To investigate the effectiveness and tolerability of a second maintenance treatment in
participants with platinum-sensitivity relapsed (PSR) epithelial ovarian cancer, who have
previously received PARPi maintenance treatment and who have benefit (complete response [CR]
or partial response [PR]) or stable disease (SD) from further platinum based chemotherapy.
This is a Phase II, randomised, multicentre study to investigate the efficacy and
tolerability of a second maintenance treatment in participants with PSR epithelial ovarian
cancer, who have previously received PARPi maintenance treatment and who have benefit (CR or
PR) or SD from further platinum based chemotherapy.
Participants will be recruited globally from approximately 120 study sites in the USA,
Canada, Middle East and Europe.
Approximately 192 participants fulfilling all of the inclusion criteria and none of the
exclusion criteria will be randomised in a 1:1:1 ratio to the following 3 treatment arms (64
participants per arm):
- Arm 1 (ceralasertib+olaparib): Ceralasertib 160 mg once daily (QD) orally or per os (PO)
on Days 1 to 7 plus olaparib 300 mg twice daily (BD) PO continuous (28 day cycle)
- Arm 2 (olaparib monotherapy): Olaparib 300 mg BD PO daily continuous
- Arm 3 (placebo): Placebo to match olaparib BD PO daily continuous
The olaparib and placebo arms will be double blinded, whereas the ceralasertib+olaparib arm
will be open label. It is expected that approximately 320 participants will be screened.
The study achieved First Subject In date, but enrollment equals 0 as 7 participants have
signed the Informed Consent Form (ICF) and were later screen failed.
- Capable of providing signed informed consent, which includes compliance with the
requirements and restrictions listed in the ICF and in the Clinical Study Protocol
- Provision of signed and dated, written ICF prior to any mandatory study specific
procedures, sampling, and analyses.
- Female ≥18 years of age at the time of signing the ICF.
- Eastern Cooperative Oncology Group performance status 0 to 1 within 28 days of
- Participants with relapsed histologically confirmed diagnosis of high grade epithelial
ovarian cancer (including primary peritoneal and/or fallopian tube cancer), with
disease relapse on or after completion of PARPi maintenance therapy and who have not
received any intervening systemic treatment since discontinuation of PARPi (this
excludes the platinum based chemotherapy received during Screening Part 1 of this
- A minimum of 6 months of prior PARPi treatment received in the maintenance setting for
PSR ovarian cancer (a minimum of 12 months is required if the participant received
PARPi maintenance following first line chemotherapy). If the prior PARPi used was
olaparib then participants must have received treatment without significant toxicity
or the need for a permanent dose reduction.
- Disease relapse in the second line (first relapse) or third line (second relapse)
- Able to provide and consent to the collection of a contemporaneous tumor tissue biopsy
and blood sample.
- Able to provide a Formalin Fixed Paraffin Embedded archival tumour tissue block from
the time of primary tumour diagnosis (taken ideally prior to receiving any systemic
treatment, and definitely prior to first PARPi treatment) for prospective Breast
cancer susceptibility gene (BRCA) status testing. If tumour blocks are unavailable,
tissue sections are acceptable with a minimum requirement of at least 20 unstained
sections on uncharged slides without cover slips. Fine needle aspirates are not
- Where the patient has previously been tested for germline or somatic BRCA alterations
using a verified and well-validated test in line with local regulations, performed in
a locally accredited laboratory (eg, College of American Pathologists/Clinical
Laboratory Improvement Amendments laboratory, where available), and signed consent to
provide a copy of the BRCA report.
- Platinum-sensitive disease at the time of disease relapse, i.e, platinum-treatment
free survival of greater than 6 months as defined by the Gynecological Cancer
Intergroup (Wilson et al 2017).
- For the platinum-based chemotherapy course received following pre screening (Part 1)
and prior to entering the main screening (Part 2).
- Any prior palliative radiation must have been completed at least 7 days prior to the
start of study drugs, and participants must have recovered from any acute adverse
effects prior to the start of study treatment.
- Normal organ and bone marrow function measured within 28 days prior to randomization.
- Participant is willing and able to comply with the CSP for the duration of the study
including undergoing treatment and scheduled visits and examinations.
- Participants must have a life expectancy of ≥16 weeks.
- Participants must be able to swallow tablets whole.
- For inclusion in the optional (deoxyribonucleic acid) genetics research, study
participants must fulfil the following criterion:
Provide informed consent for the genetic sampling and analyses. If a participant declines
to participate in the genetics research, there will be no penalty or loss of benefit to the
participant. A participant who declines genetics research participation will not be
excluded from any other aspect of the main study.
- Participant's body weight must be >30 kg.
- Postmenopausal or evidence of non-childbearing status for women of childbearing
- Women of childbearing potential and their partners, who are sexually active, must
agree to the use of 2 highly effective forms of contraception in combination from the
signing of the informed consent (Screening Part 1), throughout the period of taking
study treatment and for at least 6 months after the last dose of study drug(s).
- Participants who have had drainage of their ascites during the final 2 cycles of their
last chemotherapy regimen or during the period between completion of chemotherapy and
first dose of study treatment.
- Participants with current signs or symptoms of bowel obstruction, including
sub-occlusive disease, related to underlying disease.
- History of leptomeningeal carcinomatosis.
- Participants with symptomatic uncontrolled brain metastases.
1. A scan to confirm the absence of brain metastases is not required.
2. Participants whose brain metastases have been treated may participate provided
they show radiographic stability. In addition, any neurologic symptoms that
developed either as a result of the brain metastases or their treatment must have
resolved or be stable (Common Terminology Criteria for Adverse Events [CTCAE]
Grade <2) either, without the use of steroids, or are stable on a steroid dose of
≤10 mg/day of prednisone or its equivalent and stable on anti convulsants if
required for at least 14 days prior to the start of treatment.
3. Participants with spinal cord compression are not eligible unless considered to
have received definitive treatment for this and have evidence of clinically SD
for >28 days and have not received steroid treatment for at least 14 days prior
to the start of study treatment.
- History of another primary malignancy except for:
1. Malignancy treated with curative intent and with no known active disease ≥5 years
before the first dose of IP and of low potential risk for recurrence;
2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
3. Adequately treated carcinoma in situ without evidence of disease.
- Major surgical procedures (as defined by the investigator) ≤28 days of beginning study
treatment, or minor surgical procedures ≤7 days. No waiting period required following
port a cath or other central venous access placement.
- Persistent toxicities (≥CTCAE Grade 2) caused by previous cancer therapy, excluding
alopecia and CTCAE Grade 2 peripheral neuropathy. Note: participants with signs of
ongoing complications from radiation therapy are not eligible for this study.
- Participants with myelodysplastic syndrome (MDS) /acute myeloid leukemia (AML) or with
features suggestive of MDS/AML.
- Resting electrocardiogram indicating uncontrolled, potentially reversible cardiac
conditions, as judged by the investigator, or participants with congenital long QT
- Known allergy or hypersensitivity to any of the study drugs or any of the study drug
- History of allogeneic organ transplantation including previous allogeneic bone marrow
transplant or double umbilical cord blood transplantation.
- History of active primary immunodeficiency.
- Active infection including tuberculosis (TB), hepatitis B (known positive hepatitis B
virus [HBV] surface antigen [HBsAg] result), hepatitis C (HCV), or human
immunodeficiency virus (HIV) (positive HIV 1/2 antibodies). Participants with a past
or resolved HBV infection are eligible. Participants positive for HCV antibody are
eligible only if polymerase chain reaction is negative for HCV ribonucleic acid.
- Uncontrolled intercurrent illness, including but not limited to, ongoing or active
infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
angina pectoris, uncontrolled cardiac arrhythmia, active interstitial lung disease,
serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric
- Current dependency on total parenteral nutrition or intravenous (iv) fluid hydration.
- Whole blood transfusions in the last 120 days prior to entry to the study.
- Cytotoxic chemotherapy, hormonal or non hormonal targeted therapy within 21 days of
Cycle 1, Day 1 is not permitted. The participant can receive a stable dose of
bisphosphonates or denosumab for bone metastases, before and during the study as long
as these were started at least 5 days prior to study treatment.
- Participation in another clinical study with an IP during the chemotherapy course
immediately prior to randomisation or during the course of the study.
- Previous treatment with ceralasertib or other ataxia telangiectasia and Rad3-related
protein, Checkpoint kinase 1 or deoxyribonucleic acid damage response inhibitor
- Exposure to a small molecule IP within 30 days or 5 half-lives (whichever is longer)
prior to randomization. The minimum washout period for immunotherapy and bevacizumab
shall be 42 days.
- Receipt of live attenuated vaccine within 30 days prior to the first dose of study
- Concomitant use of known strong cytochrome P450 (CYP) 3A inhibitors or moderate CYP3A
inhibitors. The required washout period prior to starting study treatment is 2 weeks.
- Concomitant use of known strong CYP3A inducers or moderate CYP3A inducers. The
required washout period prior to starting study treatment is 5 weeks for enzalutamide
or phenobarbital and 3 weeks for other agents.
- Involvement in the planning and/or conduct of the study (applies to Sponsor staff
and/or staff at the study site).
- Previous randomization in the present study.
- Judgment by the investigator that the participant should not participate in the study
if the participant is unlikely to comply with study procedures, restrictions and
- Pregnant or lactating women.