Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2023 Mar;46(3):350-359.
doi: 10.1007/s00270-022-03338-1. Epub 2023 Jan 9.

Combining Melphalan Percutaneous Hepatic Perfusion with Ipilimumab Plus Nivolumab in Advanced Uveal Melanoma: First Safety and Efficacy Data from the Phase Ib Part of the Chopin Trial

T M L Tong  1   2 , M C Burgmans  2 , F M Speetjens  1 , A R van Erkel  2 , R W van der Meer  2 , C S P van Rijswijk  2 , M A Jonker-Bos  1 , C F M Roozen  1 , M Sporrel-Blokland  1 , J Lutjeboer  2 , E L van Persijn van Meerten  2 , C H Martini  3 , R W M Zoethout  3 , F G J Tijl  4 , C U Blank  1   5 , E Kapiteijn  6
Affiliations
Clinical Trial

Combining Melphalan Percutaneous Hepatic Perfusion with Ipilimumab Plus Nivolumab in Advanced Uveal Melanoma: First Safety and Efficacy Data from the Phase Ib Part of the Chopin Trial

T M L Tong et al. Cardiovasc Intervent Radiol. 2023 Mar.

Abstract

Purpose: To define a safe treatment dose of ipilimumab (IPI) and nivolumab (NIVO) when applied in combination with percutaneous hepatic perfusion with melphalan (M-PHP) in metastatic uveal melanoma (mUM) patients (NCT04283890), primary objective was defining a safe treatment dose of IPI/NIVO plus M-PHP. Toxicity was assessed according to Common Terminology Criteria for Adverse Events version 4.03 (CTCAEv4.03). Secondary objective was response rate, PFS and OS.

Materials and methods: Patients between 18-75 years with confirmed measurable hepatic mUM according to RECIST 1.1 and WHO performance score 0-1 were included. Intravenous IPI was applied at 1 mg/kg while NIVO dose was increased from 1 mg/kg in cohort 1 to 3 mg/kg in cohort 2. Transarterial melphalan dose for M-PHP was 3 mg/kg (maximum of 220 mg) in both cohorts. Treatment duration was 12 weeks, consisting of four 3-weekly courses IPI/NIVO and two 6-weekly M-PHPs.

Results: Seven patients were included with a median age of 63.6 years (range 50-74). Both dose levels were well tolerated without dose-limiting toxicities or deaths. Grade III/IV adverse events (AE) were observed in 2/3 patients in cohort 1 and in 3/4 patients in cohort 2, including Systemic Inflammatory Response Syndrome (SIRS), febrile neutropenia and cholecystitis. Grade I/II immune-related AEs occurred in all patients, including myositis, hypothyroidism, hepatitis and dermatitis. There were no dose-limiting toxicities. The safe IPI/NIVO dose was defined as IPI 1 mg/kg and NIVO 3 mg/kg. There was 1 complete response, 5 partial responses and 1 stable disease (3 ongoing responses with a median FU of 29.1 months).

Conclusion: Combining M-PHP with IPI/NIVO was safe in this small cohort of patients with mUM at a dose of IPI 1 mg/kg and NIVO 3 mg/kg.

Keywords: Advanced uveal melanoma; Immunotherapy; Liver metastases; Melphalan; Percutaneous hepatic perfusion.

PubMed Disclaimer

References

    1. Singh AD, Turell ME, Topham AK. Uveal melanoma: trends in incidence, treatment, and survival. Ophthalmology. 2011;118(9):1881–5. - DOI - PubMed
    1. van der Kooij MK, Joosse A, Speetjens FM, Hospers GA, Bisschop C, de Groot JW, et al. Anti-PD1 treatment in metastatic uveal melanoma in the Netherlands. Acta Oncol. 2017;56(1):101–3. - DOI - PubMed
    1. Rossi E, Pagliara MM, Orteschi D, Dosa T, Sammarco MG, Caputo CG, et al. Pembrolizumab as first-line treatment for metastatic uveal melanoma. Cancer Immunol Immunother. 2019;68(7):1179–85. - DOI - PubMed - PMC
    1. Algazi AP, Tsai KK, Shoushtari AN, Munhoz RR, Eroglu Z, Piulats JM, et al. Clinical outcomes in metastatic uveal melanoma treated with PD-1 and PD-L1 antibodies. Cancer. 2016;122(21):3344–53. - DOI - PubMed
    1. Kelderman S, van der Kooij MK, van den Eertwegh AJM, Soetekouw PMMB, Jansen RLH, van den Brom RRH, Hospers GAP, Haanen JBAG, Kapiteijn E, Blank CU. Ipilimumab in pretreated metastastic uveal melanoma patients. Results of the dutch working group on immunotherapy of oncology (WIN-O). Acta Oncologica. 2013;52(8):1786–8. https://doi.org/10.3109/0284186X.2013.786839 . - DOI - PubMed

Publication types

LinkOut - more resources