OvarianPhase 1/2MEDIOLANCT02734004
A Phase I/II Study of MEDI4736 in Combination With Olaparib in Patients With Advanced Solid Tumors.
A Phase 1/2 study testing Olaparib, MEDI4736 and Bevacizumab in people with Ovarian and Breast, run by AstraZeneca at 47 sites in 7 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 130 years
- What is being tested?
- Olaparib, MEDI4736 and Bevacizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 264 participants
- Where
- 47 sitesin 7 countries
- Study dates
- 17 Mar 2016to 17 Sep 2026
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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
- Have a negative serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on Day 1, and agree to use contraception if they or their partner are of reproductive potential
Who cannot join
- 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
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- 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)
- Previous enrolment in the present study
- Participation in a clinical study within 28 days or 5 half-lives of the drug, whichever is longer.
Trial locations and contacts
47 sites in 7 countries.
47 sites in 7 countries
France10 sites
Research Site
Bordeaux, 33076
Research Site
Caen, 14076
Research Site
Clermont-Ferrand, 63011
Research Site
Dijon, 21079
Research Site
Marseille, 13385
Research Site
Nantes, 44202
Research Site
Paris, 75014
Research Site
Pierre Benit Cedex, 69495
Research Site
Toulouse, 31059
Research Site
Villejuif, 94805
United Kingdom9 sites
Research Site
Cambridge, CB2 0QQ
Research Site
Dundee, DD1 9SY
Research Site
Glasgow, G12 0YN
Research Site
Greater London, SW3 6JJ
Research Site
London, NW1 2PG
Research Site
London, SE1 9RY
Research Site
Manchester, M20 4BX
Research Site
Newcastle upon Tyne, NE7 7DN
Research Site
Sutton, SM2 5PT
South Korea8 sites
Research Site
Goyang-si, 10408
Research Site
Seongnam-si, 13620
Research Site
Seoul, 03080
Research Site
Seoul, 03722
Research Site
Seoul, 05505
Research Site
Seoul, 06273
Research Site
Seoul, 06591
Research Site
Seoul, 135-710
United States7 sites
Research Site
Boston, Massachusetts, 02114
Research Site
Detroit, Michigan, 48202
Research Site
Hilliard, Ohio, 43026
Research Site
Newnan, Georgia, 30265
Research Site
Philadelphia, Pennsylvania, 19104
Research Site
St Louis, Missouri, 63110
Research Site
Towson, Maryland, 21204
Netherlands6 sites
Research Site
Amsterdam, 1066 CX
Research Site
Amsterdam, 1081 HV
Research Site
Maastricht, 6229 HX
Research Site
Nijmegen, 6525 GA
Research Site
Rotterdam, 3075 EA
Research Site
Utrecht, 3584 CX
Israel5 sites
Research Site
Haifa, 91096
Research Site
Jerusalem, 91031
Research Site
Petah Tikva, 49100
Research Site
Ramat Gan, 5265601
Research Site
Tel Aviv, 6423906
Switzerland2 sites
Research Site
Chur, CH-7000
Research Site
Lausanne, 1011
About this study
Official title: A Phase I/II Study of MEDI4736 (Anti-PD-L1 Antibody) in Combination With Olaparib (PARP Inhibitor) in Patients With Advanced Solid Tumors
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.
Read the detailed description
This is a phase I/II open-label, multicenter study to evaluate the safety, tolerability, pharmacokinetics (PK) and antitumor activity of MEDI4736 in combination with olaparib in patients with advanced solid tumors, selected based on a rationale for response to olaparib.
Patients will be poly (adenosine diphosphate-ribose) polymerase (PARP)-inhibitor and immunotherapy (IMT)-naïve (defined as no prior exposure to PARP inhibitors or IMT, including, but not limited to, other anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], anti-programmed cell death 1 [PD-1], anti-programmed death-ligand 1 [PD-L1] monoclonal antibodies, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
The 4 initial stage cohorts (Modules 1 to 4) include patients with relapsed small cell lung cancer (SCLC), germline BRCA mutated (gBRCAm) metastatic human epidermal growth factor receptor 2 (HER2)-negative breast cancer, gBRCAm platinum-sensitive relapsed ovarian cancer, and gastric cancer. The data cut-off occurred once all 4 Modules had reached last patient first visit (LPFV) + 2 years and all 4 cohorts had observed a median value for PFS.
Second stage cohorts (Modules 5 to 7) include patients with relapsed gBRCAm platinum-sensitive relapsed ovarian cancer and non gBRCAm platinum-sensitive relapsed ovarian cancer. The final data cut-off will be once Modules 6 and 7 have observed a median value for overall survival. At this timepoint, the clinical study database will close to new data.
- Conditions
- Ovarian, Breast, SCLC, Gastric Cancers
- Being tested
- Olaparib, MEDI4736, Bevacizumab
- Keywords
- MEDIOLA, Olaparib, MEDI4736, Bevacizumab, Ovarian cancer, Breast cancer, Small Cell Lung Cancer, Gastric Cancer, Phase I/II, Adults, PDL-1
- Medical subject headings
- Stomach Neoplasms, Ovarian Neoplasms, Breast Neoplasms, Small Cell Lung Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OlaparibDrug
Olaparib
MEDI4736Drug
MEDI4736
BevacizumabDrug
Also called Avastin
Bevacizumab
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | Includes 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 Receives: Drug: Olaparib; Drug: MEDI4736 |
| Arm 2 | Experimental | Includes 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 Receives: Drug: Olaparib; Drug: MEDI4736 |
| Arm 3 | Experimental | Includes 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 Receives: Drug: Olaparib; Drug: MEDI4736; Drug: Bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: 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.
Measured: 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
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.
Measured: RECIST performed at baseline, and every 8 weeks +/-7 days thereafter. Assessed until 17 Sep 2021.
Initial Stage Cohorts: DCR at Week 28
The DCR at 28 weeks was defined as the percentage of participants who had CR + PR + SD at 28 weeks. Participants demonstrated SD for a minimum interval of 27 weeks (minus 1 week to allow for an early assessment within the assessment window, i.e. 189 days) following the start of treatment. The DCR was determined using Investigator assessments according to RECIST v1.1.
Measured: 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
The DCR at 56 weeks was defined as the percentage of participants who had CR + PR + SD at 56 weeks. Participants demonstrated SD for a minimum interval of 55 weeks (minus 1 week to allow for an early assessment within the assessment window, i.e. 385 days) following the start of treatment. The DCR was determined using Investigator assessments according to RECIST v1.1.
Measured: RECIST performed at baseline, and every 8 weeks +/-7 days thereafter. Assessed until 17 Sep 2021.
Initial and Second Stage Cohorts: 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% CI were calculated using Exact Clopper-Pearson confidence limits for the binomial proportion.
Measured: 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)
The DoR (based on RECIST 1.1 as assessed by the Investigator) was defined as the time from the date of first documented response until date of documented progression or death in the absence of PD. The DoR was calculated using Kaplan-Meier technique.
Measured: 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: Progression-Free Survival (PFS)
The PFS (based on RECIST 1.1 as assessed by the Investigator) was defined as the time from start of study treatment (Day 1; start of olaparib monotherapy for initial stage cohorts) until the date of objective PD or death (by any cause in the absence of disease progression) regardless of whether the patient withdraws from therapy or receives another anticancer therapy prior to disease progression. The PFS was calculated using Kaplan-Meier technique.
Measured: 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 Stage Cohorts: Percentage Change From Baseline in Target Tumor Size at Weeks 12 and 28
The percentage change in target tumor size at each timepoint (based on RECIST 1.1 target lesion measurements) was obtained for each participant taking the difference between the sum of the target lesions at each timepoint and the sum of the target lesions at baseline divided by the sum of the target lesions at baseline times 100. Baseline was defined as the last evaluable assessment prior to starting olaparib treatment.
Measured: Baseline (Day 1) and Weeks 12 and 28. Assessed until DCO 14 Jun 2019
Second Stage Cohorts: Percentage Change From Baseline in Target Tumor Size at Weeks 24 and 56
The percentage change in target tumor size at each timepoint (based on RECIST 1.1 target lesion measurements) was obtained for each participant taking the difference between the sum of the target lesions at each timepoint and the sum of the target lesions at baseline divided by the sum of the target lesions at baseline times 100. Baseline was defined as the last assessment prior to Cycle 1 Day 1.
Measured: Baseline (Day 1) and Weeks 24 and 56. Assessed until DCO 17 Sep 2021
Initial and Second Stage Cohorts: Best Percentage Change From Baseline in Target Tumor Size
The best percentage change from baseline in target tumor size was based on RECIST 1.1 target lesion measurements taken at each RECIST 1.1 assessment. All measurements until PD or the last evaluable assessment in the absence of PD was included in the calculation. Baseline was defined as the last evaluable assessment prior to starting olaparib treatment for initial stage cohorts. Baseline was defined as the last assessment prior to Cycle 1 Day 1 for second stage cohorts.
Measured: From baseline (Day 1) until confirmed PD/death. Assessed until DCO 14 Jun 2019 and 17 Sep 2021 for initial and second stage cohorts, respectively
Initial and Second Stage Cohorts: Time to Study Treatment Discontinuation or Death (TDT)
The TDT was defined as the time from start of study treatment (Day 1; start of olaparib monotherapy for initial stage cohorts) to the earlier of the date of study treatment discontinuation or death. The TDT was calculated using the Kaplan-Meier technique.
Measured: From baseline (Day 1) until treatment discontinuation/death. Assessed until DCO 14 Jun 2019 and 17 Sep 2021 for initial and second stage cohorts, respectively
Initial and Second Stage Cohorts: OS
The OS was defined as the time from the start of study treatment (Day 1; start of olaparib monotherapy for initial stage cohorts) until death due to any cause. The OS was calculated using the Kaplan-Meier technique.
Measured: From baseline (Day 1) until death from any cause. Assessed until DCO 14 Jun 2019 for initial stage cohorts except for ovarian cancer cohort and DCO 17 Sep 2021 for initial stage ovarian cancer cohort and second stage cohorts
Initial and Second Stage Cohorts: Serum Concentrations of MEDI4736
Blood samples were collected to determine the serum concentration of MEDI4736.
Measured: Pre-dose and within 10 minutes of end of infusion on Days 1, 85 and 113; Pre-dose on Days 29, 57 and 169; and 90 days post last dose of MEDI4736. Assessed until DCO 14 Jun 2019 and 17 Sep 2021 for initial and second stage cohorts, respectively
Initial and Second Stage Cohorts: Serum Concentrations of Olaparib
Blood samples were collected to determine the serum concentration of olaparib.
Measured: Pre-dose and 0.5-1 hour postdose on Days 1 and 22 of monotherapy; Pre-dose and 0.5-1, 1-3, 3-6 and 6-12 hours postdose on Day 15 of combination therapy. Assessed until DCO 14 Jun 2019 and 17 Sep 2021 for initial and second stage cohorts, respectively
Second Stage Cohort: Serum Concentrations of Bevacizumab
Blood samples were collected to determine the serum concentration of bevacizumab.
Measured: Pre-dose and within 10 minutes of end of infusion on Days 1 and 85; Pre-dose on Days 29 and 169; and 90 days post last dose of bevacizumab. Assessed until DCO 17 Sep 2021
Initial and Second Stage Cohorts: Number of Participants With Anti-Drug Antibody (ADA) Response to MEDI4736
Blood samples were measured for the presence of ADAs and ADA-neutralizing antibodies (nAb) for MEDI4736 using validated assays. ADA prevalence was defined as the percentage of participants with positive ADA result at any time, baseline or post-baseline. ADA incidence (treatment-emergent ADA) was defined as the sum of both treatment-induced (post-baseline ADA positive only) and treatment-boosted ADA. Treatment-boosted ADA was defined as baseline ADA titer that was boosted to 4-fold or higher following drug administration. Persistently positive was defined as positive at >=2 post-baseline assessments (with >=16 weeks between first and last positive) or positive at last post-baseline assessment. Transiently positive was defined as having at least 1 post-baseline ADA positive assessment and not fulfilling the conditions of persistently positive.
Measured: Pre-dose on Days 1, 15, 57, 85, 113 and 169; and 90 days post-last dose of MEDI4736. Assessed until DCO 14 Jun 2019 and 17 Sep 2021 for initial and second stage cohorts, respectively
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2016 (estimated)
- Study start17 Mar 2016
- Primary completion17 Sep 2021
- Study completion17 Sep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for OvarianStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 264 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- IQVIA Pty Ltd
- Responsible party
- Sponsor
- Investigators
- Susan Domchek, MD, Principal investigator, Abramson Cancer Center, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02734004
- Sponsor's protocol ID
- D081KC00001
- Other IDs
- 2015-004005-16, 2015
- Acronym
- MEDIOLA
- Status last verified
- Jul 2026
- First submitted
- 17 Mar 2016
- Last updated
- 14 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Expanded access
- Available
Publications
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.
PubMed 37939124Staniszewska 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.
PubMed 35756843Domchek 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.
PubMed 32771088
Study at a glance
From the registry record, last updated by the sponsor on 14 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study of MEDI4736 (Anti-PD-L1 Antibody) in Combination With Olaparib (PARP Inhibitor) in Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT02734004
- Acronym / sponsor ID
- MEDIOLA / D081KC00001
- Conditions
- Ovarian, Breast, SCLC, Gastric Cancers
- Keywords
- MEDIOLA, Olaparib, MEDI4736, Bevacizumab, Ovarian cancer, Breast cancer, Small Cell Lung Cancer, Gastric Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 264 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- IQVIA Pty Ltd
- Study start
- 17 Mar 2016 (actual)
- Primary completion
- 17 Sep 2021 (actual)
- Study completion
- 17 Sep 2026 (estimated)
- First posted
- 12 Apr 2016 (estimated)
- Results
- Posted 13 Oct 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a phase I/II open-label, multicenter study to evaluate the safety, tolerability, pharmacokinetics (PK) and antitumor activity of MEDI4736 in combination with olaparib in patients with advanced solid tumors, selected based on a rationale for response to olaparib.
Patients will be poly (adenosine diphosphate-ribose) polymerase (PARP)-inhibitor and immunotherapy (IMT)-naïve (defined as no prior exposure to PARP inhibitors or IMT, including, but not limited to, other anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], anti-programmed cell death 1 [PD-1], anti-programmed death-ligand 1 [PD-L1] monoclonal antibodies, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
The 4 initial stage cohorts (Modules 1 to 4) include patients with relapsed small cell lung cancer (SCLC), germline BRCA mutated (gBRCAm) metastatic human epidermal growth factor receptor 2 (HER2)-negative breast cancer, gBRCAm platinum-sensitive relapsed ovarian cancer, and gastric cancer. The data cut-off occurred once all 4 Modules had reached last patient first visit (LPFV) + 2 years and all 4 cohorts had observed a median value for PFS.
Second stage cohorts (Modules 5 to 7) include patients with relapsed gBRCAm platinum-sensitive relapsed ovarian cancer and non gBRCAm platinum-sensitive relapsed ovarian cancer. The final data cut-off will be once Modules 6 and 7 have observed a median value for overall survival. At this timepoint, the clinical study database will close to new data.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: Olaparib, Drug: MEDI4736Includes 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 | Experimental | Drug: Olaparib, Drug: MEDI4736Includes 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 | Experimental | Drug: Olaparib, Drug: MEDI4736, Drug: BevacizumabIncludes 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 |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Patients must have histologically or cytologically confirmed progressive advanced or metastatic solid tumor of one of the following:
- 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
Key exclusion criteria (17 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OlaparibOlaparib | Drug | Arm 1, Arm 2, Arm 3 |
| MEDI4736MEDI4736 | Drug | Arm 1, Arm 2, Arm 3 |
| BevacizumabAlso: AvastinBevacizumab | Drug | Arm 3 |
Primary outcome
Initial Stage Cohorts: Disease Control Rate (DCR) at Week 12
Time frame: 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.
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).
Second Stage Cohort: Objective Response Rate (ORR)
Time frame: RECIST performed at baseline, and every 8 weeks +/-7 days thereafter. Assessed until 17 Sep 2021.
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.
Second Stage Cohorts: DCR at Week 24
Time frame: RECIST performed at baseline, and every 8 weeks +/-7 days thereafter. Assessed until 17 Sep 2021.
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.
15 secondary outcomes
Second Stage Expansion Cohort: DCR at Week 24
Time frame: RECIST performed at baseline, and every 8 weeks +/-7 days thereafter. Assessed until 17 Sep 2021.
Initial Stage Cohorts: DCR at Week 28
Time frame: 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
Time frame: RECIST performed at baseline, and every 8 weeks +/-7 days thereafter. Assessed until 17 Sep 2021.
Initial and Second Stage Cohorts: ORR
Time frame: 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)
Time frame: 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: Progression-Free Survival (PFS)
Time frame: 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 Stage Cohorts: Percentage Change From Baseline in Target Tumor Size at Weeks 12 and 28
Time frame: Baseline (Day 1) and Weeks 12 and 28. Assessed until DCO 14 Jun 2019
Second Stage Cohorts: Percentage Change From Baseline in Target Tumor Size at Weeks 24 and 56
Time frame: Baseline (Day 1) and Weeks 24 and 56. Assessed until DCO 17 Sep 2021
Initial and Second Stage Cohorts: Best Percentage Change From Baseline in Target Tumor Size
Time frame: From baseline (Day 1) until confirmed PD/death. Assessed until DCO 14 Jun 2019 and 17 Sep 2021 for initial and second stage cohorts, respectively
Initial and Second Stage Cohorts: Time to Study Treatment Discontinuation or Death (TDT)
Time frame: From baseline (Day 1) until treatment discontinuation/death. Assessed until DCO 14 Jun 2019 and 17 Sep 2021 for initial and second stage cohorts, respectively
Initial and Second Stage Cohorts: OS
Time frame: From baseline (Day 1) until death from any cause. Assessed until DCO 14 Jun 2019 for initial stage cohorts except for ovarian cancer cohort and DCO 17 Sep 2021 for initial stage ovarian cancer cohort and second stage cohorts
Initial and Second Stage Cohorts: Serum Concentrations of MEDI4736
Time frame: Pre-dose and within 10 minutes of end of infusion on Days 1, 85 and 113; Pre-dose on Days 29, 57 and 169; and 90 days post last dose of MEDI4736. Assessed until DCO 14 Jun 2019 and 17 Sep 2021 for initial and second stage cohorts, respectively
Initial and Second Stage Cohorts: Serum Concentrations of Olaparib
Time frame: Pre-dose and 0.5-1 hour postdose on Days 1 and 22 of monotherapy; Pre-dose and 0.5-1, 1-3, 3-6 and 6-12 hours postdose on Day 15 of combination therapy. Assessed until DCO 14 Jun 2019 and 17 Sep 2021 for initial and second stage cohorts, respectively
Second Stage Cohort: Serum Concentrations of Bevacizumab
Time frame: Pre-dose and within 10 minutes of end of infusion on Days 1 and 85; Pre-dose on Days 29 and 169; and 90 days post last dose of bevacizumab. Assessed until DCO 17 Sep 2021
Initial and Second Stage Cohorts: Number of Participants With Anti-Drug Antibody (ADA) Response to MEDI4736
Time frame: Pre-dose on Days 1, 15, 57, 85, 113 and 169; and 90 days post-last dose of MEDI4736. Assessed until DCO 14 Jun 2019 and 17 Sep 2021 for initial and second stage cohorts, respectively
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jul 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37939124Drew 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.
- Derived from this study: PubMed 35756843Staniszewska 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.
- Derived from this study: PubMed 32771088Domchek 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.
- Related InfoLink provided by the sponsor.
- Related InfoLink provided by the sponsor.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Susan Domchek, MD principal investigator
Abramson Cancer Center, University of Pennsylvania
47 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Olaparib, MEDI4736 and Bevacizumab in people with Ovarian and Breast, run by AstraZeneca at 47 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 14 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 47 sites in France, United Kingdom, South Korea, United States, Netherlands and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Oct 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Initial Stage Cohorts: Disease Control Rate (DCR) at Week 12 (time frame: 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.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02734004, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jul 2026.