Study protocol of a randomized controlled phase II trial comparing nivolumab, ipilimumab plus radiotherapy versus nivolumab plus ipilimumab for advanced or recurrent esophageal cancer - Japan Clinical Oncology Group study JCOG2311 (ART NOUVEAU)

Sep 30, 2026

Upload by pop out

Immunogenic cell death induced by radiotherapy can strengthen systemic antitumor activity of immune checkpoint inhibitors, motivating trials that integrate radiotherapy to reduce early treatment failure. This randomized phase II study (initiated November 2024) compares radiotherapy plus nivolumab and ipilimumab versus nivolumab plus ipilimumab alone in advanced or recurrent esophageal squamous cell carcinoma, with progression-free survival as the primary endpoint and overall survival, response, response duration, and adverse events as secondary endpoints. The design targets 74 enrolled patients.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages7

Reading Time18 min

AccessFree to download

Background

Rationale and current standards

Methods

Trial design and endpoints

Sample size and study procedures

Discussion

Safety, efficacy, and translational aims

Trial registration

Registration details and registry entry

Sakanaka etal. BMC Cancer (2026) 26:34 BMC Cancer [https://doi.org/10.1186/s12885-025-15403-2](https://doi.org/10.1186/s12885-025-15403-2) STUDY PROTOCOL Open Access Study protocol of a randomized controlled phase II trial comparing nivolumab, ipilimumab plus radiotherapy versus nivolumab plus ipilimumab for advanced or recurrent esophageal cancer: Japan Clinical Oncology Group study JCOG2311 (ART NOUVEAU) Katsuyuki Sakanaka 1*, Keita Sasaki2, Takahiro Tsushima3, Ryunosuke Machida2, Yoichi Hamai4, Akinori Watanabe5, Kota Kawabata2, Satoru Matsuda6, Ken Kato7, Haruhiko Fukuda2, Hiroya Takeuchi8 and Japan Esophageal Oncology Group of the Japan Clinical Oncology Group Abstract Background The immunogenic cell death induced by radiotherapy (RT) has been demonstrated to enhance the systemic antitumor effect of immune checkpoint inhibitors (ICIs) . The incorporation of RT into ICIs has the potential to mitigate the occurrence of early treatment failure, particularly with dual ICI combination, in patients with advanced or recurrent esophageal cancer. Methods This randomized phase II trial, initiated in November 2024, aims to explore the superiority of the combination of RT with nivol umab plus ipilimumab over nivolumab plus ipilimumab alone in patients with advanced or recurrent esophageal squamous cell carcinoma. The primary endpoint is progression-free survival, while the secondary endpoints include overall survival, response rate, duration of response, and adverse events. We assumed a 6-month PFS of 35% in the nivolumab plus ipilimumab alone arm and expected a 15% increase in the 6-month PFS for the RT with nivol umab plus ipilimumab arm (HR, 0 . 66) . The total required sample size was calculated to be 70 (35 per arm) to achieve a desired power of 80% with an overall one-sided alpha of 20%, an accrual period of 2.5 years, and a follow-up period of 1 year. A total of 74 patients will be enrolled from 41 institutions in Japan. An ancillary study analyzes cytokine profiles and phenotypic characteristics in peripheral blood mononuclear cells during treatment with the protocol. *Correspondence: Katsuyuki Sakanaka [sakanaka@kuhp.kyoto-u.ac.jp](sakanaka@kuhp.kyoto-u.ac.jp) Full list of author information is available at the end of the article © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creati](http://creati)[vecommons.org/l](vecommons.org/l)icenses/by-nc-nd/4.0/. Sakanaka et al. BMC Cancer (2026) 26:34 Page 2 of 7 Discussion The objective of this trial is to assess the safety and efficacy of RT in combination with dual ICIs in reducing early treatment failure and improving outcomes with translational research. Findings from this trial will inform a future phase III trial in this patient population. Trial registration This trial has been registered on November 5th, 2024, in the Japan Registry of Clinical Trials as jRCT1031240461 ( [https://jrct. mhlw.go.jp/en-latest-detail/jRCT1031240461](https://jrct. mhlw.go.jp/en-latest-detail/jRCT1031240461)) . Keywords Esophageal

FAQs

What is the main goal of this randomized phase II trial?

To evaluate whether adding radiotherapy to nivolumab plus ipilimumab improves outcomes and reduces early treatment failure in patients with advanced or recurrent esophageal squamous cell carcinoma.

What are the primary and secondary endpoints?

Progression-free survival is the primary endpoint. Secondary endpoints include overall survival, response rate, duration of response, and adverse events.

How many patients are planned and how is the sample size determined?

A total of 74 patients will be enrolled from 41 institutions in Japan. The required sample size was calculated as 70 (35 per arm) to achieve 80% power with a one-sided alpha of 20%, assuming a 35% 6-month PFS in the control arm and a 15% absolute increase with radiotherapy.

Sep 30, 2026

Upload by pop out