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

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）

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).

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.

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