BRIGATINIB for Non-small cell lung cancer | ALK-positive non-small cell lung cancer

Inclusion criteria

• {"criterion_text":"- Fully informed written consent and any locally-required authorization (EU Data Privacy Directive) given by the patien\n- Collection of current biopsy during screening must be feasible\n- Women of childbearing potential (WOCBP) must have a negative pregnancy test within 7 days prior to randomization. Women must not be breastfeeding.\n- Female patients who: - are postmenopausal for at least 1 year before the screening visit, OR - are surgically sterile, OR - if they are of childbearing potential, agree to practice highly effective non-hormonal contraception from the time of signing the informed consent through at least 4 months after the last dose of study drug, or agree to completely abstain from heterosexual intercourse. Male patients, even if surgically sterilized (i.e., status post-vasectomy), who: - agree to practice effective barrier contraception during the entire study treatment period and through at least 3 months after the last dose of study drug, OR - agree to completely abstain from heterosexual intercourse.\n- Male or female ≥ 18 years of age\n- Histologically confirmed locally advanced (stage III) and not suitable for curative treatment, i.e. R0 operation or definitive chemo-/radiation, or metastatic (stage IV) ALK+ NSCLC NOTE: Documentation of ALK rearrangement by a positive result of any ALK assay approved in Germany [i.e. positivity for at least one of the three: immunohistochemistry (IHC), NGS, fluorescence in situ hybridisation (FISH)] must be available at baseline. Treatment can already be started based on a local ALK+ test result, but subsequent central testing of the baseline biopsy for molecular profiling, incl. determination of ALK variant and TP53 status, should be made possible for all patients.\n- No prior therapy for metastatic ALK+ NSCLC including therapy with ALK inhibitors. However, 1 or 2 cycles of chemotherapy, chemo-immunotherapy or immunotherapy as well as cerebral irradiation before inclusion in the study will be allowed.\n- At least 1 measurable (i.e., target) lesion per RECIST v1.1 or otherwise evaluable lesion (e.g. brain lesion with at least 5 mm of longest diameter if measured by high-resolution cMRT e.g. using 1 mm slices thickness and not planned for irradiation before the first response assessment).\n- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2\n- Have adequate organ function, as determined by: • Total bilirubin ≤1.5x the upper limit of the normal range (ULN) (< 3x the ULN if Gilbert’s disease is present) • Estimated glomerular filtration rate ≥30 mL/minute/1.73 m2 (calculated by MDRD or any other validated formula, see Appendix 13.4) • Alanine aminotransferase/aspartate aminotransferase ≤2.5x ULN NOTE: ≤5x ULN is acceptable if liver metastases are present. • Serum lipase or serum amylase ≤1.5x ULN • Platelet count ≥75x 109/L • Hemoglobin ≥9 g/dL • Absolute neutrophil count ≥1.5x 109/L\n- Willingness and ability to comply with scheduled visit and study procedures\n- Patient willing to participate in accompanying research program"}

Exclusion criteria

• {"criterion_text":"- History or presence at baseline of pulmonary interstitial disease, drug-related pneumonitis, or radiation pneumonitis\n- Active severe or uncontrolled chronic infection, including but not limited to, the requirement for intravenous antibiotics for longer than 2 weeks\n- History of HIV infection. Testing is not required in the absence of history.\n- Chronic hepatitis B (surface antigen-positive) or chronic active hepatitis C infection. Testing is not required in the absence of history.\n- Any serious medical condition or psychiatric illness that could, in the investigator’s opinion, potentially compromise patient safety or interfere with the completion of treatment according to this protocol\n- Known or suspected hypersensitivity to brigatinib or other TKI or their excipients\n- Life-threatening illness unrelated to cancer\n- Involvement in the planning and/or conduct of the study (applies to both Takeda staff and/or staff of sponsor and study site)\n- Patient who might be dependent on the sponsor, site or the investigator\n- Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities [in accordance with national regulations]\n- Patients who are unable to consent because they do not understand the nature, significance and implications of the clinical trial and therefore cannot form a rational intention in the light of the facts [in accordance with national regulations]\n- Uncontrolled hypertension, defined as hypertension treated* with anti-hypertensive drugs AND blood pressure ≥ 160 mmHg (systolic) or ≥ 100 mmHg (diastolic) in repeated measurements. Untreated elevated blood pressure is not an exclusion criterion and should receive adequate anti-hypertensive adjustment. *Please note: In case of treatment, at least 3 anti-hypertensive drugs should have been used with the intention to control hypertensive disease\n- Legal incapacity or limited legal capacity\n- Females who are pregnant or breastfeeding\n- Patients who have symptomatic CNS metastases (parenchymal or leptomeningeal) at screening or asymptomatic disease requiring an increasing dose of corticosteroids to control symptoms within 7 days prior to randomization. NOTE: If a patient has worsening neurological symptoms or signs due to CNS metastasis, the patient needs to complete local therapy and be neurologically stable (with no requirement for an increasing dose of corticosteroids or use of anticonvulsants) for 7 days prior to randomization.\n- Rare hereditary galactose intolerance, total lactase deficiency or glucose-galactose malabsorption\n- Systemic treatment with strong cytochrome P-450 (CYP) 3A inhibitors, strong CYP3A inducers, or moderate CYP3A inducers or treatment with any investigational systemic anticancer agents, chemotherapy or radiation therapy (except for stereotactic radiosurgery or stereotactic radiation therapy or palliative radiotherapy) within 14 days of randomization\n- Treatment with antineoplastic monoclonal antibodies within 30 days of randomization\n- Major surgery within 30 days of randomization. Minor surgical procedures, such as catheter placement or minimally invasive biopsies, are allowed.\n- Current symptomatic spinal cord compression as confirmed by radiographic imaging. Patients with leptomeningeal disease without symptomatic cord compression are allowed.\n- Significance or uncontrolled cardiovascular disease, defined as to the following: • If an acute myocardial infarction has ensued in the past 6 months, successful reperfusion has to be documented and the patient has to be free of symptoms • New York Heart Association Class III or IV heart failure (i.e. marked limitation in activity due to symptoms, even during less-than-ordinary activity, e.g. walking short distances (20-100 m; comfortable only at rest) within 6 months prior to randomization • Any history of clinically significant ventricular arrhythmia, defined as ventricular tachycardia (VT), ventricular fibrillation (VF), or cardiac arrest\n- Cerebrovascular accident or transient ischemic attack within 6 months prior to first dose of study drug\n- Malabsorption syndrome or other gastrointestinal illness or condition that could affect oral absorption of the study drug"}

Primary endpoints

• {"endpoint_text":"- PFS 1st-line treatment assessed by applying RECIST v1.1","definition_or_measurement_approach":"Assessed by applying RECIST v1.1"}

Secondary endpoints

• {"endpoint_text":"- PFS 2nd-line treatment (RECIST v1.1)","definition_or_measurement_approach":"Assessed by RECIST v1.1"}
• {"endpoint_text":"- TNT 1st line (TNT1, i.e. time-to-next treatment for the 1st line, defined as the time from begin of 1st-line treatment until begin of 2nd-line treatment)","definition_or_measurement_approach":"Time-to-next treatment for 1st line: time from begin of 1st-line treatment until begin of 2nd-line treatment"}
• {"endpoint_text":"- TNT 2nd line (TNT2, i.e. time-to-next treatment for the 2nd line, defined as time from begin of 2nd line until begin of 3rd-line treatment)","definition_or_measurement_approach":"Time-to-next treatment for 2nd line: time from begin of 2nd-line treatment until begin of 3rd-line treatment"}
• {"endpoint_text":"- TNT1/2 (time-to-next treatmemt for the 1st and 2nd line together, defined as time from begin of 1st-line treatment until begin of 3rd-line treatment)","definition_or_measurement_approach":"Time from begin of 1st-line treatment until begin of 3rd-line treatment"}
• {"endpoint_text":"- Overall survival (OS), defined as the time from treatment start in the 1st line to the date of death (due to any cause)","definition_or_measurement_approach":"Time from treatment start in the 1st line to date of death (due to any cause)"}
• {"endpoint_text":"- Efficacy in the CNS (“brain control”) of 1st- and 2nd-line treatment assessed by applying RECIST v1.1 criteria","definition_or_measurement_approach":"Assessed by applying RECIST v1.1 criteria for CNS lesions"}
• {"endpoint_text":"- QoL assessed with SF-12 and EORTC-QLQ-BN20","definition_or_measurement_approach":"Patient-reported quality of life using SF-12 and EORTC-QLQ-BN20 instruments"}
• {"endpoint_text":"- Safety and tolerability including type, incidence and severity of AEs, SAEs","definition_or_measurement_approach":"Capture type, incidence and severity of adverse events (AEs) and serious adverse events (SAEs)"}

Other endpoints

• {"endpoint_text":"- Exploratory endpoint: Capturing ALK fusion variants, TP53 mutation status and „acquired resistance“ mutations via standardized NGS-based multiplex analysis\n- Exploratory endpoint: Efficacy of treatment according to ALK fusion variant and TP53 status\n- Exploratory endpoint: Molecular resistance patterns after 1st-line failure\n- Exploratory endpoint: Impact of 2nd-line treatment after failure of 1st line as defined\n- Exploratory endpoint: Clinical utility of cerebrospinal fluid ctDNA analysis in “brain-only” progression","definition_or_measurement_approach":"Exploratory molecular analyses via standardized NGS-based multiplex analysis to capture ALK fusion variants, TP53 mutation status and acquired resistance mutations; exploratory efficacy analyses stratified by ALK fusion variant and TP53 status; molecular resistance pattern characterization after 1st-line failure; evaluation of 2nd-line treatment impact; assessment of cerebrospinal fluid ctDNA clinical utility in brain-only progression"}

Germany

Earliest CTIS Part Ii Submission Date

17-10-2024

Latest Decision Or Authorization Date

23-10-2024

Processing Time Days

6

Number Of Sites

25

Number Of Participants

118

Primary sponsor

Full Name

Frankfurter Institut Fuer Klinische Krebsforschung IKF GmbH

Organisation Type

Pharmaceutical company

Country Of Registered Address

Germany

Third parties

• {"country":"","full_name":"Takeda Pharmaceutical Company Limited","duties_or_roles":"Source of monetary support","organisation_type":""}