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

Study Overview
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Brief Summary
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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).

Official Title
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A Phase III, Randomized, Placebo-controlled, Double-blind, Multi-center, International Study of Durvalumab Given Concurrently With Platinum-based Chemoradiation Therapy in Patients With Locally Advanced, Unresectable NSCLC (Stage III) (PACIFIC2)

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Durvalumab
* Other: Placebo
* Drug: Cisplatin/ Etoposide
* Drug: Carboplatin/ Paclitaxel
* Drug: Pemetrexed/ Cisplatin
* Drug: Pemetrexed/ Carboplatin
* Radiation: Radiation


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 130 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: Durvalumab + platinum-based chemotherapy and radiation<br>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. | Drug: Durvalumab<br>* Durvalumab IV (intravenous infusion)<br>* Other names: MEDI4736;Drug: Cisplatin/ Etoposide<br>* Cisplatin/ Etoposide, as per standard of care<br>Drug: Carboplatin/ Paclitaxel<br>* Carboplatin /Paclitaxel, as per standard of care<br>Drug: Pemetrexed/ Cisplatin<br>* Pemetrexed / Cisplatin, as per standard of care<br>Drug: Pemetrexed/ Carboplatin<br>* Pemetrexed / Carboplatin , as per standard of care<br>Radiation: Radiation<br>* 5 fractions/ week for  6 weeks (±3 days) (Total 60 Gy)<br>|
| Placebo Comparator: Arm 2: Placebo + platinum-based chemotherapy and radiation<br>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. | Other: Placebo<br>* Placebo IV (intravenous infusion)<br>Drug: Cisplatin/ Etoposide<br>* Cisplatin/ Etoposide, as per standard of care<br>Drug: Carboplatin/ Paclitaxel<br>* Carboplatin /Paclitaxel, as per standard of care<br>Drug: Pemetrexed/ Cisplatin<br>* Pemetrexed / Cisplatin, as per standard of care<br>Drug: Pemetrexed/ Carboplatin<br>* Pemetrexed / Carboplatin , as per standard of care<br>Radiation: Radiation<br>* 5 fractions/ week for  6 weeks (±3 days) (Total 60 Gy)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) |  | From date of randomization until the date of objective disease progression or death, assessed up to 4 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) |  | From the date of randomization until death due to any cause, assessed up to 4 years. | 
| Objective Response Rate (ORR) |  | From the date of Randomisaton until the date of objective disease progression or death, assessed up to 4 years | 
| Overall Survival at 24 months |  | From the date of randomization until 24 months | 
| Rate of complete response |  | From the date of Randomisaton until the date of objective disease progression or death, assessed up to 4 years | 
| Duration of response (DoR) |  | From the date of first documented response (RECIST 1.1.) until the first date of documented progression or death in the absence of disease progression, assessed up to 4 years. | 
| Disease Control Rate (DCR) |  | From the date of randomization until 24 weeks. | 
| Time from randomization to second progression PFS2 |  | From the date of randomization to the earliest progression event subsequent to that used for the PFS endpoint or death, up to 4 years | 
| Time to death or distant metastasis (TTDM) |  | From the date of randomization to until the first date of distant metastasis or death in the absence of distant metastasis, assessed up to 4 years | 
| Presence of ADA for durvalumab in combination with CRT |  | From the date of randomization until 6 months after date of last IP dose. | 
| To assess symptoms and health-related QoL in patients treated with durvalumab + SoC CRT compared with placebo + SoC CRT using EORTC QLQ-C30 v3 |  | From the date of randomisation until PFS2. | 
| To assess symptoms and health-related QoL in patients treated with durvalumab + SoC CRT compared with placebo + SoC CRT using QLQ-LC13 |  | From the date of randomisation until PFS2. | 
| To assess the PK of durvalumab in blood (peak trough concentration) when in combination with CRT |  | From the date of randomization until 3 months after date of last IP dose. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Locally Advanced, Unresectable NSCLC, Carcinoma, NSCLC