Clinical Trial

. 2024 Feb:133 Suppl 3:57-67.

doi: 10.1111/bju.16190. Epub 2023 Nov 20.

A phase II trial of nivolumab followed by ipilimumab and nivolumab in advanced non-clear-cell renal cell carcinoma

Ciara Conduit¹, Ian D Davis^{1

2

3}, Jeffrey C Goh^{1

4}, Ganessan Kichenadasse^{1

5}, Howard Gurney^{1

6}, Carole A Harris^{1

7

8}, David Pook^{1

9}, Laurence Krieger^{1

10}, Francis Parnis^{1

11}, Craig Underhill^{1

12

13}, Diana Adams^{1

14}, Felicia Roncolato^{1

14

15}, Anthony Joshua^{1

16}, Tom Ferguson^{1

17}, Prashanth Prithviraj^{1

18}, Michelle Morris^{1

19}, Michelle Harrison^{1

20}, Stephen Begbie^{1

21}, Elizabeth Hovey^{1

22

23}, Mathew George^{1

24}, Elizabeth C Liow^{1

9}, Emma K Link^{1

25}, Margaret McJannett¹, Craig Gedye^{1

26}; Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP); UNISoN Investigators

Affiliations

¹ Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Sydney, NSW, Australia.
² Eastern Health Clinical School, Monash University, Box Hill, VIC, Australia.
³ Eastern Health, Melbourne, VIC, Australia.
⁴ Royal Brisbane and Women's Hospital, Herston, QLD, Australia.
⁵ Flinders Centre for Innovation in Cancer, Flinders Medical Centre, Bedford Park, SA, Australia.
⁶ Macquarie University, Sydney, NSW, Australia.
⁷ St George Hospital Cancer Care Centre, Kogarah, NSW, Australia.
⁸ University of NSW South Wales, Sydney, NSW, Australia.
⁹ Monash Health, Melbourne, VIC, Australia.
¹⁰ GenesisCare North Shore, St Leonards, NSW, Australia.
¹¹ Adelaide Cancer Centre, Kurralta Park, SA, Australia.
¹² Border Medical Oncology Research Unit, Albury Wodonga Regional Cancer Centre, East Albury, NSW, Australia.
¹³ Rural Medical School, Albury Campus, University of New South Wales, Albury-Wodonga, NSW, Australia.
¹⁴ Macarthur Cancer Therapy Centre, Campbelltown, NSW, Australia.
¹⁵ NHMRC Clinical Trials Centre, University of Sydney, Camperdown, NSW, Australia.
¹⁶ St Vincent's Hospital Sydney, Darlinghurst, NSW, Australia.
¹⁷ Fiona Stanley Hospital, Perth, WA, Australia.
¹⁸ Ballarat Oncology and Haematology Services, Ballarat, VIC, Australia.
¹⁹ Sunshine Coast University Hospital, Birtinya, QLD, Australia.
²⁰ Royal Prince Alfred Hospital, Hunters Hill, NSW, Australia.
²¹ North Coast Cancer Institute, Port Macquarie Base Hospital, Port Macquarie, NSW, Australia.
²² Nelune Comprehensive Cancer Centre, Prince of Wales Hospital, Randwick, Sydney, NSW, Australia.
²³ Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
²⁴ Northwest Cancer Centre, Tamworth Hospital, Tamworth, NSW, Australia.
²⁵ Centre for Biostatistics and Clinical Trials (BaCT), Peter MacCallum Cancer Centre, The University of Melbourne, Melbourne, VIC, Australia.
²⁶ Calvary Mater Newcastle, Waratah, NSW, Australia.

PMID: 37986556
DOI: 10.1111/bju.16190

Clinical Trial

A phase II trial of nivolumab followed by ipilimumab and nivolumab in advanced non-clear-cell renal cell carcinoma

Ciara Conduit et al. BJU Int. 2024 Feb.

. 2024 Feb:133 Suppl 3:57-67.

doi: 10.1111/bju.16190. Epub 2023 Nov 20.

Authors

Affiliations

¹ Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Sydney, NSW, Australia.
² Eastern Health Clinical School, Monash University, Box Hill, VIC, Australia.
³ Eastern Health, Melbourne, VIC, Australia.
⁴ Royal Brisbane and Women's Hospital, Herston, QLD, Australia.
⁵ Flinders Centre for Innovation in Cancer, Flinders Medical Centre, Bedford Park, SA, Australia.
⁶ Macquarie University, Sydney, NSW, Australia.
⁷ St George Hospital Cancer Care Centre, Kogarah, NSW, Australia.
⁸ University of NSW South Wales, Sydney, NSW, Australia.
⁹ Monash Health, Melbourne, VIC, Australia.
¹⁰ GenesisCare North Shore, St Leonards, NSW, Australia.
¹¹ Adelaide Cancer Centre, Kurralta Park, SA, Australia.
¹² Border Medical Oncology Research Unit, Albury Wodonga Regional Cancer Centre, East Albury, NSW, Australia.
¹³ Rural Medical School, Albury Campus, University of New South Wales, Albury-Wodonga, NSW, Australia.
¹⁴ Macarthur Cancer Therapy Centre, Campbelltown, NSW, Australia.
¹⁵ NHMRC Clinical Trials Centre, University of Sydney, Camperdown, NSW, Australia.
¹⁶ St Vincent's Hospital Sydney, Darlinghurst, NSW, Australia.
¹⁷ Fiona Stanley Hospital, Perth, WA, Australia.
¹⁸ Ballarat Oncology and Haematology Services, Ballarat, VIC, Australia.
¹⁹ Sunshine Coast University Hospital, Birtinya, QLD, Australia.
²⁰ Royal Prince Alfred Hospital, Hunters Hill, NSW, Australia.
²¹ North Coast Cancer Institute, Port Macquarie Base Hospital, Port Macquarie, NSW, Australia.
²² Nelune Comprehensive Cancer Centre, Prince of Wales Hospital, Randwick, Sydney, NSW, Australia.
²³ Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
²⁴ Northwest Cancer Centre, Tamworth Hospital, Tamworth, NSW, Australia.
²⁵ Centre for Biostatistics and Clinical Trials (BaCT), Peter MacCallum Cancer Centre, The University of Melbourne, Melbourne, VIC, Australia.
²⁶ Calvary Mater Newcastle, Waratah, NSW, Australia.

PMID: 37986556
DOI: 10.1111/bju.16190

Abstract

Objective: To evaluate the efficacy of sequential treatment with ipilimumab and nivolumab following progression on nivolumab monotherapy in individuals with advanced, non-clear-cell renal cell carcinoma (nccRCC).

Materials and methods: UNISoN (ANZUP1602; NCT03177239) was an open-label, single-arm, phase 2 clinical trial that recruited adults with immunotherapy-naïve, advanced nccRCC. Participants received nivolumab 240 mg i.v. two-weekly for up to 12 months (Part 1), followed by sequential addition of ipilimumab 1 mg/kg three-weekly for four doses to nivolumab if disease progression occurred during treatment (Part 2). The primary endpoint was objective tumour response rate (OTRR) and secondary endpoints included duration of response (DOR), progression-free (PFS) and overall survival (OS), and toxicity (treatment-related adverse events).

Results: A total of 83 participants were eligible for Part 1, including people with papillary (37/83, 45%), chromophobe (15/83, 18%) and other nccRCC subtypes (31/83, 37%); 41 participants enrolled in Part 2. The median (range) follow-up was 22 (16-30) months. In Part 1, the OTRR was 16.9% (95% confidence interval [CI] 9.5-26.7), the median DOR was 20.7 months (95% CI 3.7-not reached) and the median PFS was 4.0 months (95% CI 3.6-7.4). Treatment-related adverse events were reported in 71% of participants; 19% were grade 3 or 4. For participants who enrolled in Part 2, the OTRR was 10%; the median DOR was 13.5 months (95% CI 4.8-19.7) and the median PFS 2.6 months (95% CI 2.2-3.8). Treatment-related adverse events occurred in 80% of these participants; 49% had grade 3, 4 or 5. The median OS was 24 months (95% CI 16-28) from time of enrolment in Part 1.

Conclusions: Nivolumab monotherapy had a modest effect overall, with a few participants experiencing a long DOR. Sequential combination immunotherapy by addition of ipilimumab in the context of disease progression to nivolumab in nccRCC is not supported by this study, with only a minority of participants benefiting from this strategy.

Keywords: carcinoma; clinical trial; immunotherapy; kidney neoplasms; renal cell.

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Conflict of interest statement

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Ciara Conduit: honoraria (AstraZeneca, Limbic). Ian D. Davis: participation on data safety monitoring board/advisory boards, including Ipsen (advisory board; unpaid), MSD (RCC virtual advisory board; unpaid), Merck/Pfizer (APAC GU advisory board; unpaid), Merck/Pfizer (avelumab advisory board; unpaid), Eisai (RCC virtual advisory board; unpaid) and Bristol Myers Squibb (RCC advisory board; unpaid); leadership or fiduciary roles in other board/society/committee (ANZUP Cancer Trials Group, Director and Board Chair; unpaid). Jeffrey Goh: honoraria (GSK, MSD, Pfizer-Merck Serono, Janssen, Ipsen); advisory boards (GSK, BMS). Howard Gurney: participation on advisory boards (Astra Zeneca, Pfizer, MSH, Merck Serono, Ipsen, Astellas); honoraria (MSD, Merck Serono, Pfizer). Francis Parnis: honoraria (Bayer, Merck, Pfizer, Astra Zeneca); travel support (Bayer); advisory boards (Janssen, Merck). Anthony Joshua: stocks (Pricilium Therapeutics); consulting/advisory roles, with all funds donated to institution (Neolukin, Janssen Oncology, Astra Zeneca, Sanofi, Noxopharm, Pfizer, Novartis, Bristol Myers Squibb, Merck Serono, Eisai, Ideaya, IQvia); research funding (Bristol Myers Squibb, Janssen Oncology, Merck Sharp & Dohme, Mayne Pharma, Roche/Genentech, Bayer, Macrogenics, Lilly, Pfizer, Astra Zeneca, Corvus Pharmaceuticals, Lilly); patents/royalties/other IP (cancer therapeutic methods). Tom Ferguson: support for meeting attendance including from BMS (ESMO virtual meeting registration), Pfizer (ANZUP ASM registration), MSD (registration to ASCO GU virtual meeting, ESMO virtual meeting, ASCO ASM virtual meeting x2). Michelle Harrison: stocks (CSL); consulting/advisory (MSD, Eisai). Elizabeth Hovey: advisory boards including Ipsen, Bayer Australia, Merck Healthcare, Janssen-Cilag. Elizabeth Liow: support for meeting attendance from Pfizer (ASCO GU). Emma K. Link: data safety monitoring board (CARE NSW). Craig Gedye: honoraria from various companies with all funds donated to ANZUP (BMS, Ipsen, BMS) or Red Cross (Limbic); research funding to third party (BMS, Amgen, Merck Sharp & Dohme, advisory committee (unremunerated) from ANZUP, COGNO, International Kidney Cancer Consortium, Mark Hughes Foundation); consulting roles (Cadex Genomics, BCAL diagnostics, Novotech-CRO). The remaining authors have no potential conflicts of interest.

References

1. Motzer RJ, McDermott DF, Escudier B et al. Conditional survival and long-term efficacy with nivolumab plus ipilimumab versus sunitinib in patients with advanced renal cell carcinoma. Cancer 2022; 128: 2085-2097
1. Motzer RJ, Escudier B, McDermott DF et al. Nivolumab versus Everolimus in advanced renal-cell carcinoma. N Engl J Med 2015; 373: 1803-1813
1. Motzer RJ, Tannir NM, McDermott DF et al. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med 2018; 378: 1277-1290
1. Choueiri TK, Powles T, Burotto M et al. Nivolumab plus cabozantinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med 2021; 384: 829-841
1. Motzer R, Alekseev B, Rha SY et al. Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma. N Engl J Med 2021; 384: 1289-1300

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A phase II trial of nivolumab followed by ipilimumab and nivolumab in advanced non-clear-cell renal cell carcinoma

Affiliations

A phase II trial of nivolumab followed by ipilimumab and nivolumab in advanced non-clear-cell renal cell carcinoma

Authors

Affiliations

Abstract

Conflict of interest statement

References

Publication types

MeSH terms

Substances

Supplementary concepts

Grants and funding

LinkOut - more resources

Full Text Sources