Aim of this phase 2 study is to explore the safety and efficacy of thoracic re-irradiation +/- SBRT to oligometastases (\<3) followed after an interval of 2 weeks by durvalumab and ceralasertib for patients with thoracic relapses +/- oligometastases after PACIFIC or PACIFIC-like (concurrent or sequential chemo-radiotherapy followed by maintenance durvalumab) regimens.
Provision of signed, written and dated informed consent and any locally required authorization
Male or female aged 18 years or older
ECOG Performance Status of 0-2
Life expectancy ≥ 6 months at the start of treatment
Patients who discontinued durvalumab due to local or systemic progression during the maintenance phase < 12 months after the end of CRT
Patients who experienced, during the maintenance phase with durvalumab after CRT, grade 3 or more documented immune-related toxicity (with the exception of fully recovered endocrine toxicities) or grade 3 or more radiation-induced pneumonitis.
Any unresolved toxicity NCI CTCAE from previous anticancer therapy not completely resolved or not resolved to baseline prior to screening for this study with the exception of alopecia, vitiligo, and the laboratory values defined below
Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
Single group
Durvalumab (MEDI4736)
DrugDurvalumab will be administered via IV infusion at a dose of 1500 mg on day 8 Q4W until confirmed disease progression unless there is unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met.
Ceralasertib
DrugCeralasertib dose will be administered orally, 240mg BID, approximately 12 ± 2 hours apart, days 1 to 7 q28 (Q4W), up to progression or unacceptable toxicity.
radiotherapy
RadiationLoco-regional recurrences of the primary tumor and regional lymph node metastases will be treated with a total dose of 36 to 50 Gy in daily fractions with a dose of 2 to 3 Gy per fraction. Two weeks from the last dose of radiotherapy, a systemic treatment with durvalumab and ceralasertib will be started.
Safety and tolerability, in terms of number of grade 3 or higher adverse events judged as at least possibly related to study treatment regimen
PFS
PFS is defined as the time from the date of enrolment until the date of first disease progression or death to any cause, whichever comes first.
ORR
Objective response is defined as either complete response (CR) or partial response (PR) as determined by the investigator
Efficacy in terms of PFS rate
Efficacy in terms of OS
OS is defined as the time from enrolment until the date of death from any cause
Efficacy in terms of OS rate
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