Inclusion Criteria:
1. Has a histologically-confirmed metastatic or unresectable (Stage IV as defined by
American Joint Committee on Cancer (AJCC eighth edition) colorectal adenocarcinoma
(National Comprehensive Cancer Network [NCCN] 2018).
2. Has not progressed (ie, achieved a stable disease [SD], partial response [PR], or
complete response [CR]) after a first-line induction course of at least 6 cycles of
FOLFOX with bevacizumab as first-line therapy.
- Participants must not have received an investigational agent during their FOLFOX
+ bevacizumab induction course.
- Determination of SD/PR/CR will be made by the investigator.
- "First-line therapy" is defined as the first systemic chemotherapy regimen given
for the diagnosis of unresectable or metastatic CRC. Participants may have
received prior adjuvant/neoadjuvant chemotherapy for CRC, as long as it was
completed at least 6 months prior to initiation of first-line FOLFOX +
bevacizumab induction treatment.
3. Has experienced unacceptable toxicity to oxaliplatin that, in the opinion of the
treating physician, requires/required the discontinuation of oxaliplatin. Note: As an
example, unacceptable toxicity may include (but is not limited to) severe or prolonged
neurotoxicity.
• Participants must be randomized within a minimum of 2 weeks and a maximum of 6 weeks
after their last dose of FOLFOX + bevacizumab (last dose is the day of the last
infusion).
4. Has provided to the imaging contract research organization (iCRO) at least 1 set of
radiographic images taken during the FOLFOX + bevacizumab induction period and at
least 42 days prior to the imaging performed during screening. The iCRO must determine
the images are of diagnostic quality prior to randomization.
5. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within
10 days prior to randomization.
Exclusion Criteria:
1. Has known hypersensitivity to the components and/or excipients in bevacizumab, 5-FU or
olaparib.
2. Has known active central nervous system (CNS) metastases and/or carcinomatous
meningitis. Participants with previously treated brain metastases may participate
provided they are radiologically stable (ie, without evidence of progression for at
least 28 days by repeat imaging (note that the repeat imaging should be performed
during study screening), clinically stable and without requirement of steroid
intervention for at least 14 days prior to first dose of study intervention.
3. Has an active infection requiring systemic therapy.
4. Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is
required unless mandated by local health authority.
5. Has a known history of or is positive for hepatitis B surface antigen (HBsAg reactive)
or hepatitis C ribonucleic acid (HCV RNA [qualitative]) is detected). Note: No testing
for hepatitis B and hepatitis C is required unless mandated by local health authority.
6. Has a known psychiatric or substance abuse disorder that would interfere with the
participant's ability to cooperate with the requirements of the study.
7. Has myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) or with features
suggestive of MDS/AML.
8. Has hemoptysis or hematemesis within 28 days prior to randomization.
9. Has evidence of bleeding diathesis or significant coagulopathy (in the absence of
coagulation).
10. Has clinically significant bleeding within 28 days prior to randomization.
11. Is considered a poor medical risk due to a serious, uncontrolled medical disorder,
nonmalignant systemic disease or active, uncontrolled infection. Examples include, but
are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months)
myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord
compression, superior vena cava syndrome, extensive interstitial bilateral lung
disease on high-resolution computed tomography (HRCT) scan or any psychiatric disorder
that prohibits obtaining informed consent.
12. Has 1 or more conditions that, in the opinion of the treating physician, make the
participant ineligible for treatment with bevacizumab. These conditions may include:
- Uncontrolled hypertension (systolic blood pressure [SBP] >150 mm Hg or diastolic
blood pressure [DBP] >100 mm Hg) or a history of hypertensive crisis or
hypertensive encephalopathy
- History of nephrotic syndrome or moderate proteinuria
- History of gastrointestinal perforation
- History of non-gastrointestinal fistula formation
- History of possible reversible encephalopathy syndrome (RPLS)
13. Has received prior systemic anticancer therapy (other than FOLFOX + bevacizumab
induction) including investigational agents within 28 days prior to randomization.
Note: Participants must have recovered from all AEs due to previous therapies to
≤Grade 1 or baseline. Participants with persistent alopecia or Grade ≤3 neuropathy may
be eligible.
14. Has received prior therapy with olaparib or with any other polyadenosine
5'-diphosphoribose polymerase (PARP) inhibitor.
15. Is currently receiving either strong (eg, itraconazole, telithromycin, clarithromycin,
protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir,
nelfinavir, boceprevir, telaprevir) or moderate (eg, ciprofloxacin, erythromycin,
diltiazem, fluconazole, verapamil) inhibitors of cytochrome P450 3A4 (CYP3A4) that
cannot be discontinued for the duration of the study. The required washout period
prior to randomization is 2 weeks.
16. Is currently receiving either strong (phenobarbital, enzalutamide, phenytoin,
rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or
moderate (eg. bosentan, efavirenz, modafinil) inducers of CYP3A4 that cannot be
discontinued for the duration of the study. The required washout period prior to
randomization is 5 weeks for phenobarbital and 3 weeks for other agents.
17. Has undergone major surgery within 2 weeks of randomization or has not recovered
adequately from toxicities and/or complications from any major surgery prior to
randomization.
