A Prospective, Phase 1 Trial of Nivolumab, Ipilimumab, and Radiotherapy in Patients with Advanced Melanoma
- 1 July 2020
- journal article
- research article
- Published by American Association for Cancer Research (AACR) in Clinical Cancer Research
- Vol. 26 (13), 3193-3201
- https://doi.org/10.1158/1078-0432.ccr-19-3936
Abstract
Purpose: Preclinical data suggest that radiotherapy (RT) is beneficial in combination with immune checkpoint blockade. Clinical trials have explored RT with single-agent immune checkpoint blockade, but no trials have reported RT with the combination of nivolumab and ipilimumab. Patients and Methods: We conducted a phase 1 study of patients with stage IV melanoma receiving nivolumab and ipilimumab with two different dose-fractionation schemes of RT. Patients had at least one melanoma metastasis that would benefit from palliative RT and one metastasis that would not be irradiated. Nivolumab 1 mg/kg + ipilimumab 3 mg/kg and extracranial RT with a dose of 30 Gy in 10 fractions was administered in Cohort A, and then 27 Gy in 3 fractions was administered in Cohort B. The primary outcome was safety. Results: Twenty patients were treated (10 in each cohort). The rates of treatment-related grade 3–4 adverse events in Cohort A and B were 40% and 30%, respectively. There were no grade ≥3 adverse events attributed to RT. Patients responded to treatment outside of the irradiated volume (Cohort A 5/10; Cohort B 1/9). No evaluable patients had progression of irradiated metastases. Immunologic changes were seen in the peripheral blood with increases in T-cell receptor diversity in some responding patients. Conclusions: RT with nivolumab and ipilimumab was safe compared with historical data of nivolumab and ipilimumab alone. Immunologic effects were observed in the peripheral blood. Randomized studies are ongoing to assess whether RT increases the efficacy of nivolumab and ipilimumab.Keywords
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Funding Information
- NIH NCI (P30 CA008748)
- NIH (S10RR027582, 5P30CA124435)
This publication has 31 references indexed in Scilit:
- A Prospective Clinical Trial Combining Radiation Therapy With Systemic Immunotherapy in Metastatic MelanomaInternational Journal of Radiation Oncology*Biology*Physics, 2016
- Lymphocyte-Sparing Effect of Stereotactic Body Radiation Therapy in Patients With Unresectable Pancreatic CancerInternational Journal of Radiation Oncology*Biology*Physics, 2015
- Combined Nivolumab and Ipilimumab or Monotherapy in Untreated MelanomaThe New England Journal of Medicine, 2015
- Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancerNature, 2015
- Combination Therapy with Anti–CTLA-4 and Anti–PD-1 Leads to Distinct Immunologic Changes In VivoThe Journal of Immunology, 2015
- Concurrent Radiotherapy and Ipilimumab Immunotherapy for Patients with MelanomaCancer Immunology Research, 2013
- Developing a Common Language for Tumor Response to Immunotherapy: Immune-Related Response Criteria Using Unidimensional MeasurementsClinical Cancer Research, 2013
- Local Radiation Therapy of B16 Melanoma Tumors Increases the Generation of Tumor Antigen-Specific Effector Cells That Traffic to the TumorThe Journal of Immunology, 2005
- Immune-Mediated Inhibition of Metastases after Treatment with Local Radiation and CTLA-4 Blockade in a Mouse Model of Breast CancerClinical Cancer Research, 2005
- A randomized study comparing two high-dose per fraction radiation schedules in recurrent or metastatic malignant melanomaInternational Journal of Radiation Oncology*Biology*Physics, 1985