Researchers are looking for new ways to treat metastatic nonsquamous non-small cell lung cancer (NSCLC) that has been treated before. Metastatic means the cancer has spread to other parts of the body. Nonsquamous means the cancer did not start in squamous cells, which are flat cells that line the inside of the lungs.
Standard treatment (usual treatment) for NSCLC is surgery, then immunotherapy with or without chemotherapy after surgery. Immunotherapy is a treatment that helps the immune system fight cancer. Chemotherapy is a medicine that works to destroy cancer cells or stop them from growing.
However, standard treatment may not work or may stop working for some people. Researchers want to know if 2 antibody drug conjugates (ADCs) can help treat metastatic nonsquamous NSCLC that did not respond (get smaller or go away) to treatment. An ADC attaches to specific targets on cancers cells and delivers treatment to destroy those cells.
Researchers will compare 2 different ADCs (the study treatments) to chemotherapy in this study. The goals of this study are to learn:
* About the safety of the study treatments and if people tolerate them * How many people have the cancer respond to the study treatments
Histologically or cytologically confirmed diagnosis of Stage IV nonsquamous non-small cell lung cancer (NSCLC)
Documented disease progression per RECIST 1.1 after receiving an anti-programmed cell death 1 protein (PD-1)/programmed cell death ligand 1 (PD-L1) treatment and platinum-based chemotherapy
Confirmation per local test report that epidermal growth factor receptor negative (EGFR-), anaplastic lymphoma kinase negative (ALK-), c ros oncogene 1 negative (ROS1-), or other directed therapy is not indicated as primary therapy
Measurable disease per RECIST 1.1 as assessed by investigator and verified by BICR
Diagnosis of small cell lung cancer or, for mixed tumors, presence of small cell elements
Received radiation therapy to the lung
Has uncontrolled or significant cardiovascular disorder prior to randomization
Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses
Parallel
Raludotatug Deruxtecan
Biological/VaccineIV Infusion
Ifinatamab Deruxtecan
Biological/VaccineIV Infusion
Docetetaxel
DrugIV Infusion
5-hydroxytryptamine subtype 3 receptor antagonist
DrugAdministered as a rescue medication per approved product label before R-DXd or I-DXd infusion
Neurokinin-1 receptor antagonist
DrugAdministered as a rescue medication per approved product label before R-DXd or I-DXd infusion
Corticosteroid
DrugAdministered as a rescue medication per approved product label before R-DXd or I-DXd infusion, and for 3 days starting 1 day prior to docetaxel administration
Objective Response Rate (ORR)
ORR is defined as the percentage of participants with Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented.
Percentage of Participants with at Least One Adverse Event (AE)
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The percentage of participants who experience an AE will be reported.
Percentage of Participants Who Discontinued Medication Due to an AE
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The percentage of participants who discontinue study intervention due to an AE will be reported.
Duration of Response (DOR)
For participants who demonstrate a confirmed CR (disappearance of all target lesions) or (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). The appearance of one or more new lesions is also considered PD. DOR as assessed by BICR will be presented.
Progression-free Survival (PFS)
PFS is defined as the time from randomization to the first documented PD or death due to any cause, whichever occurs first as assessed by RECIST 1.1. PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by BICR will be presented.
Overall Survival (OS)
OS is defined as the time from randomization to death due to any cause.
Click on the lead sponsor to view all of their trials.
Merck Sharp & Dohme LLC
Lead sponsor
Daiichi Sankyo
Collaborator