Advanced lung cancer
Conditions
Interventions
Dose Escalation Part of BNT324 in Combination With BNT327 (Part I: Single Arm):Participants with histologically or cytologically confirmed recurrent or advanced lung cancer (both SCLC and NSCLC are ac
Randomized Dose Optimization (DO) Cohort and Signal Exploration Cohort (Part II: Randomized Parallel Controlled Trial):BNT324 will be compared in treatment-na?ve participants with advanced metastatic
Sponsors
Jilin Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Participants should provide informed consent by signing and dating the ICF before starting any trial-specific maneuvers. 2. Willing and able to comply with planned visits, treatment schedule, planned trial assessments, lifestyle restrictions, and other requirements of the trial. This includes the participant's ability to understand and follow the instructions related to the trial. 3. Age >=18 years at the time of providing informed consent. 4. Unresectable advanced/metastatic lung cancer confirmed by histological or cytological examination. Histological classification may be based on tumor samples prior to metastatic disease. Participants with mixed histology types must be classified according to the main components. NSCLC participants with any PD-L1 expression or without PD-L1 expression are eligible for the study. Participants with AGA-positive disease must have received targeted therapy prior to enrollment in this trial. 5. Measurable lesions as defined by RECIST 1.1 (see Section 8.3.1 for details). 6. All participants (except SCLC participants) must provide an archival tumor tissue sample (FFPE slide) (Note: For SCLC participants, archival tissue should be provided if possible, but this is not a mandatory requirement for enrollment). Archival tissue may be FFPE tissue blocks or fresh sections obtained from initial diagnosis or at the time of relapse within the past 2 years. If archival tissue is not available, fresh biopsy tissue must be collected prior to C1D1. See the Laboratory Manual for details. 7. ECOG PS score of 0 or 1 (see Section 8.4.4 for details). 8. Expected survival time>=12 weeks. 9. Normal organ and bone marrow function within 7 days prior to randomization/enrollment in the study. To meet the inclusion criteria, all of the following parameters must use the most recently obtained results: Hematology items: (no erythropoietin [EPO], granulocyte colony-stimulating factor [G-CSF], or granulocyte-macrophage colony-stimulating factor [GM-CSF] within 14 days prior to sampling, and no blood, red blood cells, platelet transfusions within 7 days prior to sampling); Items: 9a) Platelet count, laboratory value: >=100,000/mm^3 ; Item: 9b) Hemoglobin, laboratory value: >=9.0 g/dL; Item: 9c) ANC, laboratory test value: >=1,500/mm^3; Blood Biochemistry Items: 9d) Creatinine, laboratory values: estimated creatinine clear>ance calculated using the Cockcroft-Gault formula [(140-age (years)× weight (kg)× (0.85, females only)]/[72× creatinine (mg/dL)] (creatinine unit conversion method: 1 mg/dL = 88.4 µmol/L). 45 mL/min/1.73 m^2(Cockcroft and Gault, 1976); eGFR>45 mL/min/1.73 m^2 calculated using the 2021 CKD-EPI formula (creatinine with or without cystatin C and without racial factors) (Inker et al. 2021); Item: 9e) AST and ALT, laboratory values: =3.0 g/dL; Coagulation function items: 9h) International normalized ratio/prothrombin time and partial thromboplastin time or activated partial thromboplastin time, laboratory examination values: <=1.5×ULN, except for participants receiving anticoagulant therapy, whose international normalized ratio must be within the therapeutic range deemed appropriate by the investigator; 10. Adequate treatment washout period prior to randomization/enrollment, define
Exclusion criteria
Exclusion criteria: 1. Previous B7-H3 targeted therapy. 2. Previous treatment with ADCs containing topoisomerase inhibitors (e.g., datopotamab deruxtecan, detrastuzumab). Note: This exclusion criterion applies to participants with advanced/metastatic lung cancer in the first-line therapy/treatment-naïve cohort. Only participants with advanced/metastatic lung cancer in the second-line treatment cohort with prior ADC therapy with a topoisomerase inhibitor payload are allowed. 3. Candidates (including surgical resection, stereotactic radiotherapy, or tumor ablation) who are considered suitable by the investigator to receive local therapy (including surgical resection, stereotactic radiotherapy, or tumor ablation) that can induce complete response or near complete response and long-term tumor control (sometimes described as "curative" intent). 4. History of severe hematologic toxicity (e.g., grade 4 febrile neutropenia or recurrent/persistent grade 3-4 neutropenia) in the opinion of the investigator as assessed by the investigator. 5. Presence of uncontrolled concomitant or concurrent illness that in the opinion of the investigator would render the participant unable to participate in the trial, limit compliance with trial procedures, or significantly increase the risk of AEs, including: ?bleeding tendency or active bleeding, ?active infection, ?Child-Pugh class B or C cirrhosis, ?pulmonary disease with significant effects on lung function, ?neoplastic emergencies or complications (e.g., malignant hypercalcemia, superior vena cava syndrome, carcinoid syndrome that is unstable and with existing alternative therapies), Psychiatric illness or substance abuse. 6. Uncontrolled or severe cardiovascular disease or diabetes, including any of the following: ?History of unstable angina, acute coronary syndrome, cerebrovascular accident, or other >=3 grade cardiovascular event (within 6 months prior to randomization/enrollment) or symptomatic chronic heart failure (New York Heart Association Cardiac Function Class II-IV). Participants with troponin levels above ULN at screening and without any myocardial infarction-related symptoms should be seen by the College of Cardiology prior to randomization/enrollment to rule out myocardial infarction. ?Central or symptomatic peripheral pulmonary embolism within 3 months prior to randomization/enrollment. Participants with deep vein thrombosis with an incidental diagnosis of peripheral pulmonary artery embolism are eligible for the trial if they are on a stable antithrombotic regimen. ?Participants with uncontrolled hypertension (defined as systolic blood pressure >=160 mm Hg and/or diastolic blood pressure >=100 mm Hg) persisting over time despite antihypertensive therapy, or with a history of hypertensive crisis or hypertensive encephalopathy. ?Uncontrolled and/or clinically significant arrhythmias. ?Corrected QTcF of the Fredericia formula is prolonged to >470 ms (as determined by the average of three 12-lead ECGs during the screening period). ?ECHO or MUGA performed within 28 days prior to randomization/enrollment showing LVEF =13.3 mmol/L [240 mg/dL]). 7. Clinically uncontrollable pleural effusion, ascites, or pericardial effusion within 2 weeks prior to randomization/enrollment requiring drainage, abdominal shunt, or concentrated cell-free ascites reinfusion therapy. 8. History of (non-infectious) ILD/non-infectious pneumonitis requiring steroid therapy, current ILD/non-inf
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective response rate;Dose-limiting toxicity;Overall survival;Treatment-emergent adverse events;Duration of remission;From the first dose of IMP to the first objective remission;Disease control rate;Progression-free survival; | — |
Countries
China
Contacts
Public ContactCheng Ying
Jilin Cancer Hospital
Outcome results
None listed