This phase II Expanded Lung-MAP treatment trial compares how well sacituzumab govitecan alone, ivonescimab alone, or sacituzumab govitecan in combination with ivonescimab works in treating patients with non-small cell lung cancer (NSCLC) that has come back after a period of improvement (recurrent) or is stage IV and has a change in at least 1 of these genes: ALK, EGFR, HER2 (ERBB2), MET, NTRK, RET, and ROS1. This type of gene change is called an actionable genomic alteration (AGA), which means certain treatments can target the change to fight the cancer. Sacituzumab govitecan is a monoclonal antibody, called sacituzumab, linked to a toxic drug called SN-38. Sacituzumab govitecan is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of tumor cells, known as TROP2 receptors, and delivers SN-38 to kill them. Ivonescimab is a bispecific antibody that can bind to two different antigens at the same time. It binds to programmed cell death protein 1 (PD1), a protein found on the surface of T cells (a type of white blood cell) and vascular endothelial growth factor (VEGF), a protein found on the surface of tumor cells. Ivonescimab may strengthen the immune system and interfere with the ability of tumor cells to grow and spread. Giving a combination of sacituzumab govitecan and ivonescimab work better than either drug alone, and sacituzumab govitecan alone, ivonescimab alone, or sacituzumab govitecan and ivonescimab together may work better than standard treatments at shrinking NSCLC with an AGA.
Participants must have been assigned to S1900N by the Southwest Oncology Group (SWOG) Statistics and Data Management Center (SDMC). Assignment to S1900N is determined by submission of documentation of NSCLC harboring an actionable genomic alteration (AGA) in the LUNGMAP protocol. AGA is defined in this protocol as an activating driver alteration with an approved targeted therapy for lung cancer in one of the following genes: ALK, EGFR, HER2 (ERBB2), MET, NTRK, RET, and ROS1.
Participants must have measurable disease documented by CT or MRI. The CT from a combined positron emission tomography (PET)/CT may be used to document only non-measurable disease unless it is of diagnostic quality. Measurable disease must be assessed within 28 days prior to randomization. Pleural effusions, ascites and laboratory parameters are not acceptable as the only evidence of disease. Non-measurable disease must be assessed within 42 days prior to randomization. All disease must be assessed and documented on the Baseline Tumor Assessment Form. Participants whose only measurable disease is within a previous radiation therapy port must demonstrate clearly progressive disease (in the opinion of the treating investigator) prior to randomization.
Participants must have a CT or MRI scan of the brain to evaluate for CNS disease within 42 days prior to randomization.
Participants with spinal cord compression or brain metastases must not have residual neurological dysfunction, unless no further recovery is expected, and the participant has been stable on weaning doses of corticosteroids (≤ 10 mg daily prednisone or equivalent) prior to randomization. Participants with spinal cord compression or brain metastases that require local treatment must have received local treatment to these metastases and remained clinically controlled and asymptomatic for at least 7 days following stereotactic radiation and/or 14 days following whole brain radiation, and prior to randomization.
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SWOG Cancer Research Network
Lead sponsor
National Cancer Institute (NCI)
Collaborator