A Study to Evaluate the Safety of Concurrent Durvalumab With CRT Followed by Durvalumab for Chinese Unresectable Stage III NSCLC

Study Overview
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Brief Summary
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This is a prospective, multi-center, single arm study assessing the efficacy and safety of durvalumab given concurrently with platinum-based CRT (durvalumab + SoC CRT) in patients with locally advanced, unresectable NSCLC (Stage III).

Detailed Description
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Approximately 35 patients with locally advanced, unresectable NSCLC (Stage III) who are eligible to receive platinum-based CRT will be enrolled in and receive durvalumab + SoC CRT. Patients with CR, partial response (PR), or stable disease (SD）based on Investigator assessment at the 16-week tumor evaluation following completion of SoC CRT will continue to receive durvalumab as consolidation treatment. Patients with RECIST 1.1-defined radiological progressive disease (PD) will proceed to follow-up.

Official Title
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A Prospective Study to Evaluate the Safety of Concurrent Durvalumab (MEDI4736) With Chemoradiation Therapy（CRT）Followed by Durvalumab for Chinese Unresectable Stage III Non Small Cell Lung Cancer（NSCLC）

Conditions
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Unresectable Stage III NSCLC

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with histologically or cytologically-documented NSCLC Locally advanced, unresectable (Stage III) NSCLC World Health Organization (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 Adequate lung function: Pre- or post-bronchodilator forced expiratory volume 1 of 1.0 L or >40% predicted value and DLCO >30% predicted value Must provide an archived tumor tissue block(or at least 15 newly cut unstained slides)≤3 years old; if archived sample unavailable then must provide a recent(≤3 months) tumor biopsy. Exclusion Criteria: Mixed small-cell and NSCLC histology 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. 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 Planned radiation cardiac dose V50>25% Any medical contraindication of platinum-based doublet chemotherapy as listed in the local labelling or known allergy/hypersensitivity to investigational product and/or its excipients History of the following: allogeneic organ transplantation, active or prior autoimmune or inflammatory disorders, another primary malignancy, leptomeningeal carcinomatosis, active primary immunodeficiency Uncontrolled intercurrent illness or active infection

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Durvalumab + platinum-based chemotherapy and radiation<br>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 (intravenous infusion)<br>* Other names: MEDI4736;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 |
| --- | --- | --- |
| Grade ≥3 immune-mediated Adverse event | Grade ≥3 immune-mediated Adverse event | From the date of first dose until disease progression,assessed up to 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | Progression-free survival | From date of first dose until the date of objective disease progression or death,assessed up to 4 years | 
| Overall Survival (OS) | Overall Survival | From the date of first dose until death due to any cause,assessed up to 4 years | 
| Objective response rate(ORR) | Objective response rate | From the date of first dose until the date of objective disease progression or death,assessed up to 4 years | 
| Duration of response(DOR) | Duration of response | 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) | Disease control rate | From the date of first dose until 24 weeks. | 
| Time to death or distant metastasis(TTDM) | Time to death or distant metastasis | From the date of first dose to until the first date of distant metastasis or death in the absence of distant metastasis,assessed up to 4 years |