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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care

3471 - Neo-adjuvant ipilimumab and nivolumab in high risk resectable bladder urothelial cancer (NABUCCO)

Date

22 Oct 2018

Session

Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care

Topics

Tumour Site

Urothelial Cancers

Presenters

Nick van Dijk

Citation

Annals of Oncology (2018) 29 (suppl_8): viii303-viii331. 10.1093/annonc/mdy283

Authors

N. van Dijk1, C.U. Blank2, P. Kvistborg3, T.N. Schumacher3, E. Hooijberg4, K. Sikorska5, B.V. Rhijn6, M.S. van der Heijden7

Author affiliations

  • 1 Medical Oncology, The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, Amsterdam, 1006 BE - Amsterdam/NL
  • 2 Medical Oncology, The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, 1066 CX - Amsterdam/NL
  • 3 Molecular Oncology And Immunology, The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, 1066 CX - Amsterdam/NL
  • 4 Pathology, The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, Amsterdam, 1066 CX - Amsterdam/NL
  • 5 Biometrics, The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, 1066 CX - Amsterdam/NL
  • 6 Surgical oncology, Het Nederlands Kanker Instituut Antoni van Leeuwenhoek (NKI-AVL), 1006 BE - Amsterdam/NL
  • 7 Medical Oncology, Het Nederlands Kanker Instituut Antoni van Leeuwenhoek (NKI-AVL), 1006 BE - Amsterdam/NL
More

Resources

Abstract 3471

Background

Although muscle-invasive urothelial cancer (UC) can be cured by surgery, recurrence rates are high. Despite impressive response rates to neo-adjuvant cisplatin-based chemotherapy, the absolute overall survival benefit is only 5%. Immunotherapy targeting the PD-1/PD-L1-axis has shown promising activity in UC, particularly when combined with anti-CTLA-4, and patients with lymph node only disease treated with frontline immunotherapy appear to benefit most. Since responses to immunotherapy often appear to be durable, neo-adjuvant immunotherapy may improve prognosis, particularly for high risk N+ disease. Preliminary data on neo-adjuvant pembrolizumab showed remarkable pCR rates (38.9%) and a manageable toxicity profile after 3 cycles of pembrolizumab in resectable T2-3N0 UC, underpinning the potential of neo-adjuvant combination trials for high risk UC.

Trial design

This is a single-arm phase 1B trial to establish whether sequenced pre-operative ipilimumab and nivolumab is safe and effective in high risk UC, defined as upper/lower tract cT3-4aN0 OR ≥T1, cN+ OR ≥T1, any N, resectable retroperitoneal lymph node metastasis. Patients are eligible if they are ≥ 18 years with WHO performance 0-1. Patients must be cisplatin ineligible or refuse cisplatin-based chemo with no previous treatment with PD-(L)1 and CTLA-4 immunotherapy. To mitigate the risk of immune-related toxicity, patients are treated with a mitigated schedule (based on Meerveld-Eggink et al., Ann Oncol 2017): ipi 3 mg/kg (day 1), ipi 3 mg/kg + nivo 1 mg/kg (day 22) and nivo 3 mg/kg (day 43) followed by radical cystectomy or nefro/ureterectomy (day 57-71) with appropriate LN dissection. Six patients will undergo a re-TUR for in-depth analysis of T cell infiltrates. The primary endpoint of this trial is the percentage of patients having surgery <12 weeks after study enrollment. Secondary endpoints are efficacy (pCR) and translational. In total 24 patients will be included. At the time of abstract submission, 5 patients were included.

Clinical trial identification

NCT03387761.

Legal entity responsible for the study

The Netherlands Cancer Institute.

Funding

BMS.

Editorial Acknowledgement

Disclosure

All authors have declared no conflicts of interest.

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