American Association for Cancer Research
ccr-23-1807_supplementary_figure_s3_suppfs3.pdf (235.24 kB)

Supplementary Figure S3 from Phase II Trial of Nivolumab in Metastatic Rare Cancer with dMMR or MSI-H and Relation with Immune Phenotypic Analysis (the ROCK Trial)

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journal contribution
posted on 2023-12-15, 08:42 authored by Hitomi S. Okuma, Keisuke Watanabe, Kenji Tsuchihashi, Ryunosuke Machida, Ryo Sadachi, Akihiro Hirakawa, Hiroshi Ariyama, Masashi Kanai, Masahisa Kamikura, Kenta Anjo, Akari Hiramitsu, Shigeki Sekine, Natsuko Okita, Hiroyuki Mano, Hiroyoshi Nishikawa, Kenichi Nakamura, Kan Yonemori

Supplementary Figure S3: Gating strategy for immune phenotyping analysis.



Mismatch repair deficiency (dMMR)/microsatellite instability-high (MSI-H) are positive predictive markers for immune checkpoint inhibitors. However, data on the activity of nivolumab in advanced dMMR/MSI-H rare cancers and more accurate biomarkers are worth exploring. We conducted a multicenter phase II, open-label, single-arm clinical trial to explore the effectiveness and safety of nivolumab monotherapy in patients with advanced rare cancers with dMMR/MSI-H, in parallel with immune phenotype analysis, to explore new biomarkers. A Bayesian adaptive design was applied. Characterization of peripheral blood mononuclear cells (PBMC) was characterized by multicolor flow cytometric analysis and CyTOF using samples collected before and after the intervention. The dMMR was identified by the complete loss of MLH1/MSH2/MSH6/PMS2. From May 2018 to March 2021, 242 patients were screened, and 11 patients were enrolled, of whom 10 were included in the full analysis. Median follow-up was 24.7 months (interquartile range, 12.4–31.5). Objective response rate was 60% [95% confidence interval (CI), 26.2–87.8] by central assessment and 70% (95% CI, 34.8–93.3) by local investigators. Median progression-free survival was 10.1 months (95% CI, 0.9–11.1). No treatment-related adverse events of grade 3 or higher were observed. Patients with a tumor mutation burden of ≥10/Mb showed a 100% response rate (95% CI, 47.8–100). Responders had increased T-bet+ PD-1+ CD4+ T cells in PBMC compared with nonresponders (P < 0.05). The trial met its primary endpoint with nivolumab, demonstrating clinical benefit in advanced dMMR/MSI-H rare solid cancers. Besides, the proportion of T-bet+ PD-1+ CD4+ T-cells may serve as a novel predictive biomarker.