A Study to Evaluate the Use of Durvalumab in Combination With Platinum-based Chemotherapy Followed by Durvalumab With Olaparib as First-line Treatment in Advanced or Recurrent Endometrial Cancer in Spain

Phase 3

Recruiting

• Conditions: Advanced or Recurrent Endometrial Cancer
• Interventions: Drug: Durvalumab + Chemotherapy phase; Drug: Durvalumab + Olaparib phase

• Registration Number: NCT06746116
• Lead Sponsor: AstraZeneca

Brief Summary

This is a phase IIIb, interventional, single arm, multicentre study assessing the safety profile of durvalumab in combination with carboplatin-paclitaxel chemotherapy followed by durvalumab with olaparib as first-line treatment for patients with pMMR aEC as the primary endpoint.

The study will include approximately 85 patients distributed in approximately 20 sites in Spain.

The planned duration of patient recruitment is approximately 12 months. Each patient will be followed up from screening for 36 months, until end of study period, death, withdrawal from study or loss to follow-up; whichever occurs first.

Enrolment will be opened to all eligible patients treated with durvalumab in combination with carboplatin-paclitaxel chemotherapy followed by durvalumab with olaparib as first-line treatment for patients with pMMR aEC. In addition, adequate tumour tissue before study entry, stool and blood sample collected will be required for central analysis to monitor the status of relevant biomarkers.

Detailed Description

The purpose of this study is to describe the safety profile of durvalumab in combination with platinum-based chemotherapy followed by durvalumab with olaparib as first-line treatment for patients with pMMR advanced or recurrent endometrial cancer.

Study population: Approximately 85 eligible patients with newly diagnosed pMMR advanced or recurrent endometrial cancer (aEC) will be enrolled into the study distributed in approximately 20 sites in Spain.

Study details include:

* The recruitment period will be approximately 12 months.

* The study duration will be approximately 48 months (12 months recruitment period + 36 months treatment and follow-up).

* The median treatment duration will be approximately 13 months based on treatment duration for durvalumab + olaparib in DUO-E (22) (until objective radiological disease progression, unacceptable toxicity, consent withdrawal or death). Those patients in complete response will be allowed to discontinue durvalumab plus olaparib after completing 2 years in the maintenance phase.

* The analysis for the primary objective is planned to be conducted 12 months after LSI to allow all patients have had the opportunity for 12 months of follow up, and at the end of the follow-up of the last patient up to 36 months.

* The visit frequency will be:

oChemotherapy Phase: every 21 days (every cycle). oMaintenance Phase: every 28 days (every cycle)

Treatment:

* Durvalumab + Chemotherapy phase: Durvalumab (IV) with SoC (carboplatin + paclitaxel chemotherapy: patients should receive at least 4, but preferably 6 cycles) every three weeks.

* Durvalumab + Olaparib phase: durvalumab (IV) with olaparib (tablets) every four weeks until progression.

Study Timeline

• Study First Submitted: 2024-11-28
• Study First Submitted QC: 2024-12-17
• Study First Posted: 2024-12-24
• Study Start: 2024-12-30
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-06
• Last Update Posted: 2025-05-07
• Primary Completion: 2028-11-30
• Study Completion: 2028-11-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 85

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Single Arm	Durvalumab + Chemotherapy phase	Durvalumab + Chemotherapy (chemotherapy phase) plus Durvalumab + Olaparib (maintenence phase)
Single Arm	Durvalumab + Olaparib phase	Durvalumab + Chemotherapy (chemotherapy phase) plus Durvalumab + Olaparib (maintenence phase)

Primary Outcome Measures

Name	Time	Method
Number of patients with Adverse Events	Time from enrollment up to at least 90 days after last dose of study treatment	Safety and tolerability will be evaluated in terms of Adverse Events (AEs), Serious AEs (SAEs), and immune-mediated AEs (imAEs)

Secondary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS)	From date of enrollment through to disease progression, death, withdrawn from study, or end of study (approximately 48 months)	Defined as the time from the date of first dose of treatment until the date of objective disease progression or death (by any cause in the absence of progression). The measure of interest is the median PFS.
Objective Response Rate (ORR)	From date of enrollment through to disease progression, death, withdrawn from study, or end of study (approximately 48 months)	Defined as the percentage of patients with a confirmed investigator-assessed response of CR or PR and will be based on a subset of all included patients with measurable disease at baseline per the site investigator.
Duration of Response (DoR)	From date of enrollment through to disease progression, death, withdrawn from study, or end of study (approximately 48 months)	Defined as the time from the date of first documented response (which is subsequently confirmed) until date of documented progression or death in the absence of disease progression.
Overall Survival (OS)	From date of enrollment through to disease progression, death, withdrawn from study, or end of study (approximately 48 months)	Defined as the time from the date of first dose of treatment2 until death from any cause.
Change in EORTC QLQ-C30 score	From date of enrollment through to disease progression, death, withdrawn from study, or end of study (approximately 48 months)	Change from baseline (enrollment) in EORTC QLQ-C30 score every 12 weeks until end of treatment or disease progression.
Change in EORTC QLQ-EN24 score	From date of enrollment through to disease progression, death, withdrawn from study, or end of study (approximately 48 months)	Change from baseline (enrollment) in EORTC QLQ-EN24 score every 12 weeks until end of treatment or disease progression.
Clinically meaningful deterioration	From date of enrollment through to disease progression, death, withdrawn from study, or end of study (approximately 48 months)	Percentage of patients having absolute change in EORTC-QLQ-C30 and EORTC-QLQ-EN24 score from baseline of ≥10 at 6, 12, 24 and 36 months after LSI.

Trial Locations

Locations (1)

Research Site; 🇪🇸 Zaragoza, Spain