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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

  • Clinical Investigation
  • Interventional Oncology
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CardioVascular and Interventional Radiology Aims and scope Submit manuscript

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.

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Acknowledgements

The authors thank Gerrit Kracht for his help in producing the figures.

Funding

Contribution in kind by Bristol Myers Squibb and Delcath Systems Inc. Bristol Myers Squibb contributes to the study with the supply of ipilimumab and nivolumab. Delcath Systems contributes to the study by supplying the kits for the percutaneous hepatic perfusion procedure.

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Authors and Affiliations

  1. Department of Medical Oncology, Leiden University Medical Center, Postal Zone C7-P, Albinusdreef 2, 2333ZA, Leiden, The Netherlands

    T. M. L. Tong, F. M. Speetjens, M. A. Jonker-Bos, C. F. M. Roozen, M. Sporrel-Blokland, C. U. Blank & E. Kapiteijn

  2. Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands

    T. M. L. Tong, M. C. Burgmans, A. R. van Erkel, R. W. van der Meer, C. S. P. van Rijswijk, J. Lutjeboer & E. L. van Persijn van Meerten

  3. Department of Medical Oncology, The Netherlands Cancer Institute - Antoni Van Leeuwenhoek Hospital, Amsterdam, The Netherlands

    C. U. Blank

  4. Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands

    C. H. Martini & R. W. M. Zoethout

  5. Department of Extra Corporal Circulation, Leiden University Medical Center, Leiden, The Netherlands

    F. G. J. Tijl

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Correspondence to E. Kapiteijn.

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Conflict of interest

EK and MB have received consultancy fees from Delcath Systems. EK has consultancy/advisory relationships with Bristol Myers Squibb, Novartis, Merck, Pierre Fabre, and received research grants from Bristol Myers Squibb and Pierre Fabre. CB has an advisory role for MSD, Roche, Novartis, GSK, AZ, Pfizer, Lilly, GenMab, Pierre Fabre, Third Rock Ventures, receives research funding from BMS, Novartis, NanoString and 4SC, has stockownership in Immagene BV and a pending patent for WO 2021/177822 A1. The other authors declare no conflict of interest.

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Tong, T.M.L., Burgmans, M.C., Speetjens, F.M. et al. 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. Cardiovasc Intervent Radiol 46, 350–359 (2023). https://doi.org/10.1007/s00270-022-03338-1

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