Brigatinib Post Definitive Chemo-radiotherapy in Patients With ALK-fusion Non-small Cell Lung Cancer

BOUNCE is an international multicentre randomised phase II trial. The trial treatment consists of brigatinib 180 mg once daily p.o., with seven day lead-in at 90 mg once daily, for 3 years or until progression of disease. The primary objective of this trial is to evaluate the efficacy in terms of progression-free survival (PFS) for brigatinib consolidation, compared to observation/durvalumab, in patients with unresectable stage III NSCLC and ALK-rearrangement who completed definitive chemo-radiotherapy without disease progression.

Inclusion Criteria:Inclusion criteria for enrolmentPathologically documented, treatment naïve unresectable stage III NSCLCDocumented ALK-fusion, tested locally on tumour tissue by a validated method (DNA NGS, RNA NGS, FISH, IHC, or ctDNA)ECOG Performance Status 0-1Age ≥18 yearsPatient is a candidate to receive chemo-radiotherapy, as per investigator's assessment (including adequate haematological, renal and liver function as per local guidelines).Women of childbearing potential, including women who had their last menstruation in the last 2 years, must have a negative urinary or serum pregnancy test within 5 weeks before enrolment.Ability to comply with the trial protocol, in the investigator's judgment.Written IC for trial participation must be signed and dated by the patient and the investigator prior to any trial-related intervention, including the submission of mandatory biomaterial.Eligibility criteria for randomisation Randomisation of eligible patients must occur within 8 weeks after the last radiotherapy fraction.Completion of thoracic radiotherapyNon-PD at restagingAdequate haematological functionAdequate renal functionAdequate liver and pancreatic functionWomen of childbearing potential, including women who had their last menstruation in the last 2 years, must have a negative urinary or serum pregnancy test before randomisation and should be repeated within 3 days before the first dose of brigatinib.No radiation-pneumonitis of grade ≥2All other AEs from previous chemo-radiotherapy resolved to grade <2 (except for alopecia)ECOG 0-2No major surgery as defined by the investigator within 4 weeks of the the first planned dose of brigatinib.Minor surgical procedures such as catheter placement or minimally invasive biopsies are allowed.No systemic treatment with strong cytochrome p-450 (cyp)3a inhibitors, strong cyp3a inducers, or moderate cyp3a inducers within 14 days before randomisation.Exclusion Criteria:Diagnosis of another primary malignancy other than NSCLC. With the exception of adequately treated non-melanoma skin cancer or cervical cancer in situ; definitively treated non-metastatic prostate cancer; or patients with another primary malignancy who are definitively relapse-free with at least 3 years since the diagnosis of the other primary malignancy.Prior treatment for NSCLCAny evidence of stage IV NSCLCSignificant, uncontrolled, or active cardiovascular diseaseUncontrolled hypertension Patients with hypertension should be under treatment on study entry to control blood pressure.History or the presence at baseline of pulmonary interstitial disease, drug-related pneumonitis.Ongoing or active infection, including, but not limited to, the requirement for intravenous antibiotics.Malabsorption syndrome or other GI illness that could affect oral absorption of brigatinib.Known or suspected hypersensitivity to brigatinib or its excipients.Any concurrent medical condition which, in the opinion of the investigator, would compromise patient safety or interfere with the evaluation of brigatinib.Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements.Women who are pregnant or in the period of lactation.Sexually active men and women of childbearing potential who are not willing to use an effective contraceptive method during the trial until at least 4 months after the last dose of protocol treatment.