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Liver Stereotactic Ablative Radiotherapy for Enhancing Immunotherapy Response in Patients with Liver Metastases from Stage IV Non-small Cell Lung Cancer, The HAMMER Trial
Trial Status: active
This phase II trial compares standard drug therapy (immunotherapy with or without chemotherapy) alone with liver stereotactic ablative radiotherapy (L-SABR) and standard drug therapy in patients with stage IV non-small cell lung cancer (NSCLC) that has spread to the liver (liver metastases). L-SABR is a radiation treatment that uses radiotherapy to target liver tumors while limiting the radiation to the surrounding organs. SABR is a form of high-energy x-ray that is focused very precisely on a tumor. Researchers have found that killing liver tumor cells with radiation can boost the immune system’s ability to fight cancer. Combining standard drug therapy with L-SABR may be an effective treatment for people with metastatic NSCLC involving the liver.
Inclusion Criteria
Be greater than 18 years of age on day of signing informed consent
Have a histologically confirmed diagnosis of stage IV NSCLC (includes patients who have progressed on durvalumab for stage III NSCLC) without known mutations in EGFR or BRAF or rearrangements in ALK (anaplastic lymphoma kinase) or ROS-1
Newly diagnosed metastatic non-small cell lung cancer (NSCLC), including both de novo and secondary metastatic disease, with one or more liver metastases
Plan to initiate standard of care anti-PD-(L)1 based immunotherapy +/- platinum based chemotherapy for at least 3 cycles
* Regimens combining anti-CTLA-4 immunotherapy with anti-PD-1 (e.g., ipilimumab plus nivolumab) or anti-PD-L1 (e.g., tremelimumab plus durvalumab) immunotherapy are allowed
Have a performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
Total Bilirubin =< 1.5 x upper limit of normal (ULN)
Aspartate aminotransferase/alanine aminotransferase (AST/ALT) =< 5 x ULN
Eligible for L- SABR to all liver metastases
Patients with known human immunodeficiency virus (HIV) are eligible provided they are under treatment with effective anti-retroviral therapy with CD4 > 200 cells/microliter =< 28 days prior to registration
Exclusion Criteria
Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen should be included
Patients with prior external beam radiation therapy to the liver
Patients with known active hepatitis B or hepatitis C
Patients with immunosuppression including pharmacological immunosuppression with chronic steroids or immune modulators like cyclosporine or methotrexate and patients with active autoimmune disease
Patients who are pregnant or breastfeeding
Men or women not using effective contraception
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT05657873.
I. To determine if liver-stereotactic ablative radiotherapy (L-SABR), when added to first line standard of care anti-PD-(L)1 based immunotherapy +/- chemotherapy, can improve median progression-free survival (PFS) in patients with metastatic non-small cell lung cancer (NSCLC) involving the liver.
SECONDARY OBJECTIVES:
I. To determine safety and tolerability of liver SABR when added to standard of care first line anti-PD-(L)1 based immunotherapy regimens.
II. To compare overall survival (OS) of patients treated with first-line standard of care anti-PD-(L)1 based immunotherapy regimens +/- L-SABR.
III. To compare hepatic progression of patients treated with first-line standard of care anti-PD-(L)1 based immunotherapy regimens +/- L-SABR.
CORRELATIVE OBJECTIVES:
I. To comprehensively profile how L-SABR remodels the systemic T cell response.
II. To characterize how L-SABR remodels the liver tumor immune microenvironment.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM 1: Patients receive standard drug therapy (anti-PD-L1 based immunotherapy with or without platinum based chemotherapy) on study. Patients also undergo computed tomography (CT) or magnetic resonance imaging (MRI) at screening, and undergo CT or fludeoxyglucose F-18 (FDG)-positron emission tomography (PET), collection of blood samples, and biopsy throughout the trial.
ARM 2: Patients undergo L-SABR and receive standard drug therapy (anti-PD-L1 based immunotherapy with or without platinum based chemotherapy) on study. Patients also undergo CT or MRI at screening, and undergo CT or FDG-PET, collection of blood samples, and biopsy throughout the trial.
After completion of study treatment, patients are followed up at 7 weeks, then every 2 months for up to 3 years.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationMemorial Sloan Kettering Cancer Center
