Non-small Cell Lung Cancer MedDRA version: 21.1 Level: PT Classification code 10029522 Term: Non-small cell lung cancer stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Merck Healthcare KGaA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. = 18 years of age inclusive, at the time of signing the informed consent 2. histologically confirmed diagnosis of advanced NSCLC and: a. Have not received prior systemic therapy treatment for their advanced/Stage IV NSCLC. Completion of treatment with cytotoxic chemotherapy, biological therapy, and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as therapy was completed at least 6 months prior to the diagnosis of metastatic disease. Confirmation of resolution of toxic effects of previous neoadjuvant/adjuvant chemotherapy therapy to Grade = 1. For radiation toxicity or prior major surgeries, participants should have recovered from side effects and/or complications. b. Have measurable disease based on RECIST 1.1 c. Have a life expectancy of at least 3 months d. Availability of tumor tissue (=65 years) yes F.1.3.1 Number of subjects for this age range 292
Exclusion criteria
Exclusion criteria: 1. Participants with nonsquamous NSCLC histologies whose tumor harbors any of the following molecular alterations and targeted therapy is locally approved: a. EGFR sensitizing (activating) mutation b. ALK translocation(s) associated with responsiveness to ALK tyrosine kinase inhibitors c. ROS1 rearrangement(s) associated with responsiveness to ROS1 tyrosine kinase inhibitors d. BRAF V600E mutation 2. Has received major surgery within 4 weeks prior to the first dose of study intervention; received thoracic RT of > 30 Gy within 6 months prior to the first dose of study 7. Known severe hypersensitivity reactions (Grade = 3 National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] v5.0) to investigational product (M7824 or pembrolizumab) or any components in their formulations, or uncontrolled asthma (ie, 3 or more features of partially controlled asthma) 8. Receipt of any organ transplantation 9. Has interstitial lung disease (ILD) OR has had a history of pneumonitis that has required oral or IV steroids 10. Significant acute or chronic infections 11. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with participation for the full duration of the study, or is not in the best interest of the participant, in the opinion of the treating Investigator. Participants with history of bleeding diathesis or recent major bleeding events considered by the Investigator as high risk for investigational drug treatment, such as patients with clinically relevant bleeding events of hemoptysis Grade = 2 within the last month, are also excluded. 12. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways) intervention. 13. Previous malignant disease 14. Has active CNS metastases causing clinical symptoms or metastases that require therapeutic intervention and/or carcinomatosis meningitis 15. Active autoimmune disease that has required systemic treatment in past 1 year OR is receiving systemic steroid therapy < 3 days prior to the first dose of study intervention or receiving any other form of immunosuppressive medication. 16. Is expected to require any other form of systemic or localized antineoplastic therapy while on study (including maintenance therapy with another agent for NSCLC, RT, and/or surgical resection) (other protocol defined criteria could apply)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate improvement in PFS with M7824 compared with pembrolizumab To demonstrate improvement in OS with M7824 compared with pembrolizumab;Secondary Objective: Safety -To evaluate the safety and tolerability of M7824 compared with pembrolizumab Efficacy -To evaluate the objective response of M7824 compared with pembrolizumab - To evaluate the DOR of M7824 compared with pembrolizumab PK -To characterize pharmacokinetic (PK) profile of M7824 Immunogenicity -To characterize the immunogenicity of M7824;Primary end point(s): 1) OR according to RECIST 1.1 assessed by IRC 2) OS;Timepoint(s) of evaluation of this end point: Time from randomization to planned final assessment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 2) OR according to RECIST 1.1 assessed by IRC 3) DOR assessed from CR or PR according to RECIST 1.1 assessed by IRC until PD, death, or last tumor assessment 4) PK profile of M7824 in terms of Ceoi 5 PK profile of M7824 in terms of Ctrough 6) Immunogenicity as measured by ADA assays at Baseline and ontreatment;Timepoint(s) of evaluation of this end point: 1) Time from random. to the last 12-week safety follow-up visit, expected at 47 months. 2) From random. to assessment when 200 OS events occur, OS PA exp. at 49 months from first participant in the study 3) Time from random. to planned final assessment for unconfirmed BOR, exp. 26 months. 4) Time from random. to final assessm.PFS after 192 events at 37 months. 5) Time from CR or PR to planned assessment after 192 PFS events, expected at 37 months. 6,7) Predose samples at Weeks 1,3,5,7, then 6 weekly during treatment; postdose (within 30 min) samples at 6 weekly during treatment and up to study’s Safety Follow-up Visit at 28 days after last study intervention administ. 8) From random. up to study’s Safety Folup Visit, defined as 28 days after last study intervention administr. | — |
Countries
Australia, Belgium, Canada, European Union, Germany, Greece, Italy, Japan, Netherlands, Spain, United States
Contacts
Public ContactCommunication Center Merck KGaA
Merck KGaA
Outcome results
None listed