DURVALUMAB for Stage III non-small cell lung cancer

Inclusion criteria

• {"criterion_text":"- Provision of signed, written and dated informed consent and any locally required authorization\n- Thoracic progression is defined with RECIST criteria v 1.1 in the primary tumor and/or hilar-mediastinal lymph-nodes, with or without a maximum of 3 metastatic lesions amenable to local radiotherapy (at discretion of treating center). Oligomeatses are defined according to the ESTRO criteria.\n- Interval of > 12 months between the end of the first thoracic radiotherapy (PACIFIC or PACIFIC-like)\n- Pre-treatment whole body CT scan and CT-PET scan with i.v. contrast medium, in order to confim intrathoracic relapse +/- oligometastses.\n- Pre-treatment brain MRI to assess brain metastases\n- Evidence of post-menopausal status, or negative urinary/serum pregnancy test for female pre-menopausal patients\n- Patient willing and able to comply with the protocol procedures for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.\n- Male or female aged 18 years or older\n- ECOG Performance Status of 0-2\n- Life expectancy ≥ 6 months at the start of treatment\n- Body weight >30kg\n- Maintenance treatment with durvalumab for a minimum of 3 months\n- Histologically or cytologically documented locally advanced NSCLC at relapse\n- Measurable disease as defined by RECIST v1.1\n- Documented tumor cell PD-L1 status at first diagnosis and/or at relapse"}

Exclusion criteria

• {"criterion_text":"- Patients who discontinued durvalumab due to local or systemic progression during the maintenance phase < 12 months after the end of CRT\n- Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent\n- Concurrent participation (including the follow-up period) in another clinical study with an investigational product or during the last 4 weeks unless it is an observational (non-interventional) clinical study.\n- Any concurrent chemotherapy, immunotherapy, biological or hormonal therapy only for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.\n- Inadequate bone marrow reserve or organ function as defined below: a)\tAbsolute neutrophil count <1.5 x 109/L (1500/mm3) b)\tPlatelets <100 x 109/L (100000/mm3) c)\tHaemoglobin <9.0 g/dL (5.59 mmol/L) d)\tSerum bilirubin <1.5 x upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert’s syndrome (persistent or recurrent hyperbilirubinaemia that is predominantly unconjugated in the absence of evidence of haemolysis or hepatic pathology) who will be allowed in consultation with their physician. e)\tAST and ALT <2.5 x ULN. f)\tInadequate renal function: measured creatinine clearance (CL) <40 ml/min or calculated CL (according to Cockroft-Gault): <40ml/min or by 24-hour urine collection for determination of CL\n- History of active primary immunodeficiency\n- Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion: 1.\tPatients with vitiligo or alopecia 2.\tPatients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement 3.\tAny chronic skin condition that does not require systemic therapy 4.\tPatients without active disease in the last 5 years may be included but only after consultation with the study physician 5.\tPatients with celiac disease controlled by diet alone\n- Female patients who are pregnant, breast-feeding, male, or female patients of reproductive potential who are not employing an effective method of birth control from screening to 90 days after the last dose of durvalumab\n- History of allogenic organ transplantation\n- Any condition that, in the opinion of the Investigator, would interfere with the evaluation of the study drug or interpretation of patient safety or study results\n- 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\n- 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 a. Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician. b. Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Study Physician. c.\tPatients with endocrine AE of ≤Grade 2 are permitted to enroll if they are stably maintained on appropriate replacement therapy and are asymptomatic.\n- Any toxicity that led to permanent discontinuation of prior immunotherapy\n- Patients with more than 3 distant metastases (non-oligometastatic disease)\n- Patients with metastatic disease progression not amenable for radical radiotherapy such as malignant ascites, pleural or pericardial effusion, diffuse lymphangiosis of skin or lung, diffuse bone marrow metastasis, metastasis invading the GI tract, abdominal masses/abdominal organomegaly, identified by physical exam that is not measurable by reproducible imaging techniques.\n- Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.\n- Diagnosis of ataxia telangiectasia\n- Patients harboring targetable genomic alterations, such as EGFR, HER-2 or MET exon14 skipping mutations, ALK, ROS1, RET or NTRK rearrangements. Molecular profiling can be assessed on archival tumor samples or on new tissue or liquid biopsy."}

Primary endpoints

• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Safety/tolerability measured as number of grade 3 or higher adverse events judged at least possibly related to study treatment within 6 months from start of study treatment."}
• {"endpoint_text":"- To assess the efficacy in terms of 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","definition_or_measurement_approach":"Progression-free survival (PFS) defined as time from enrolment to first disease progression or death from any cause."}

Secondary endpoints

• {"endpoint_text":"- To assess the activity in terms of objective response rate (ORR).","definition_or_measurement_approach":"Objective response rate (ORR) measured by response per RECIST v1.1 (implied by measurable disease criterion)."}
• {"endpoint_text":"- To assess the efficacy in terms of PFS rate at 6 and 12 months, OS, OS rate at 6 and 12 months. OS is defined as the time from enrolment until the date of death from any cause.","definition_or_measurement_approach":"PFS rates at 6 and 12 months, overall survival (OS) defined as time from enrolment until date of death from any cause; OS and OS rates measured at 6 and 12 months."}
• {"endpoint_text":"- To assess the safety and tolerability of the treatment.","definition_or_measurement_approach":"Safety and tolerability assessed through adverse event monitoring (grading per NCI CTCAE implied)."}

Italy

Earliest CTIS Part Ii Submission Date

11-06-2025

Latest Decision Or Authorization Date

22-01-2026

Processing Time Days

225

Number Of Sites

7

Number Of Participants

17

Primary sponsor

Full Name

Istituto Di Ricerche Farmacologiche Mario Negri

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

Italy