A Randomized Phase II Study of Sacituzumab Govitecan Alone, Ivonescimab Alone, or Sacituzumab Govitecan and Ivonescimab in Participants with Previously-Treated Actionable Genomic Alteration Positive Stage IV or Recurrent Non-Small Cell Lung Cancer (Lung-MAP Sub-Study)
Study Description
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.
Eligibility
assigned to S1900N by SWOG SDMC. Assignment to S1900N is determined by submission of NSCLC harboring AGA in LUNGMAP AGA is one of the following genes: ALK, EGFR, HER2 (ERBB2), MET, NTRK, RET, and ROS1.
have measurable disease by CT/MRI. CT from a PET/CT may be used to document only non-measurable disease unless it is of diagnostic quality. Must be assessed within 28 days prior to randomization. Non-measurable disease must be assessed within 42 days prior to randomization. Participants whose only measurable disease is within a previous radiation therapy port must demonstrate clearly progressive disease prior to randomization.
Have a CT or MRI of brain to evaluate for CNS within 42 days.
Participants with spinal cord compression or brain mets must not have residual neurological dysfunction, and the participant has been stable on weaning doses of corticosteroids. Participants with spinal cord compression or brain metastases that requirel treatment must have received treatment to these mets and remained controlled at least 7 days following stereotactic radiation and/or 14 days following whole brain radiation.
Not have leptomeningeal disease that requires CNS-specific treatment prior to randomization and must not be planning to receive the CNS-specific treatment while on study.
Have progressed during or following the most recent line of systemic therapy.
Have previously received an appropriate targeted therapy for the lung cancer AGA
Have previously received Pt-based chemotherapy for stage IV or recurrent disease.
Have received no more than (<=) 3 lines of prior cytotoxic therapy for NSCLC.
Not have received prior TROP2-targeted antibody-drug conjugate or a systemic therapy containing sacituzumab govitecan/SN-38.
Not have received prior anti-PD-1 or anti-PD-L1 antibody therapy.
Not have received any systemic lung cancer therapy within 21 days. Orally administered lung cancer therapies must not have been administered within 10 days
Have completed any prior radiation therapy within 7 days
Have recovered from any side effects of prior therapy
Not be planning to receive any concurrent systemic therapy for lung cancer treatment while receiving treatment on this study
Most recent Zubrod performance status must be 0-1 and be documented within 28 days
Must have a complete medical history and physical exam within 28 days
Absolute neutrophil count 1.5 x 10^3/uL
Hemoglobin >= 10.0 g/dL
Platelets 100 x 10^3/uL
Total bilirubin 1.5 x ULN
AST ALT 3 × ULN
Must have calculated creatinine clearance ≥ 50 mL/min
Known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have assessment of cardiac function
Must not have experienced an arterial or venous thrombotic event or hemoptysis within 28 days
Not be planning to receive warfarin
Not have a prior or concurrent malignancy who has the potential to interfere with the safety or efficacy of the regimen
Not be pregnant or nursing
Must have agreed to use contraceptive method A person who has had menses at any time in the preceding 12 months or who has semen is considered
Known HIV infection must be on effective anti-retroviral therapy and have undetectable viral load test on the most recent test results obtained within 6 months
HBV infection must have undetectable HBV viral load while on suppressive therapy on the most recent test results obtained within 6 months
HCV infection must have been treated and cured. Participants currently being treated for HCV infection must have undetectable HCV viral load test on the most recent test results obtained within 6 months
Must agree to have blood specimens submitted for ctDNA
Must be offered the opportunity to participate in specimen banking
