Efficacy and Safety of Olaparib (MK-7339) With or Without Bevacizumab Compared to Bevacizumab With a Fluoropyrimidine in Unresectable or Metastatic Colorectal Cancer (CRC) (MK-7339-003/LYNK-003)

Completed · Phase 3

Conditions studied: Metastatic Colorectal Cancer

In brief

This is an efficacy and safety study of olaparib alone or in combination with bevacizumab being compared to bevacizumab with a fluoropyrimidine in participants with unresectable or metastatic colorectal cancer who have not progressed following first-line induction. The primary hypotheses are: Olaparib + Bevacizumab is superior to a fluoropyrimidine + Bevacizumab with respect to progression-free survival (PFS) using Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) as assessed by blinded independent central review (BICR); Olaparib is superior to a fluoropyrimidine + Bevacizumab with respect to PFS using RECIST 1.1 as assessed by BICR. As of amendment 5 study enrollment is being discontinued and study participants randomized to one of the two experimental arms (olaparib plus bevacizumab or olaparib monotherapy) must discontinue study intervention. Participants who are still on study treatment will no longer have tumor response assessments by BICR.

Key facts

Study ID: NCT04456699
Run by: Merck Sharp & Dohme LLC
People needed: 335
Starts: 2020-08-19
Expected to finish: 2023-11-06
Last updated by the study team: 2024-10-29

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

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).
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 folinic acid/fluorouracil/oxaliplatin (FOLFOX) + bevacizumab or 4 cycles of capecitabine and oxaliplatin (CAPOX) + bevacizumab as first-line therapy.
Participants must not have received an investigational agent during their induction course.
Determination of best overall response (SD/PR/CR) will be made by the investigator.
Non-Progressive Disease (PD) will be verified by BICR prior to randomization based on the images submitted to imaging contract research organization (iCRO) as described in inclusion criterion 4.
"First-line therapy" is defined as the first systemic chemotherapy regimen given for the diagnosis of unresectable or metastatic colorectal cancer (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 CAPOX + bevacizumab or FOLFOX + bevacizumab induction treatment.
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 CAPOX + bevacizumab or FOLFOX + bevacizumab (last dose is the day of the last infusion that contained oxaliplatin).
Has provided to the iCRO 1 set of baseline radiographic images taken before or during the CAPOX + bevacizumab or FOLFOX + bevacizumab induction period and at least 42 days prior to the imaging performed during Screening. Tumor imaging at Screening must be performed within 28 days prior to the date of randomization.
Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 10 days prior to randomization.

You may not qualify if…

Has known hypersensitivity to the components and/or excipients in bevacizumab, 5-FU, capecitabine, or olaparib.
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.
Has an active infection requiring systemic therapy.
Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority.
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.
Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
Has myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) or with features suggestive of MDS/AML.
Has hemoptysis or hematemesis within 28 days prior to randomization.
Has evidence of bleeding diathesis or significant coagulopathy (in the absence of anticoagulation).
Has clinically significant bleeding within 28 days prior to randomization.
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.
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
Arterial thromboembolic events (eg, myocardial infarction, cerebral infarction)
History of nephrotic syndrome or moderate proteinuria
History of gastrointestinal perforation
History of non-gastrointestinal fistula formation
History of possible reversible encephalopathy syndrome (RPLS)
Has received prior systemic anticancer therapy (other than CAPOX + bevacizumab or 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 are eligible.
Has received prior therapy with olaparib or with any other polyadenosine 5'-diphosphoribose polymerase (PARP) inhibitor.
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.
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.
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.

Where it is running

St Joseph Heritage Healthcare-Oncology ( Site 1383) — Fullerton, California, United States
UC Health Memorial Hospital ( Site 1401) — Colorado Springs, Colorado, United States
Poudre Valley Health System ( Site 1402) — Fort Collins, Colorado, United States
University Cancer & Blood Center, LLC ( Site 1381) — Athens, Georgia, United States
University of Chicago ( Site 1357) — Chicago, Illinois, United States
Illinois Cancer Care, PC ( Site 1352) — Peoria, Illinois, United States
James Graham Brown Cancer Center ( Site 1393) — Louisville, Kentucky, United States
University Medical Center New Orleans ( Site 1365) — New Orleans, Louisiana, United States
New England Cancer Specialists ( Site 1422) — Scarborough, Maine, United States
Cancer & Hematology Centers of Western Michigan ( Site 1358) — Grand Rapids, Michigan, United States
Hattiesburg Clinic Hematology/Oncology ( Site 1418) — Hattiesburg, Mississippi, United States
Washington University in St. Louis ( Site 1384) — St Louis, Missouri, United States
St. Vincent Frontier Cancer Center-Research ( Site 1414) — Billings, Montana, United States
CHI Health St. Francis ( Site 1406) — Grand Island, Nebraska, United States
Cancer Partners of Nebraska ( Site 1353) — Lincoln, Nebraska, United States
Providence Portland Medical Center ( Site 1400) — Portland, Oregon, United States
Oregon Health & Science University ( Site 1411) — Portland, Oregon, United States
Allegheny Singer Research Institute ( Site 1364) — Pittsburgh, Pennsylvania, United States
West Cancer Center - East Campus ( Site 1396) — Germantown, Tennessee, United States
Vanderbilt University Medical Center ( Site 1362) — Nashville, Tennessee, United States
Baylor Scott & White Medical Center - Temple ( Site 1397) — Temple, Texas, United States
Blue Ridge Cancer Care ( Site 1374) — Roanoke, Virginia, United States
St George Hospital ( Site 0052) — Kogarah, New South Wales, Australia
Liverpool Hospital ( Site 0055) — Liverpool, New South Wales, Australia
Providence Saint Joseph Medical Center, Disney Family Cancer ( Site 1392) — Burbank, California, United States

Full record on ClinicalTrials.gov

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