brigatinib post definitive chemo-radiotherapy in patients with alk-fusion non-small cell lung cancer

Conditions: NSCLC, Stage III; ALK-rearrangement

Summary: 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.


Eligibility criteria:
inclusion criteria: inclusion criteria for enrolment * pathologically documented, treatment naïve unresectable stage iii nsclc * documented alk-fusion, tested locally on tumour tissue by a validated method (dna ngs, rna ngs, fish, ihc, or ctdna) * ecog performance status 0-1 * age ≥18 years * patient 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 radiotherapy * non-pd at restaging * adequate haematological function * adequate renal function * adequate liver and pancreatic function * 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 before randomisation and should be repeated within 3 days before the first dose of brigatinib. * no radiation-pneumonitis of grade ≥2 * all other aes from previous chemo-radiotherapy resolved to grade \<2 (except for alopecia) * ecog 0-2 * no 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 nsclc * any evidence of stage iv nsclc * significant, uncontrolled, or active cardiovascular disease * uncontrolled 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.