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Circulating tumor DNA, pathological and immunologic responses to neoadjuvant nivolumab or nivolumab plus relatlimab and chemoradiotherapy in resectable esophageal/gastroesophageal junction cancer

ABSTRACT: Gastroesophageal tumor kinetics during immune checkpoint inhibition (ICI) remain poorly understood. We report a phase II trial that evaluated neoadjuvant nivolumab (arm A) or nivolumab-relatlimab (arm B) in combination with chemoradiotherapy in 32 patients with resectable gastroesophageal cancer together with an in-depth evaluation of pathological, molecular and functional immune responses (NCT03044613). Patients with undetectable circulating tumor DNA (ctDNA) post-ICI induction, pre- and post-operatively had a significantly longer RFS and OS. Cell-free tumor load contraction was reflective of neoantigen-specific T-cell responses. Our findings highlight tumor kinetics during ICI that may open a therapeutic window for future intervention.

PROVIDER: EGAS00001007299 | EGA |

REPOSITORIES: EGA

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Immunomodulatory response to neoadjuvant nivolumab in non-metastatic clear cell renal cell carcinoma

Project description:Novel perioperative strategies are needed to reduce recurrence rates in patients undergoing nephrectomy for high-risk, non-metastatic clear cell renal cell carcinoma (ccRCC). We conducted a prospective, phase I trial of neoadjuvant nivolumab prior to nephrectomy in 15 evaluable patients with non-metastatic ccRCC. We leveraged tissue from that cohort to elucidate the effects of PD-1 inhibition on immune cell populations in ccRCC and correlate the evolving immune milieu with anti-PD-1 response. We found that nivolumab durably induces a pro-inflammatory state within the primary tumor, and baseline immune infiltration within the primary tumor correlates with nivolumab responsiveness. Nivolumab increases CTLA-4 expression in the primary tumor, and subsequent nephrectomy increases circulating concentrations of sPD-L1, sPD-L3 (sB7-H3), and s4-1BB. These findings form the basis to consider neoadjuvant immune checkpoint inhibition (ICI) for high-risk ccRCC while the tumor remains in situ and provide the rationale for perioperative strategies of novel ICI combinations.

2023-12-18 | GSE245372 | GEO

Biopsies from metastatic Clear Cell Renal Carcinoma before or after treatment with nivolumab

Project description:Tumor core needle biopsies from kidney or metastatic sites obtained at trial enrollment i.e. Screen and/or at Cycle 2 Day 8 (i.e.Week 4) from metastatic clear cell RCC patients treated with 0.2mpk, 3mpk or 10mpk (as 2nd or further line of therapy; Arms A,B,C) or 10mpk (as first line therapy; Arm D) of nivolumab (BMS-936558,MDX-1106) on Bristol-Myers Squibb clinical trial protocol CA209-009.

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2016-05-15 | E-MTAB-3219 | biostudies-arrayexpress

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2023-07-10 | GSE216297 | GEO

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2023-12-31 | GSE243572 | GEO

Next Generation Sequencing Facilitates Quantitative Analysis of tumor samples from HCC patients receiving Nivolumab.

Project description:To identify critical tumor-secreting factors that may contribute to immunotherapy efficacy against HCC, we subjected tumor samples from 10 HCC patients to whole-transcriptome sequencing, and categorized the patients into two groups according to clinical response to nivolumab. We then performed gene expression profiling analysis using data obtained from RNA-seq of Nivolumab reponders and non-reponsers.

2023-12-06 | GSE215011 | GEO

Expression data from patients with HCC receiving Nivolumab

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Sitravatinib Plus Nivolumab in Patients Undergoing Nephrectomy for Locally Advanced Clear Cell Renal Cell Carcinoma

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Sitravatinib in combination with nivolumab plus ipilimumab in patients with advanced clear cell renal cell carcinoma: a phase 1 trial

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