Durvalumab With or Without Olaparib as Maintenance Therapy After First-Line Treatment of Advanced and Recurrent Endometrial Cancer

Phase 3Active Not RecruitingNCT04269200

AstraZeneca805 enrolled

Overview

A study to assess the efficacy and safety of durvalumab in combination with platinum-based chemotherapy (paclitaxel + carboplatin) followed by maintenance durvalumab with or without olaparib for patients with newly diagnosed advanced or recurrent endometrial cancer.

This Phase III study will assess the efficacy and safety of durvalumab in combination with platinum-based chemotherapy (paclitaxel + carboplatin) followed by maintenance durvalumab with or without olaparib for patients with newly diagnosed advanced or recurrent endometrial cancer. Target patient population: Adult female patients with histologically confirmed diagnosis of epithelial endometrial carcinoma (excluding sarcomas): newly diagnosed Stage III, newly diagnosed Stage IV, or recurrent endometrial cancer

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

805

Conditions

Endometrial Neoplasms

Interventions

olaparibDRUG

Olaparib tablets

durvalumabBIOLOGICAL

Durvalumab by intravenous infusion

durvalumab placeboDRUG

Matching placebo for intravenous infusion

olaparib placebo

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 150 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age ≥18 years at the time of screening and female. * Histologically confirmed diagnosis of epithelial endometrial carcinoma. All histologies, including carcinosarcomas, will be allowed. Sarcomas will not be allowed. * Patient must have endometrial cancer in one of the following categories: 1. Newly diagnosed Stage III disease (measurable disease per RECIST 1.1 following surgery or diagnostic biopsy), 2. Newly diagnosed Stage IV disease (with or without disease following surgery or diagnostic biopsy) 3. Recurrence of disease (measurable or non-measurable disease per RECIST 1.1) where the potential for cure by surgery alone or in combination is poor. * Naïve to first line systemic anti-cancer treatment. For patients with recurrent disease only, prior systemic anti-cancer treatment is allowed only if it was administered in the adjuvant setting and there is at least 12 months from date of last dose of systemic anti-cancer treatment administered to date of subsequent relapse * FPPE tumor sample must be available for MMR evaluation. * Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days of starting study treatment. Exclusion Criteria: * History of leptomeningeal carcinomatosis. * Brain metastases or spinal cord compression. * Prior treatment with PARP inhibitors. * Any prior exposure to immune-mediated therapy, including (but not limited to) other anti CTLA-4, anti-PD-1, anti-PD-L1, or anti-programmed-cell-death ligand 2 (anti-PD-L2) antibodies, excluding therapeutic anticancer vaccines.

Locations (201)

Outcomes

Primary Outcomes

Progression-free Survival (PFS) According to RECIST 1.1, Based on Investigator Assessments

To demonstrate the efficacy of durvalumab in combination with platinum-based chemotherapy (paclitaxel and carboplatin) followed by maintenance durvalumab or durvalumab with olaparib when compared to platinum-based chemotherapy by assessment of PFS (using investigator assessment according to Response Evaluation Criteria in Solid Tumours version 1.1 \[RECIST 1.1\]) in patients with newly diagnosed advanced or recurrent endometrial cancer

Time frame: At baseline, every 9 weeks (wks) up to 18 wks, then every 12 wks until objective radiological disease progression. Assessed until 12 Apr 2023 DCO (08 Jul 2024 DCO for China cohort), up to 50 months

Secondary Outcomes

Overall Survival (OS) Analysis

To determine the efficacy of durvalumab in combination with platinum-based chemotherapy (paclitaxel and carboplatin) followed by maintenance durvalumab or durvalumab with olaparib when compared to platinum-based chemotherapy in newly diagnosed advanced or recurrent endometrial cancer patients by assessment of OS

Time frame: Survival assessed every 2 months after RECIST defined radiological progression; assessed through study completion, up to 83 months

Time From Randomisation to Second Progression or Death (PFS2) Based on Local Standard Clinical Practice

Time frame: At baseline, every 9 to 18 wks, then every 12 wks until objective radiological disease progression. Assessments then per local practice every 12 wks until second progression. Assessed until 12Apr2023 DCO (08Jul2024 DCO for China cohort), up to 50 months

Objective Response Rate (ORR) Based on Investigator Assessment

Data from ClinicalTrials.gov

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Placebo tablets to match olaparib

CarboplatinDRUG

Standard of care chemotherapy

PaclitaxelDRUG

Standard of care chemotherapy

Research Site

Tucson, Arizona, United States

Research Site

Concord, California, United States

Research Site

La Jolla, California, United States

Research Site

San Francisco, California, United States

Research Site

Santa Barbara, California, United States

Research Site

Aurora, Colorado, United States

Research Site

Fort Lauderdale, Florida, United States

Research Site

Tampa, Florida, United States

Research Site

Savannah, Georgia, United States

Research Site

Honolulu, Hawaii, United States

...and 191 more locations

Time frame: At baseline, every 9 to 18 wks, then every 12 wks until objective radiological disease progression. Assessed until 12 Apr 2023 DCO (08 Jul 2024 DCO for China cohort), up to 50 months

Duration of Response (DoR) Based on Investigator Assessment

Time frame: At baseline, every 9 wks up to 18 wks, then every 12 wks until objective radiological disease progression. Assessed until 12 Apr 2023 DCO, up to 35 months

Time From Randomisation to First Subsequent Therapy or Death (TFST)

Time frame: Time elapsed from randomisation to first subsequent therapy or death. Assessed every 12 wks following treatment discontinuation, through study completion (up to 83 months)

Time From Randomisation to Second Subsequent Therapy or Death (TSST)

Time frame: Time elapsed from randomisation to second subsequent therapy or death. Assessed every 12 wks following treatment discontinuation, through study completion (up to 83 months)

Time From Randomisation to Discontinuation of Treatment or Death (TDT)

Time frame: Time elapsed from randomisation to study treatment discontinuation or death. Assessed through study completion, up to 83 months

Serum Concentration of Durvalumab

To characterise the pharmacokinetics (PK) of durvalumab and durvalumab in combination with olaparib

Time frame: PK sampling performed on Day 85 pre-dose, Day 183 pre-dose, and 3 months after study treatment discontinuation (up to 36 months)

Anti-drug Antibodies (ADA) to Durvalumab

To characterise the immunogenicity of durvalumab and durvalumab in combination with olaparib

Time frame: Immunogenicity sampling performed on Day 1 pre-dose, Day 85 pre-dose, Day 183 pre-dose, and 3 and 6 months after study treatment discontinuation (up to 39 months)

Change From Baseline in Physical Functioning Score of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer Patients 30 (EORTC QLQ-C30)

To determine effects on symptoms, functioning, and overall health related quality of life (HRQoL) of durvalumab in combination with platinum-based chemotherapy (paclitaxel and carboplatin) followed by maintenance durvalumab or durvalumab with olaparib when compared to platinum-based chemotherapy alone in newly diagnosed advanced or recurrent endometrial cancer patients. The physical functioning score is a score from 0 to 100. Higher scores on the physical functioning score indicate better health status/function.

Time frame: At baseline, every 3 wks until Wk 18, and every 4 wks until the second progression. Assessed until 12 Apr 2023 DCO, up to 35 months. The average treatment effect over the first 12 months after randomisation is presented.

Change From Baseline in Global Health Status/QoL Score of the EORTC QLQ-C30

To determine effects on symptoms, functioning, and overall HRQoL of durvalumab in combination with platinum-based chemotherapy (paclitaxel and carboplatin) followed by maintenance durvalumab or durvalumab with olaparib when compared to platinum-based chemotherapy alone in newly diagnosed advanced or recurrent endometrial cancer patients. 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.