This is a phase III randomised, double-blind, placebo-controlled, multicentre, global study to assess the effectiveness and safety of standard of care (SoC) platinum-based chemotherapy and bevacizumab followed by maintenance therapy of bevacizumab either alone, or in combination with durvalumab, or in combination with durvalumab and olaparib in patients newly diagnosed with advanced ovarian cancer.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

18 Feb 2019 → 20 Apr 2026

Decision date (initial)

2024-10-07

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB

External identifiers

EU CT number

2022-502747-35-00

EudraCT number

2017-004632-11

ClinicalTrials.gov

NCT03737643

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To determine the efficacy of durvalumab and olaparib assessed by PFS in the first line treatment of non-tBRCAm HRD positive patients and all non-tBRCAm patients with newly diagnosed advanced ovarian cancer.

Secondary objectives 8

1. PFS in non-tBRCAm cohort
2. OS in non-tBRCAm HRD positive and all non-tBRCAm cohort
3. ORR, ORR pre-surgery in IDS group, duration of response, PFS2, TFST, TSST and TDT in non-tBRCAm cohort
4. Health-related Quality of Life Outcomes (HRQoL), global health status and ovarian cancer symptoms in non-tBRCAm cohort
5. pCR in patients undergoing IDS in non-tBRCAm cohort
6. PK and Ig of durvalumab in sampling of population
7. PK of olaparib in sampling of population
8. The potential additional clinical benefit in tBRCAm cohort (PFS, PFS2, ORR, ORR pre-surgery in IDS group, duration of response, TFST, TSST, TDT, HRQoL, proportion of patients with pCR in patients undergoing IDS)

Conditions and MedDRA coding

Newly diagnosed advanced (FIGO stage III-IV) high grade epithelial ovarian, fallopian or primary peritoneal cancer

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared. AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment https://vivli.org/. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Female patients with newly diagnosed, histologically confirmed, advanced (Stage III-IV) high grade epithelial ovarian cancer including high grade serous, high grade endometriod, clear cell ovarian cancer or carcinosarcoma, primary peritoneal cancer and / or fallopian-tube cancer
2. Patients must be aged ≥18 years of age
3. All patients should be candidates for cytoreductive surgery either: upfront primary surgery OR plan to undergo chemotherapy with interval debulking surgery
4. Mandatory provision of tumour sample for centralised tBRCA testing
5. Evidence of presence or absence of BRCA1/2 mutation in tumour tissue
6. ECOG performance status 0-1
7. Patients must have preserved organ and bone marrow function
8. Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test

Exclusion criteria 8

1. Non-epithelial ovarian cancer, borderline tumors, low grade epithelial tumors or mucinous histology
2. Prior systemic anti-cancer therapy for ovarian cancer
3. Prior treatment with PARP inhibitor or immune mediated therapy
4. Planned intraperitoneal cytotoxic chemotherapy
5. Active or prior documented autoimmune or inflammatory disorders
6. Patients considered a poor medical risk due to a serious, uncontrolled intercurrent illness
7. Clinically significant cardiovascular disease
8. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression Free Survival (PFS) is defined as the time from randomisation to the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from assigned therapy or receives another anticancer therapy prior to progression.

Secondary endpoints 11

1. Progression Free Survival (PFS)
2. Overall Survival (OS)
3. Second Progression (PFS2)
4. Objective Response Rate (ORR)
5. Duration of response (DoR)
6. Time to first subsequent therapy (TFST)
7. Time to second subsequent therapy (TSST)
8. Time to discontinuation or death (TDT)
9. Pathological complete response (pCR)
10. Health related Quality of Life (HRQoL)
11. Pharmacokinetic and Immunogenicity

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Placebo 2

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

Astraallen Gartuna, Karlebyhus Byggnad 674 Karlebyhus Byggnad 674

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

Global Clinical Lead

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Locations

12 EU/EEA countries · 97 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 52 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications