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RecruitingInterventionalPhase 2

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

NCT ID: NCT05657873Sponsor: Memorial Sloan Kettering Cancer CenterLast updated: 2026-05-07

Summary

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.

Arms & interventions

  • RadiationL-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.

  • BiologicalAnti-PD-(L)1 based immunotherapy

    Standard of care treatment (anti-PD-(L)1 based immunotherapy +/- platinum based chemotherapy

  • DrugPlatinum based chemotherapy

    Standard of care treatment (anti-PD-(L)1 based immunotherapy +/- platinum based chemotherapy

Outcome measures

Primary

  • 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.

    Time frame: up to 4 years

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
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 locations (9)

BAPTIST ALLIANCE - MCI (Data Collection Only)

Miami, Florida, 33143

Recruiting
Adeel Kaiser, MD · Contact

Memorial Sloan Kettering at Basking Ridge (All Protocol Activities)

Basking Ridge, New Jersey, 07920

Recruiting
Paul Romeser, MD · Contact

Memorial Sloan Kettering Monmouth (All Protocol Activities)

Middletown, New Jersey, 07748

Recruiting
Paul Romesser, MD · Contact

Memorial Sloan Kettering Bergen (All protocol activities)

Montvale, New Jersey, 07645

Recruiting
Paul Romesser, MD · Contact

Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities)

Commack, New York, 11725

Recruiting
Paul Romesser, MD · Contact

Memorial Sloan Kettering Westchester (All Protocol Activities)

Harrison, New York, 10604

Recruiting
Paul Romesser, MD · Contact

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065

Recruiting
Paul Romesser, MD · Contact

Memorial Sloan Kettering Nassau (All protocol activities)

Rockville Centre, New York, 11553

Recruiting
Paul Romesser, MD · Contact

Lehigh Valley Health Network (Data Collection Only)

Allentown, Pennsylvania, 18103

Recruiting
Dennis Sopka, MD · Contact

References

  • 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.(PubMed)