serum pregnancy
test at Screening and a negative serum or urine pregnancy test within 24 hours before
each dose of EP0057 (and must not be lactating). Each female subject will be
considered to be of childbearing potential unless she has been surgically sterilized
by hysterectomy or bilateral tubal ligation/salpingectomy or has been postmenopausal
for =1 year. For male subjects: Sexually active male patients must be willing to use
barrier contraception (ie, condoms with spermicide) with all sexual partners for the
duration of the study and for 6months after the last EP0057 administration. Where a
sexual partner of a male participant is a 'woman of child-bearing potential', she must
use a highly effective method contraceptive measures (see above definition) during her
partner's participation in the study and for 6 months after her partner has received
his last dose of EP0057. Men must not donate sperm for 6 months after the last dose of
EP0057.
9. ECOG Performance Status Grade 0-2
Arm 1 (ATM-negative relapsed advanced GC) Specific Inclusion Criteria:
Patients must meet all of Arm 1-specific Inclusion Criteria and all of the Inclusion
Criteria applicable to both arms to be eligible for inclusion in the study:
10. Confirmed histological (cytological diagnosis excluded) of gastric adenocarcinoma or
gastro-oesophageal junction adenocarcinoma with archival tumour sample available. In
the absence of an archival tumour biopsy sample, a tumour biopsy will need to be
collected
11. HER2status known with no HER2 expression.PDL-1 status known (this does not need to be
known prior to enrolment)
12. ATM protein expression known by investigational use only immunohistochemical Ventana
ATM (Y170) assay, with ATM-negative status confirmed (defined as <25% nuclear
staining)
13. Relapse, defined as: clear, documented evidence of locally advanced or metastatic,
unresectable disease progression following: -two prior lines of systemic therapy,
providing patients have not received irinotecan in the second line setting OR One
prior line of therapy if considered to be unwilling or unsuitable for current standard
of care treatment options
Arm2 (Relapsed, extensive stage SCLC) Specific Inclusion Criteria:
Patients must meet all of Arm 2-specific Inclusion Criteria and all of the Inclusion
Criteria applicable to both arms to be eligible for inclusion in the study
14. Confirmed histological (cytological diagnosis excluded) SCLC with archival tumour
sample available. In the absence of an archival tumour biopsy sample, a tumour biopsy
will need to be collected. Note: Patients are eligible irrespective of prior
assessment of limited or extensive disease
15. PDL-1 status known (this does not need to be known prior to enrolment)
16. Relapse, defined as: clear, documented evidence of disease progression following at
least one (and no more than two) lines of previous therapy. Patients must have
received all available standard of care treatment options or be unsuitable or
unwilling to receive the current standard of care treatment
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
Arm 1 (ATM-negative relapsed advanced GC) Specific Exclusion Criteria:
25. Prior irinotecan in the second line setting
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