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NCT Number: NCT03737643

Durvalumab Treatment in Combination With Chemotherapy and Bevacizumab, Followed by Maintenance Durvalumab, Bevacizumab and Olaparib Treatment in Advanced Ovarian Cancer Patients

This is a Phase III randomised, double-blind, multi-centre study to evaluate the efficacy and safety of durvalumab in combination with standard of care platinum based chemotherapy and bevacizumab followed by maintenance durvalumab and bevacizumab or durvalumab, bevacizumab and olaparib in patients with newly diagnosed advanced ovarian cancer.

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This study is active but is not currently recruiting participants.

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Key information

Conditions

Advanced Ovarian Cancer Adnexal Diseases Endocrine Gland Neoplasms Endocrine System Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Genital Diseases Genital Diseases, Female Genital Neoplasms, Female Gonadal Disorders Neoplasms Neoplasms by Site Ovarian Diseases Ovarian Neoplasms Urogenital Diseases Urogenital Neoplasms

Age range

18 year–130 year

Sex eligibility

Female

Study type

Interventional

Phase

Phase 3

Primary location

Research Site, Graz, Austria

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About this study

Eligible patients will be those patients with newly diagnosed, histologically confirmed advanced (Fédération Internationale de Gynécologie et d'Obstétrique [FIGO] Stage III-IV) ovarian, primary peritoneal cancer and/or fallopian-tube cancer. All patients should be candidates for cytoreductive surgery which could be conducted as immediate upfront primary surgery following diagnosis or can be conducted after initiation of platinum based neoadjuvant chemotherapy. All patients should be eligible to start first line platinum based chemotherapy in combination with bevacizumab.

The study aims to evaluate the efficacy and safety of standard of care (SoC) platinum-based chemotherapy and bevacizumab followed by maintenance bevacizumab either as monotherapy, or in combination with durvalumab, or in combination with durvalumab and olaparib. Therefore, this study aims to see which combination allows patients to live longer without the cancer coming back or getting worse. The study is also looking to see which combination makes patients live longer and how the treatment and the cancer affects their quality of life.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key Inclusion Criteria:

Female patients with newly diagnosed, histologically confirmed, advanced (Stage III-IV) high grade epithelial ovarian cancer including high grade serious, high grade endometriod, clear cell ovarian cancer or carcinosarcoma, primary peritoneal cancer and / or fallopian-tube cancer

  • Patients must be aged ≥18 years of age. For patients enrolled in Japan that are aged <20 year
  • All patients should be candidates for cytoreductive surgery either: upfront primary surgery OR plan to undergo chemotherapy with interval debulking surgery
  • Evidence of presence or absence of BRCA1/2 mutation in tumour tissue
  • Mandatory provision of tumour sample for centralised tBRCA testing
  • ECOG performance status 0-1
  • Patients must have preserved organ and bone marrow function
  • Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test

Key Exclusion Criteria:

Non-epithelial ovarian cancer, borderline tumors, low grade epithelial tumors or mucinous histology

  • Prior systemic anti-cancer therapy for ovarian cancer
  • Inability to determine the presence or absence of a deleterious or suspected deleterious BRCA mutation
  • Prior treatment with PARP inhibitor or immune mediated therapy
  • Planned intraperitoneal cytotoxic chemotherapy
  • Active or prior documented autoimmune or inflammatory disorders
  • Patients considered a poor medical risk due to a serious, uncontrolled intercurrent illness
  • Clinically significant cardiovascular disease
  • Patients with known brain metastases
  • History of another primary malignancy except for:
  • Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of study treatment and of low potential risk for recurrence (patients who have received prior adjuvant chemotherapy for early stage breast cancer may be eligible, provided that it was completed ≥3 years prior to registration, and that the patient remains free of recurrent or metastatic disease)
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
  • Adequately treated carcinoma in situ without evidence of disease
  • Endometrial cancer FIGO Stage IA, Grade 1 or Grade 2
  • Persistent toxicities CTCAE Grade >2 caused by previous cancer therapy
  • Patients with a known hypersensitivity to olaparib, durvalumab or any of the excipients of these products and to the combination/comparator agents
  • Breast feeding women

Treatment and study plan

Bevacizumab

Drug

Bevacizumab by intravenous infusion. In tBRCAm cohort bevacizumab is optional according to local practice.

Durvalumab

Drug

Durvalumab by intravenous infusion

Olaparib

Drug

Olaparib tablets

Placebo olaparib

Drug

Placebo tablets to match olaparib

durvalumab placebo

Drug

Matching placebo for intravenous infusion

Carboplatin+Paclitaxel

Drug

Standard of care chemotherapy

Primary outcomes

  1. Progression-free Survival (PFS) by Investigator Assessment Using Modified RECIST 1.1 - Full Analysis Set

    Time frame: At baseline, within 3 weeks of last dose of chemotherapy, then every 12 weeks for 3 years and thereafter every 24 weeks. Assessed until primary analysis - (05DEC2022 for Global cohort, 17MAR2025 for China cohort) - upto 46 months

    To determine the efficacy of durvalumab in combination with platinum based chemotherapy and bevacizumab and continued as maintenance in combination with bevacizumab and olaparib versus SoC platinum based chemotherapy in combination with bevacizumab by assessment of PFS (using investigator assessment according to Response Evaluation Criteria in Solid Tumours version 1.1 [RECIST 1.1]) in the first line treatment of patients with newly diagnosed advanced ovarian cancer.

    Per MTP, the comparison of SoC+D+O v SoC in the Non-tbRCAm patients is a primary endpoint. SoC+D v SoC is reported separately as a secondary endpoint. Results for tBRCAm SoC+D+O are not presented as this was prespecified to be assessed only in the Non-tBRCAm patients.

  2. Progression-free Survival (PFS) by Investigator Assessment Using Modified RECIST 1.1 - (Full Analysis Set, HRD Positive)

    Time frame: At baseline, within 3 weeks of last dose of chemotherapy, then every 12 weeks for 3 years and thereafter every 24 weeks. Assessed until DCO1 - (05DEC2022 for Global cohort, 17MAR2025 for China cohort) - upto 46 months

    To determine the efficacy of durvalumab and olaparib assessed by PFS in the first line treatment of patients with newly diagnosed advanced ovarian cancer.

    Per MTP, the comparison of SoC+D+O v SoC in the Non-tBRCAm HRD positve population is a primary endpoint. SoC+D v SoC is reported separately as a secondary endpoint. Results for tBRCAm SoC+D+O are not presented as as this was prespecified to be assessed only in the Non-tBRCAm patients.

Secondary outcomes

  1. Progression-free Survival (PFS) by Investigator Assessment Using Modified RECIST 1.1 - Full Analysis Set

    Time frame: At baseline, within 3 weeks of last dose of chemotherapy, then every 12 weeks for 3 years and thereafter every 24 weeks. For global cohort, assessed until DCO2 (18SEP2023) - up to 55 months. For China cohort assessed until DCO1 (17MAR2025) - 46 months.

    To determine the efficacy of durvalumab assessed by PFS in the first line treatment of patients with newly diagnosed advanced ovarian cancer.

    Per MTP, the comparison of SoC+D v SoC is a secondary endpoint. SoC+D+O v SoC is reported separately as a primary endpoint. Results for tBRCAm SoC+D+O are not presented as this was prespecified to be assessed only in the Non-tBRCAm patients.

  2. Overall Survival - Full Analysis Set

    Time frame: Survival assessed every 12 weeks after RECIST 1.1 defined progression. For global cohort, assessed until DCO3 (17MAR2025) - up to 73 months. For China cohort assessed until DCO1 (17MAR2025) - up to 46 months.

    To determine the efficacy of durvalumab and olaparib assessed by OS in the first line treatment patients with newly diagnosed advanced ovarian cancer.

    Overall survival (OS) is defined as the time from randomisation/allocation to death due to any cause regardless of whether the patient withdraws from randomised therapy or receives another anti-cancer therapy.

    Results for tBRCAm SoC+D+O are not presented as this was prespecified to be assessed only in the Non-tBRCAm patients.

  3. Overall Survival - (Full Analysis Set, HRD-positive)

    Time frame: Survival assessed every 12 weeks after RECIST 1.1 defined progression. For global cohort, assessed until DCO3 (17MAR2025) - up to 73 months. For China cohort assessed until DCO1 (17MAR2025) - up to 46 months.

    To determine the efficacy of durvalumab and olaparib assessed by OS in the first line treatment patients with newly diagnosed advanced ovarian cancer.

    Overall survival (OS) is defined as the time from randomisation/allocation to death due to any cause regardless of whether the patient withdraws from randomised therapy or receives another anti-cancer therapy.

    Results for tBRCAm SoC+D+O are not presented as this was prespecified to be assessed only in the Non-tBRCAm patients.

  4. Time to Second Progression or Death Based on Local Standard Clinical Practice (PFS2) - Full Analysis Set

    Time frame: Assessed every 12 weeks after RECIST 1.1 defined progression. For global cohort, assessed until DCO3 (17MAR2025) - up to 73 months. For China cohort assessed until DCO1 (17MAR2025) - 46 months.

    To assess the efficacy of durvalumab and olaparib in terms of PFS2 in the first line treatment of patients with newly diagnosed advanced ovarian cancer.

    Time to second progression or death (PFS2) is defined as the time from the date of randomisation/allocation to the earliest of the progression event subsequent to first subsequent therapy or death.

    Results for tBRCAm SoC+D+O are not presented as this was prespecified to be assessed only in the Non-tBRCAm patients.

  5. Time to Second Progression or Death Based on Local Standard Clinical Practice (PFS2) - (Full Analysis Set, HRD-positive)

    Time frame: Assessed every 12 weeks after RECIST 1.1 defined progression. For global cohort, assessed until DCO3 (17MAR2025) - up to 73 months. For China cohort assessed until DCO1 (17MAR2025) - 46 months.

    To assess the efficacy of durvalumab and olaparib in terms of PFS2 in the first line treatment of patients with newly diagnosed advanced ovarian cancer.

    Time to second progression or death (PFS2) is defined as the time from the date of randomisation/allocation to the earliest of the progression event subsequent to first subsequent therapy or death.

    Results for tBRCAm SoC+D+O are not presented as this was prespecified to be assessed only in the Non-tBRCAm patients.

  6. Objective Response Rate Based on Investigator Assessment (Full Analysis Set)

    Time frame: At baseline, within 3 weeks of last dose of chemotherapy, then every 12 weeks for 3 years and thereafter every 24 weeks. Up to 55 months for global non-tBRCAm (DCO2 18SEP2023). Up to 46 for Global tBRCAm (DCO1 05DEC2022) and China (DCO1 17MAR2025)

    To assess the efficacy of durvalumab and olaparib in terms of ORR (Complete Response + Partial Response) by investigator assessment by modified RECIST 1.1:

    • in all patients with evaluable disease at baseline
    • prior to surgery in those patients planned to have IDS with evaluable disease at baseline.

    Objective response rate (ORR) is defined similarly for the non-tBRCAm and tBRCAm cohorts as the number (percentage) of patients with at least one investigator-assessed visit response of CR or PR and will be based on a subset of all randomised/allocated patients who have evaluable disease at baseline per the site investigator.

  7. Objective Response Rate Based on Investigator Assessment (Full Analysis Set, HRD-positive)

    Time frame: At baseline, within 3 weeks of last dose of chemotherapy, then every 12 weeks for 3 years and thereafter every 24 weeks. Up to 55 months for global non-tBRCAm (DCO2 18SEP2023). Up to 46 for China (DCO1 17MAR2025)

    To assess the efficacy of durvalumab and olaparib in terms of ORR (Complete Response + Partial Response) by investigator assessment by modified RECIST 1.1

    • in all patients with evaluable disease at baseline
    • prior to surgery in those patients planned to have IDS with evaluable disease at baseline.

    Objective response rate (ORR) is defined similarly for the non-tBRCAm and tBRCAm cohorts as the number (percentage) of patients with at least one investigator-assessed visit response of CR or PR and will be based on a subset of all randomised/allocated patients who have evaluable disease at baseline per the site investigator.

    This was prespecified to be assessed only in the non-tBRCAm cohort.

  8. Duration of Objective Response Based on Investigator Assessments (Full Analysis Set)

    Time frame: At baseline, within 3 weeks of last dose of chemotherapy, then every 12 weeks for 3 years and thereafter every 24 weeks. Up to 55 months for global non-tBRCAm (DCO2 18SEP2023). Up to 46 for Global tBRCAm (DCO1 05DEC2022)

    To assess the efficacy of durvalumab and olaparib in terms of duration of response (DoR) in the first line treatment of patients with newly diagnosed advanced ovarian cancer.

    Duration of response (DoR) is defined similarly for the non-tBRCAm and tBRCAm cohorts using the corresponding FAS among patients with a response (CR or PR), as the time from the date of first documented response (i.e., the first time at which the visit response is PR or CR) according to modified RECIST v1.1 as assessed by the investigator until date of documented progression or death in the absence of disease progression.

    This was prespecified to be assessed only in the Global patients.

  9. Duration of Objective Response Based on Investigator Assessments (Full Analysis Set, HRD-positive)

    Time frame: At baseline, within 3 weeks of last dose of chemotherapy, then every 12 weeks for 3 years and thereafter every 24 weeks. Up to 55 months for global non-tBRCAm (DCO2 18SEP2023).

    To assess the efficacy of durvalumab and olaparib in terms of duration of response (DoR) in the first line treatment of patients with newly diagnosed advanced ovarian cancer.

    Duration of response (DoR) is defined similarly for the non-tBRCAm and tBRCAm cohorts using the corresponding FAS among patients with a response (CR or PR), as the time from the date of first documented response (i.e., the first time at which the visit response is PR or CR) according to modified RECIST v1.1 as assessed by the investigator until date of documented progression or death in the absence of disease progression.

    This was prespecified to be assessed only in Global Non-tBRCAm patients.

  10. Time to First Subsequent Therapy (TFST) - Full Analysis Set

    Time frame: Assessed every 12 weeks following treatment discontinuation. For global cohort, assessed until DCO3 (17MAR2025) - up to 73 months. For China cohort assessed until DCO1 (17MAR2025) - up to 46 months.

    To assess the efficacy of durvalumab and olaparib in terms of TFST in the first line treatment of patients with newly diagnosed advanced ovarian cancer.

    Time to start of first subsequent therapy or death (TFST) is defined as the time from randomisation/allocation to the earlier of first subsequent therapy start date following study treatment discontinuation, or death.

    This was prespecified to be assessed only in Non-tBRCAm patients.

  11. Time to First Subsequent Therapy (TFST) - (Full Analysis Set, HRD-positive)

    Time frame: Assessed every 12 weeks following treatment discontinuation. For global cohort, assessed until DCO3 (17MAR2025) - up to 73 months. For China cohort assessed until DCO1 (17MAR2025) - up to 46 months.

    To assess the efficacy of durvalumab and olaparib in terms of TFST in the first line treatment of patients with newly diagnosed advanced ovarian cancer.

    Time to start of first subsequent therapy or death (TFST) is defined as the time from randomisation/allocation to the earlier of first subsequent therapy start date following study treatment discontinuation, or death.

    This was prespecified to be assessed only in Non-tBRCAm patients.

  12. Time to Second Subsequent Therapy (TSST) - Full Analysis Set

    Time frame: Assessed every 12 weeks following treatment discontinuation. For global cohort, assessed until DCO3 (17MAR2025) - up to 73 months. For China cohort assessed until DCO1 (17MAR2025) - up to 46 months.

    To assess the efficacy of durvalumab and olaparib in terms of TSST in the first line treatment of patients with newly diagnosed advanced ovarian cancer.

    Time to second subsequent therapy or death (TSST) is defined as the time from randomisation/allocation to the earlier of the second subsequent anti-cancer therapy start date following study treatment discontinuation, or death.

    This was prespecified to be assessed only in Non-tBRCAm patients.

  13. Time to Second Subsequent Therapy (TSST) - (Full Analysis Set, HRD-positive)

    Time frame: Assessed every 12 weeks following treatment discontinuation. For global cohort, assessed until DCO3 (17MAR2025) - up to 73 months. For China cohort assessed until DCO1 (17MAR2025) - up to 46 months.

    To assess the efficacy of durvalumab and olaparib in terms of TSST in the first line treatment of patients with newly diagnosed advanced ovarian cancer.

    Time to second subsequent therapy or death (TSST) is defined as the time from randomisation to the earlier of the second subsequent anti-cancer therapy start date following study treatment discontinuation, or death.

    This was prespecified to be assessed only in Non-tBRCAm patients.

  14. Time to Treatment Discontinuation (TDT) - Full Analysis Set

    Time frame: Assessed through study completion, up to 73 months for global non-tBRCAm (DCO3 17MAR2025) and up to 46 months for and China (DCO1 17MAR2025)

    To assess the efficacy of durvalumab and olaparib in terms of TDT in the first line treatment of patients with newly diagnosed advanced ovarian cancer.

    Time to permanent study treatment discontinuation or death (TDT) is defined as the time from randomisation/allocation to the earlier of the date of permanent study treatment discontinuation or death.

    This was prespecified to be assessed only in Non-tBRCAm patients.

  15. Time to Treatment Discontinuation (TDT) - (Full Analysis Set, HRD-positive)

    Time frame: Assessed through study completion, up to 73 months for global non-tBRCAm (DCO3 17MAR2025) and up to 46 months for and China (DCO1 17MAR2025)

    To assess the efficacy of durvalumab and olaparib in terms of TDT in the first line treatment of patients with newly diagnosed advanced ovarian cancer.

    Time to permanent study treatment discontinuation or death (TDT) is defined as the time from randomisation/allocation to the earlier of the date of permanent study treatment discontinuation or death.

    This was prespecified to be assessed only in Non-tBRCAm patients.

  16. Change From Baseline in Physical Function Score of the EORTC-QLQ-C30 and EORTC-QLQ-OV28 Questionnaires - Full Analysis Set

    Time frame: Assessed at week 96.

    To determine the effects on HRQoL, global health status and ovarian cancer symptoms of the combination of durvalumab and olaparib in the first line treatment of non-tBRCAm patients with newly diagnosed advanced ovarian cancer. The physical functioning score is a score from 0 to 100. Higher scores on the physical functioning score indicate better health status/function.

    This was prespecified to be assessed only in Global Non-tBRCAm patients.

  17. Change From Baseline in Physical Function Score of the EORTC-QLQ-C30 and EORTC-QLQ-OV28 Questionnaires - (Full Analysis Set, HRD Positive)

    Time frame: Assessed at week 96.

    To determine the effects on HRQoL, global health status and ovarian cancer symptoms of the combination of durvalumab and olaparib in the first line treatment of non-tBRCAm patients with newly diagnosed advanced ovarian cancer. The physical functioning score is a score from 0 to 100. Higher scores on the physical functioning score indicate better health status/function.

    This was prespecified to be assessed only in Global Non-tBRCAm patients.

  18. Change From Baseline in Global Health Status/QoL Score of the EORTC-QLQ-C30 and EORTC-QLQ-OV28 Questionnaires - Full Analysis Set

    Time frame: Assessed at week 96.

    To determine the effects on HRQoL, global health status and ovarian cancer symptoms of the combination of durvalumab and olaparib in the first line treatment of non-tBRCAm patients with newly diagnosed advanced ovarian cancer. The global health status/quality of life (QoL) is a score from 0 to 100. Higher scores on the global health status/QoL indicate better health status/function.

    This was prespecified to be assessed only in Global Non-tBRCAm patients.

  19. Change From Baseline in Global Health Status/QoL Score of the EORTC-QLQ-C30 and EORTC-QLQ-OV28 Questionnaires - (Full Analysis Set, HRD Positive)

    Time frame: Assessed at week 96

    To determine the effects on HRQoL, global health status and ovarian cancer symptoms of the combination of durvalumab and olaparib in the first line treatment of non-tBRCAm patients with newly diagnosed advanced ovarian cancer. The global health status/quality of life (QoL) is a score from 0 to 100. Higher scores on the global health status/QoL indicate better health status/function.

    This was prespecified to be assessed only in Global Non-tBRCAm patients.

  20. Summary of Serum Concentrations (μg/mL) of Durvalumab for Each Treatment - Non-tBRCAm Cohort With Primary Cytoreductive Surgery (Pharmacokinetic Analysis Set)

    Time frame: Assessed at Day 85 pre-dose, Day 183 pre-dose and 3 months after last dose of durvalumab.

    To characterize the PK of durvalumab in combination with bevacizumab and olaparib.

    This was prespecified to be assessed only in Global Non-tBRCAm patients.

  21. Summary of Plasma Concentrations (μg/mL) of Olaparib - Non-tBRCAm Cohort With Primary Cytoreductive Surgery (Pharmacokinetic Analysis Set)

    Time frame: Assessed on Day 148 post-dose (1-3 hours, 3-6 hours and 6-12 hours)

    To determine olaparib plasma concentrations via sparse sampling for population PK analyses.

    This was prespecified to be assessed only in Global Non-tBRCAm patients.

  22. Summary of ADA Responses During the Study for Durvalumab - Non-tBRCAm Cohort With Primary Cytoreductive Surgery (ADA Analysis Set)

    Time frame: Assessed pre-infusion at Cycle 2, Cycle 4, Cycle 6 and the third cycle of the maintenance phase as well as 3 months after last dose of durvalumab

    To characterize the immunogenicity of durvalumab in combination with bevacizumab and olaparib.

    This was prespecified to be assessed only in Global Non-tBRCAm patients.

Sponsors and collaborators

Lead sponsor

AstraZeneca

Industry

Collaborators

  • European Network of Gynaecological Oncological Trial Groups (ENGOT)
  • GOG Foundation
  • Myriad Genetic Laboratories, Inc.

Registry information

Official study title

A Phase III Randomised, Double-Blind, Placebo-Controlled, Multicentre Study of Durvalumab in Combination With Chemotherapy and Bevacizumab, Followed by Maintenance Durvalumab, Bevacizumab and Olaparib in Newly Diagnosed Advanced Ovarian Cancer Patients (DUO-O).

Acronym: DUO-O

Important dates

Study start
2019
Primary completion
2025
Study completion
2026
First posted
Nov 9, 2018
Registry last updated
Jul 7, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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