A Phase I/II Study of MEDI4736 in Combination With Olaparib in Patients With Advanced Solid Tumors.
MEDIOLA
2 other identifiers
interventional
264
7 countries
47
Brief Summary
The purpose of this study is to look at the effectiveness, safety, and antitumor activity of study drugs MEDI4736 in combination with olaparib (modules 1, 2, 3, 4, 5 and 7) and MEDI4736 in combination with olaparib and bevacizumab (module 6). It will also examine what happens to the study drugs in the body and investigate how well the combination between MEDI4736, olaparib and bevacizumab is tolerated.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Mar 2016
Longer than P75 for phase_1
47 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 17, 2016
CompletedStudy Start
First participant enrolled
March 17, 2016
CompletedFirst Posted
Study publicly available on registry
April 12, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 17, 2021
CompletedResults Posted
Study results publicly available
October 13, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
September 17, 2026
ExpectedApril 20, 2026
April 1, 2026
5.5 years
March 17, 2016
September 14, 2022
April 17, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Initial Stage Cohorts: Disease Control Rate (DCR) at Week 12
The DCR at 12 weeks was defined as the percentage of participants who had complete response (CR) + partial response (PR) + stable disease (SD) at 12 weeks. Participants demonstrated SD for a minimum interval of 11 weeks (minus 1 week to allow for an early assessment within the assessment window, i.e. 77 days) following the start of treatment. The DCR was determined using Investigator assessments according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
RECIST performed at baseline, at 4 weeks after first dose of olaparib monotherapy and every 8 weeks +/-7 days thereafter. Assessed until DCO 14 Jun 2019.
Second Stage Cohort: Objective Response Rate (ORR)
The ORR (based on RECIST 1.1 as assessed by the Investigator) was defined as the percentage of participants with at least 1 visit response of CR or PR prior to PD or last evaluable assessment in the absence of progression. The 95% confidence interval (CI) were calculated using Exact Clopper-Pearson confidence limits for the binomial proportion.
RECIST performed at baseline, and every 8 weeks +/-7 days thereafter. Assessed until 17 Sep 2021.
Second Stage Cohorts: DCR at Week 24
The DCR at 24 weeks was defined as the percentage of participants who had CR + PR + SD at 24 weeks. Participants demonstrated SD for a minimum interval of 23 weeks (minus 1 week to allow for an early assessment within the assessment window, i.e. 161 days) following the start of treatment. The DCR was determined using Investigator assessments according to RECIST v1.1.
RECIST performed at baseline, and every 8 weeks +/-7 days thereafter. Assessed until 17 Sep 2021.
Secondary Outcomes (15)
Second Stage Expansion Cohort: DCR at Week 24
RECIST performed at baseline, and every 8 weeks +/-7 days thereafter. Assessed until 17 Sep 2021.
Initial Stage Cohorts: DCR at Week 28
RECIST performed at baseline, at 4 weeks after first dose of olaparib monotherapy and every 8 weeks +/-7 days thereafter. Assessed until DCO 14 Jun 2019.
Second Stage Cohorts: DCR at Week 56
RECIST performed at baseline, and every 8 weeks +/-7 days thereafter. Assessed until 17 Sep 2021.
Initial and Second Stage Cohorts: ORR
RECIST performed at baseline, at 4 weeks after first dose of olaparib monotherapy (for initial stage cohort only) and every 8 weeks +/-7 days thereafter. Assessed until DCO 14 Jun 2019 and 17 Sep 2021 for initial and second stage cohorts, respectively
Initial and Second Stage Cohorts: Duration of Response (DoR)
RECIST performed at baseline, at 4 weeks after first dose of olaparib monotherapy (for initial stage cohort only) and every 8 weeks +/-7 days thereafter. Assessed until DCO 14 Jun 2019 and 17 Sep 2021 for initial and second stage cohorts, respectively
- +10 more secondary outcomes
Study Arms (3)
Arm 1
EXPERIMENTALIncludes initial stage cohorts (modules 1 to 4): Olaparib twice daily starting on week 1 day 1 and MEDI4736 every 4 weeks starting on week 5 day 1
Arm 2
EXPERIMENTALIncludes 2nd stage cohorts (modules 5 \& 7): Olaparib twice daily starting on week 1 day 1 and MEDI4736 every 4 weeks starting on week 1 day 1
Arm 3
EXPERIMENTALIncludes 2nd stage cohort (module 6): Olaparib twice daily starting on week 1 day 1 / MEDI4736 every 4 weeks starting on week 1 day 1 / Bevacizumab every 2 weeks starting on week 1 day 1
Interventions
Eligibility Criteria
You may qualify if:
- Patients must have histologically or cytologically confirmed progressive advanced or metastatic solid tumor of one of the following:
- Platinum sensitive relapsed small cell lung cancer (module 1)
- gBRCAm HER2-negative metastatic breast cancer (module 2)
- gBRCAm ovarian cancer (modules 3 and 5)
- Metastatic or relapsed Gastric cancer (adenocarcinoma) (module 4)
- gBRCAm negative ovarian cancer (modules 6 and 7)
- At least one measurable lesion that can be accurately assessed at baseline by computed tomography (CT) (or magnetic resonance imaging \[MRI\] suitable for assessment as per RECIST 1.1. The baseline scan must be obtained within 28 days prior to the first dose of olaparib.
- Male or female patients, age ≥18 years (≥19 years for South Korea)
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Life expectancy ≥12 weeks
- Adequate organ and marrow function
- Ability to swallow oral medications (capsules and tablets) without chewing, breaking, crushing, opening or otherwise altering the product formulation. Patients should not have gastrointestinal illnesses that would preclude the absorption of olaparib, which is an oral agent. For the gastric cancer cohort, patients with a full or partial gastrectomy will be permitted.
- Ability of patient to understand and the willingness to sign a written informed consent document prior to any protocol related procedures, including screening evaluations.
- Female patients must either:
- Be of non-reproductive potential OR
- +1 more criteria
You may not qualify if:
- Prior chemotherapy or other systemic anticancer therapy within 4 weeks prior to start of olaparib treatment, 6 weeks for nitrosoureas or mitomycin. Exceptions include: Anti-hormonal treatment for ER positive or PR positive breast cancer is allowed until 7 days prior to treatment with olaparib, exposure to an investigational agent within 30 days or 5 half-lives (whichever is the longer) prior to start of olaparib treatment is not allowed, prior receipt of biologics targeting T cell co-regulatory proteins and/or immune checkpoints is not allowed. Examples include MEDI4736 or other PD1 or PD-L1 or PD-L2 inhibitors or anti-CTLA4 therapy, previous treatment with a PARP inhibitor, is not allowed.
- Radiation therapy within 4 weeks prior to start of olaparib treatment (includes radiation targeting bone metastases) or radionuclide treatment within 6 weeks of treatment start.
- Current dependency on total parenteral nutrition or IV fluid hydration.
- Concomitant use of known strong cytochrome P450 (CYP) 3A (CYP3A) inhibitors or moderate CYP3A inhibitors. Concomitant use of known strong or moderate CYP3A inducers.
- Concomitant therapy with any other anticancer therapy or chronic use of systemic corticosteroids.
- Previous allogenic bone marrow transplant or double umbilical cord blood transplantation
- Whole blood transfusions in the last 120 days
- Patients with symptomatic or uncontrolled brain metastases.
- Patients being considered at poor medical risk due to a serious, uncontrolled medical disorder or non-malignant systemic disease.
- Any psychiatric disorder that prohibits obtaining informed consent
- Major surgery or significant traumatic injury within 2 weeks of run-in
- Immunocompromised patients
- QTc prolongation \>470 msec or other significant ECG abnormality noted within 14 days of treatment
- Pregnant and breastfeeding women are excluded.
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
- IQVIA Pty Ltdcollaborator
Study Sites (47)
Research Site
Newnan, Georgia, 30265, United States
Research Site
Towson, Maryland, 21204, United States
Research Site
Boston, Massachusetts, 02114, United States
Research Site
Detroit, Michigan, 48202, United States
Research Site
St Louis, Missouri, 63110, United States
Research Site
Hilliard, Ohio, 43026, United States
Research Site
Philadelphia, Pennsylvania, 19104, United States
Research Site
Bordeaux, 33076, France
Research Site
Caen, 14076, France
Research Site
Clermont-Ferrand, 63011, France
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Dijon, 21079, France
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Marseille, 13385, France
Research Site
Nantes, 44202, France
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Paris, 75014, France
Research Site
Pierre Benit Cedex, 69495, France
Research Site
Toulouse, 31059, France
Research Site
Villejuif, 94805, France
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Haifa, 91096, Israel
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Jerusalem, 91031, Israel
Research Site
Petah Tikva, 49100, Israel
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Ramat Gan, 5265601, Israel
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Tel Aviv, 6423906, Israel
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Amsterdam, 1066 CX, Netherlands
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Amsterdam, 1081 HV, Netherlands
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Maastricht, 6229 HX, Netherlands
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Nijmegen, 6525 GA, Netherlands
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Rotterdam, 3075 EA, Netherlands
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Utrecht, 3584 CX, Netherlands
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Goyang-si, 10408, South Korea
Research Site
Seongnam-si, 13620, South Korea
Research Site
Seoul, 03080, South Korea
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Seoul, 03722, South Korea
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Seoul, 05505, South Korea
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Seoul, 06273, South Korea
Research Site
Seoul, 06591, South Korea
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Seoul, 135-710, South Korea
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Chur, CH-7000, Switzerland
Research Site
Lausanne, 1011, Switzerland
Research Site
Cambridge, CB2 0QQ, United Kingdom
Research Site
Dundee, DD1 9SY, United Kingdom
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Glasgow, G12 0YN, United Kingdom
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Greater London, SW3 6JJ, United Kingdom
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London, NW1 2PG, United Kingdom
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London, SE1 9RY, United Kingdom
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Manchester, M20 4BX, United Kingdom
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Newcastle upon Tyne, NE7 7DN, United Kingdom
Research Site
Sutton, SM2 5PT, United Kingdom
Related Publications (3)
Drew Y, Kim JW, Penson RT, O'Malley DM, Parkinson C, Roxburgh P, Plummer R, Im SA, Imbimbo M, Ferguson M, Rosengarten O, Steeghs N, Kim MH, Gal-Yam E, Tsoref D, Kim JH, You B, De Jonge M, Lalisang R, Gort E, Bastian S, Meyer K, Feeney L, Baker N, Ah-See ML, Domchek SM, Banerjee S; MEDIOLA Investigators. Olaparib plus Durvalumab, with or without Bevacizumab, as Treatment in PARP Inhibitor-Naive Platinum-Sensitive Relapsed Ovarian Cancer: A Phase II Multi-Cohort Study. Clin Cancer Res. 2024 Jan 5;30(1):50-62. doi: 10.1158/1078-0432.CCR-23-2249.
PMID: 37939124DERIVEDStaniszewska AD, Armenia J, King M, Michaloglou C, Reddy A, Singh M, San Martin M, Prickett L, Wilson Z, Proia T, Russell D, Thomas M, Delpuech O, O'Connor MJ, Leo E, Angell H, Valge-Archer V. PARP inhibition is a modulator of anti-tumor immune response in BRCA-deficient tumors. Oncoimmunology. 2022 Jun 18;11(1):2083755. doi: 10.1080/2162402X.2022.2083755. eCollection 2022.
PMID: 35756843DERIVEDDomchek SM, Postel-Vinay S, Im SA, Park YH, Delord JP, Italiano A, Alexandre J, You B, Bastian S, Krebs MG, Wang D, Waqar SN, Lanasa M, Rhee J, Gao H, Rocher-Ros V, Jones EV, Gulati S, Coenen-Stass A, Kozarewa I, Lai Z, Angell HK, Opincar L, Herbolsheimer P, Kaufman B. Olaparib and durvalumab in patients with germline BRCA-mutated metastatic breast cancer (MEDIOLA): an open-label, multicentre, phase 1/2, basket study. Lancet Oncol. 2020 Sep;21(9):1155-1164. doi: 10.1016/S1470-2045(20)30324-7. Epub 2020 Aug 6.
PMID: 32771088DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Global Clinical Lead
- Organization
- AstraZeneca
Study Officials
- PRINCIPAL INVESTIGATOR
Susan Domchek, MD
Abramson Cancer Center, University of Pennsylvania
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
- Expanded Access
- Yes
Study Record Dates
First Submitted
March 17, 2016
First Posted
April 12, 2016
Study Start
March 17, 2016
Primary Completion
September 17, 2021
Study Completion (Estimated)
September 17, 2026
Last Updated
April 20, 2026
Results First Posted
October 13, 2023
Record last verified: 2026-04