A Study of Targeted Radiation Therapy in People With Non-Small Cell Lung Cancer (NSCLC)

A Phase II Trial of Hepatic Ablation of Metastases to Modulate and Enhance Immunotherapy Response (HAMMER) in NSCLC

The purpose of this study is to see whether adding liver stereotactic ablative radiotherapy/L-SABR to standard drug therapy is better than standard drug therapy alone for people with metastatic non-small cell lung cancer/NSCLC.

Study Overview

• Status: Recruiting
• Conditions: NSCLC; Non Small Cell Lung Cancer; Non Small Cell Lung Cancer Metastatic; NSCLC Stage IV; Non-small Cell Carcinoma
• Intervention / Treatment: Radiation: L-SABR; Biological: Anti-PD-(L)1 based immunotherapy; Drug: Platinum based chemotherapy

• Study Type: Interventional
• Enrollment (Estimated): 68
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Daniel Gomez, MD; Phone Number: 212-639-2087; Email: gomezd@mskcc.org
• Study Contact Backup: Name: Paul Romesser, MD; Phone Number: 646-888-2118; Email: romessep@mskcc.org

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33143
      • Recruiting
      • BAPTIST ALLIANCE - MCI (Data Collection Only)
      • Contact: Adeel Kaiser, MD; Phone Number: 786-596-2000
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Recruiting
      • Memorial Sloan Kettering at Basking Ridge (All protocol activities)
      • Contact: Paul Romeser, MD; Phone Number: 646-888-2118
    • Middletown, New Jersey, United States, 07748
      • Recruiting
      • Memorial Sloan Kettering Monmouth (All protocol activities)
      • Contact: Paul Romesser, MD; Phone Number: 646-888-2118
    • Montvale, New Jersey, United States, 07645
      • Recruiting
      • Memorial Sloan Kettering Bergen (All protocol activities)
      • Contact: Paul Romesser, MD; Phone Number: 646-888-2118
  • New York
    • Commack, New York, United States, 11725
      • Recruiting
      • Memorial Sloan Kettering Suffolk - Commack (Limited protocol activities)
      • Contact: Paul Romesser, MD; Phone Number: 646-888-2118
    • Harrison, New York, United States, 10604
      • Recruiting
      • Memorial Sloan Kettering Westchester (All protocol activities)
      • Contact: Paul Romesser, MD; Phone Number: 646-888-2118
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center (All Protocol Activities)
      • Contact: Paul Romesser, MD; Phone Number: 646-888-2118
    • Rockville Centre, New York, United States, 11553
      • Recruiting
      • Memorial Sloan Kettering Nassau (All protocol activities)
      • Contact: Paul Romesser, MD; Phone Number: 646-888-2118
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Recruiting
      • Lehigh Valley Health Network (Data Collection Only)
      • Contact: Dennis Sopka, MD; Phone Number: 610-402-0700

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

  o Patients with recurrent metastatic NSCLC following prior durvalumab for stage III disease are eligible provided this is their first immunotherapy course for metastatic disease (i.e., the planned anti-PD-(L)1-based regimen represents first-line systemic therapy in the metastatic setting).

• 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

  o 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 ECOG Performance Scale.

• Liver function tests:

  • Total Bilirubin ≤ 1.5 x ULN
  • AST/ ALT ≤ 5 x ULN
• Eligible for L- SABR to all liver metastases as determined by the treating radiation oncologist
• Patients with known HIV are eligible provided they are under treatment with effective anti-retroviral therapy with CD4 count >200 cells/microliter within 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 cyclosporin or methotrexate and patients with active autoimmune disease.
• Patients who are pregnant or breastfeeding
• Men or women not using effective contraception.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: L-SABR Arm; Participants randomized to the experimental arm will continue with standard of care treatment but will also undergo radiation simulation for L-SABR/Liver Stereotactic Ablative Radiation Therapy.	Radiation: L-SABR; L-SABR will be delivered in a week during which the patient receives no chemotherapy. L-SABR can be on the same week or even day as anti-PD-(L)1 therapy.; Other Names: Liver Stereotactic Ablative Radiation Therapy; Biological: Anti-PD-(L)1 based immunotherapy; Standard of care treatment (anti-PD-(L)1 based immunotherapy +/- platinum based chemotherapy; Other Names: Standard of Care; Drug: Platinum based chemotherapy; Standard of care treatment (anti-PD-(L)1 based immunotherapy +/- platinum based chemotherapy; Other Names: Standard of Care
Active Comparator: Control Arm; Participants randomized to the control arm will be treated according to the standard of care.	Biological: Anti-PD-(L)1 based immunotherapy; Standard of care treatment (anti-PD-(L)1 based immunotherapy +/- platinum based chemotherapy; Other Names: Standard of Care; Drug: Platinum based chemotherapy; Standard of care treatment (anti-PD-(L)1 based immunotherapy +/- platinum based chemotherapy; Other Names: Standard of Care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median progression-free survival	Primary outcomes is to determine if 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 NSCLC involving the liver.	up to 4 years

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Investigators: Principal Investigator: Paul Romesser, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

General Publications

• McMillan MT, Reyngold M, Crane CH, O'Brien DAR, Williams VM, Zinovoy M, Cuaron JJ, Gonen M, Kaiser A, Sopka DM, Gomez DR, Schoenfeld AJ, Bott M, Romesser PB. A phase II trial of hepatic ablation of metastases to modulate and enhance immunotherapy response in non-small cell lung cancer (HAMMER-NSCLC). BMC Cancer. 2025 Sep 2;25(1):1408. doi: 10.1186/s12885-025-14779-5.

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2022
• Primary Completion (Estimated): December 9, 2026
• Study Completion (Estimated): December 9, 2026

Study Registration Dates

• First Submitted: December 12, 2022
• First Submitted That Met QC Criteria: December 12, 2022
• First Posted (Actual): December 20, 2022

Study Record Updates

• Last Update Posted (Actual): May 7, 2026
• Last Update Submitted That Met QC Criteria: May 6, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: NSCLC; Memorial Sloan Kettering Cancer Center; non small cell lung cancer; NSCLC Stage IV; Non Small Cell Lung Cancer Metastatic; Non-small Cell Carcinoma; liver stereotactic ablative radiotherapy; L-SABR; 22-368
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Health Services Administration; Health Care Quality, Access, and Evaluation; Quality of Health Care; Quality Indicators, Health Care; Inorganic Chemicals; Standard of Care; Platinum Compounds
• Other Study ID Numbers: 22-386

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes