A Phase II trial find out the effectiveness and safety of durvalumab combined with olaparib compared to durvalumab alone, in treating patients with metastatic non-small cell lung cancer who have not had worsening of their cancer after treatment with durvalumab and chemotherapy.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

14 Nov 2018 → 28 Jan 2025

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

2024-512769-16-00

EudraCT number

2018-003460-30

ClinicalTrials.gov

NCT03775486

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Pharmacogenomic, Others, Pharmacokinetic, Pharmacogenetic, Efficacy

To assess the efficacy of durvalumab plus olaparib combination therapy compared with durvalumab monotherapy in terms of PFS (Investigator-assessed).

Secondary objectives 6

1. To further assess the efficacy of durvalumab plus olaparib combination therapy compared with durvalumab monotherapy in terms of OS, ORR, and DoR.
2. To further assess the efficacy of durvalumab plus olaparib combination therapy compared with durvalumab monotherapy in terms of PFS (Investigator-assessed) in the HRRm population
3. To assess the PK of durvalumab in combination with olaparib.
4. To assess disease-related symptoms and HRQoL in patients treated with durvalumab plus olaparib combination therapy compared with durvalumab monotherapy
5. To investigate the immunogenicity of durvalumab.
6. Safety objective: To assess the safety and tolerability profile of durvalumab plus olaparib combination therapy compared with durvalumab monotherapy

Conditions and MedDRA coding

Stage IV Non Small Cell Lung Cancer whose tumors lack EGFR mutations and ALK fusions

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Histologically or cytologically documented Stage IV NSCLC not amenable to curative surgery or radiation (according to version 8 of the IASLC Staging Manual in Thoracic Oncology; IASLC Staging Manual in Thoracic Oncology 2016)
2. Patients must have tumors that lack activating EGFR mutations and ALK fusions.
3. (WHO)/(ECOG)performance status of 0 or 1
4. No prior chemotherapy or any other systemic therapy for Stage IV NSCLC
5. Adequate organ and marrow function without blood transfusions in the past 28 days
6. At least 1 tumor lesion, not previously irradiated, that can be accurately measured as perRECIST 1.1. Key Inclusion criteria for randomization to maintenance treatment
7. Documented radiographic evidence of CR, PR, or SD as per Investigator-assessed RECIST1.1 following 4 cycles of platinum-based chemotherapy.
8. CrCl ≥51 mL/min calculated by the investigator or designee using the Cockcroft-Gault equation or measured by 24-hour urine collection.
9. Ability to swallow whole oral medications. Patients not having GI illnesses Please refer to the protocol for rest of inclusion criteria

Exclusion criteria 8

1. Mixed small-cell lung cancer and sarcomatoid variant NSCLC histology
2. Prior exposure to any chemotherapy agents (except chemotherapy or chemoradiation for non-metastatic disease), PARP therapy, or immune-mediated therapy
3. Active or prior documented autoimmune or inflammatory disorders
4. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment.
5. Current or prior use of immunosuppressive medication within 14 days before the first dose of IP
6. untreated (CNS) metastases and/or carcinomatous meningitis
7. Active infection
8. Exclusion criteria to be randomized to maintenance treatment: • Inability to complete 4 cycles of platinum-based chemotherapy for any reason or discontinuation of durvalumab during initial therapy. Please refer to the protocol for rest of exclusion criteria

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression-free survival (PFS) defined as time from date of randomization until the date of objective radiological disease progression according to Investigator assessment using RECIST 1.1 or death (by any cause in the absence of progression)

Secondary endpoints 8

1. Overall survival (OS) defined as time from date of randomization until the date of death by any cause
2. Objective response rate (ORR) defined as percentage of patients with an Investigator-assessed response of CR or PR after randomization
3. Duration of response (DoR) defined as time from the date of first documented response following randomization until the first date of documented progression or death in the absence of disease progression
4. PFS in HRRm population defined as time from date of randomization until the date of objective radiological disease progression according to Investigator assessment in HRRm population using RECIST 1.1 or death (by any cause in the absence of progression)
5. Concentration of durvalumab
6. Disease-related symptoms and HRQoL assessed by change from baseline and time to deterioration (for maintenance phase)in EORTC QLQ-C30 and EORTC QLQ-LC13
7. Presence of anti-drug antibodies (ADA) for durvalumab
8. Safety endpoints of AEs, physical examinations, laboratory findings, and vital signs

Investigational products

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

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

-

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Third parties 1

Locations

1 EU/EEA country · 1 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 7 files

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

Application history

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