Study of Durvalumab Given With Chemoradiation Therapy in Patients With Unresectable Non-small Cell Lung Cancer

AstraZeneca

Status and phase: Active, not recruiting; Phase 3

Conditions: Non-Small Cell Lung Cancer

Treatments: Other: Placebo; Drug: Durvalumab; Drug: Pemetrexed/ Carboplatin; Drug: Carboplatin/ Paclitaxel; Drug: Cisplatin/ Etoposide; Drug: Pemetrexed/ Cisplatin; Radiation: Radiation

Study type: Interventional

Funder types: Industry

Identifiers

NCT03519971

D933KC00001

2017-004397-34 (EudraCT Number)

Details and patient eligibility

About

This is a Phase III, randomized, double-blind, placebo-controlled, multi-center, international study assessing the efficacy and safety of durvalumab given concurrently with platinum-based CRT (durvalumab + standard of care [SoC] CRT) in patients with locally advanced, unresectable NSCLC (Stage III).

Enrollment: 328 patients

Sex: All

Ages: 18 to 130 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Principal inclusion criteria :

• Subjects with histologically- or cytologically-documented NSCLC
• Locally advanced, unresectable (Stage III) NSCLC
• World Health Organisation (WHO) performance status 0-1
• At least one measurable lesion, not previously irradiated
• Must have a life expectancy of at least 12 weeks at randomization

Principal exclusion criteria :

• Receipt of prior or current cancer treatment, including but not limited to, radiation therapy, investigational agents, chemotherapy, Durvalumab and mAbs.
• Prior exposure to immune-mediated therapy, including but not limited to, other anti CTLA-4, anti-PD-1, anti-PD-L1, and anti PD L2 antibodies, excluding therapeutic anticancer vaccines.
• History of allogeneic organ transplantation
• Active or prior documented autoimmune or inflammatory disorders
• Uncontrolled intercurrent illness
• History of another primary malignancy / leptomeningeal carcinomatosis / active primary immunodeficiency
• Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus
• Mixed small cell and NSCLC histology
• Any medical contraindication to treatment with platinum-based doublet chemotherapy as listed in the local labelling
• Known allergy or hypersensitivity to any of the IPs or any of the IP excipients.
• Patients whose radiation treatment plans are likely to encompass a volume of whole lung receiving ≥20 Gy in total (V20) of more than 35% of lung volume.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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328 participants in 2 patient groups, including a placebo group

Arm 1: Durvalumab + platinum-based chemotherapy and radiation

Experimental group

Description:

Durvalumab ((MEDI4736) in concurrence with platinum-based chemo-radiation therapy. All patients will receive 1 of the following platinum-based standard of care chemotherapy options, based on Investigator discretion, in addition to radiation therapy: * cisplatin/etoposide * carboplatin/paclitaxel * pemetrexed/cisplatin * pemetrexed/carboplatin At the completion of standard of care chemoradiation therapy (SoC CRT), patients with complete response, partial response or stable disease will continue to receive durvalumab as consolidation treatment.

Treatment:

Radiation: Radiation

Drug: Pemetrexed/ Cisplatin

Drug: Cisplatin/ Etoposide

Drug: Pemetrexed/ Carboplatin

Drug: Carboplatin/ Paclitaxel

Drug: Durvalumab

Arm 2: Placebo + platinum-based chemotherapy and radiation

Placebo Comparator group

Description:

Placebo in concurrence with platinum-based chemo-radiation therapy. All patients will receive 1 of the following platinum-based standard of care chemotherapy options, based on Investigator discretion, in addition to radiation therapy: * cisplatin/etoposide * carboplatin/paclitaxel * pemetrexed/cisplatin * pemetrexed/carboplatin At the completion of standard of care chemoradiation therapy (SoC CRT), patients with complete response, partial response or stable disease will continue to receive placebo as consolidation treatment.

Treatment:

Radiation: Radiation

Drug: Pemetrexed/ Cisplatin

Drug: Cisplatin/ Etoposide

Drug: Pemetrexed/ Carboplatin

Drug: Carboplatin/ Paclitaxel

Other: Placebo