AUSTRAL trial: An open-label, multicenter, phase II study of radiotherapy followed by durvalumab (MEDI4736) and ceralasertib (AZD6738) in stage III NSCLC patients with thoracic relapses +/- oligometastases after PACIFIC regimen.

Non-small cell lung cancer is a leading cause of death for cancer worldwide. Approximately 30% of patients have stage III locally advanced disease at diagnosis. 

Standard treatment for patients for whom surgical resection is not feasible is chemoradiotherapy with platinum-based doublet chemotherapy followed by durvalumab maintenance, which has a survival rate of roughly 50% and a significant percentage of patients encounter disease progression within two years from the onset of maintenance treatment. After the first disease progression, treatment options are limited. 

To address this situation, the AUSTRAL trial aims to explore the safety and efficacy of thoracic re-irradiation of oligometastases followed after an interval of 2 to 4 weeks by durvalumab and ceralasertib in patients with thoracic relapses +/- oligometastases after chemoradiotherapy with platinum-based doublet chemotherapy treatment followed by durvalumab maintenance.

Two primary objectives on safety and efficacy have been set and will be hierarchically analysed.

Primary objective:

• To assess the safety and tolerability, in terms of number of grade 3 or higher adverse events judged as at least possibly related to study treatment regimen (radiotherapy followed by systemic therapy with ceralasertib and durvalumab) within 6 months from the start of study treatment.
• To assess the efficacy in terms of Progression Free Survival (PFS), defined as the time from the date of enrolment until the date of first disease progression or death to any cause, whichever comes first.

Secondary objectives:

• To assess the activity in terms of objective response rate (ORR).
• To assess the efficacy in terms of PFS rate at 6 and 12 months, Overall Survival (OS), OS rate at 6 and 12 months. OS is defined as the time from enrolment until the date of death from any cause.
• To assess the safety and tolerability of the treatment. Adverse events will be encoded and graded using NCI-CTCAE version 5.0.

To assess the efficacy in terms of Progression Free Survival (PFS), defined as the time from the date of enrolment until the date of first disease progression or death to any cause, whichever comes first.

Population: Adult (male or female aged 18 years or older).
Number of Patients: 21 evaluable patients.
Study Population: Stage III NSCLC patients with loco-regional relapse > 12 months from the end of CRT +/- < 3 metastatic lesions after PACIFIC regimen or PACIFIC-like regimens (concurrent or sequential chemo-radiotherapy followed by maintenance durvalumab), regardless of PD-L1 status, but without EGFR, HER-2 or MET exon14 skipping mutations, ALK, ROS1, RET or NTRK rearrangements.
Intervention type: Interventional Study.