Abstract 1481TiP
Background
Surgery is currently the only curative treatment of locally advanced renal cell carcinoma (RCC). Despite surgical resection, intermediate- to high-risk patients still can develop disease recurrence or systemic progression. These patients may benefit from adjuvant or neoadjuvant treatment options. Based on promising results in metastatic disease, immune checkpoint inhibition could be a good therapeutic strategy for the perioperative setting. Preclinical data and early clinical studies in melanoma suggest a greater efficacy of neoadjuvant immunotherapy compared to the adjuvant approach. This trial was designed to treat RCC patients who are at risk for recurrence or distant metastases with different neoadjuvant immunotherapy combinations to obtain the most efficacious and least toxic treatment option for this setting.
Trial design
This randomized, open-label, three-arm phase 2 trial aims to assess the efficacy and safety of neoadjuvant nivolumab alone or in combination in intermediate- to high-risk non-metastatic clear cell RCC using an adaptive trial design. A maximum number of 69 patients will be randomized to receive either 2 courses nivolumab 360 mg, 2 courses ipilimumab 1 mg/kg + nivolumab 3 mg/kg or 2 courses of nivolumab 360 mg + relatlimab 360 mg every three weeks prior to surgery. The primary endpoint is pathologic response rate defined as the proportion of patients demonstrating a complete or partial pathologic response. Secondary endpoints include safety, objective response rate, recurrence-free survival, event-free survival, rate of distant metastases and local recurrences and surgical morbidity. Blood samples, pretreatment biopsies and post-treatment tumor tissue will be collected for translational research. After 42 patients have been recruited (14 per arm), an interim analysis will be performed to evaluate the observed efficacy and toxicity within each arm and either allow for early discontinuation or continuing recruitment in the second stage of a Simon’s two stage design. The first patient was enrolled in April 2022.
Clinical trial identification
NCT05148546, Registered December 8, 2021.
Editorial acknowledgement
Legal entity responsible for the study
NKI-AVL - Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital.
Funding
Bristol Myers Squibb (BMS).
Disclosure
C.U. Blank: Financial Interests, Institutional, Advisory Board: BMS, MSD, Roche, Novartis, GSK, AZ, Pfizer, Lilly, GenMab, Pierre Fabre; Financial Interests, Personal, Expert Testimony: Third Rock Ventures; Financial Interests, Personal, Stocks/Shares: Uniti Cars, co-founder Immagene BV; Financial Interests, Institutional, Invited Speaker: BMS, Novartis, NanoString, 4SC. A. Bex: Financial Interests, Institutional, Research Grant, Restricted educational grant for an investigator initiated trial of neoadjuvant therapy in high risk renal cancer: Pfizer; Non-Financial Interests, Principal Investigator, Steering committee member and PI in an adjuvant trial: Roche/Genentech; Non-Financial Interests, Principal Investigator, Steering committee member and local investigator in an adjuvant trial: BMS; Non-Financial Interests, Advisory Role, Medical Steering committee member to advise the patient advocacy group on medical topics and strategy: International Kidney Cancer Coalition, KIdney Cancer Association. J.B.A.G. Haanen: Financial Interests, Institutional, Advisory Board: Bristol Myers Squibb, Achilles Therapeutics, Immunocore, Gadeta, Ipsen, Merck Sharpe & Dohme, Merck Serono, Pfizer, Molecular Partners, Novartis, Roche, Sanofi, Third Rock Venture, Iovance Biotherapeutics; Financial Interests, Institutional, Advisory Board, SAB member: BioNTech, Instil Bio, PokeAcel, T-Knife; Financial Interests, Personal, Advisory Board, SAB member: Neogene Therapeutics; Financial Interests, Personal, Stocks/Shares: Neogene Therapeutics; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, BioNTech US, Merck Sharpe & Dohme, Amgen, Novartis, Asher Bio; Non-Financial Interests, Member: ASCO, AACR, SITC; Other, Editor-in-Chief IOTECH: ESMO; Other, Editorial Board ESMO Open: ESMO; Other, Editorial Board: Kidney Cancer. All other authors have declared no conflicts of interest.