Abstract 4138
Background
ADATPeR is the first prospective study evaluating the role of anti-PD1 agents in the neoadjuvant setting prior to cytoreductive nephrectomy in treatment-naïve patients with metastatic clear cell renal cell carcinoma (mccRCC). We performed multi-omic analyses to resolve spatial heterogeneity and temporal dynamics in putative biomarkers of response to anti-PD1 blockade.
Methods
In a single center study, patients received nivolumab (3mg/kg every 2 weeks) pre- and post-operatively until progressive disease (PD). Primary endpoint was safety, secondary endpoints were response evaluation and exploratory biomarker analysis. Multiregion tumour biopsies were obtained at baseline, on-treatment (week 9) and at PD. Whole-exome sequencing was performed to infer somatic mutations and predict candidate neoantigens (NAs). Tumour immune microenvironment was evaluated using a RNA-seq-derived immune signature and by stromal and intraepithelial tumour infiltrating lymphocytes (TILs) assessments.
Results
15 patients were treated. At median follow-up of 12.5 months(m), nivolumab had an acceptable side-effect profile. Overall response rate was 37%. Preliminary transcriptome analyses of pre-treatment biopsies (33 samples from 14 patients; up to 4 regions per case) revealed enrichment for primary-resistance (defined as PD within 2m; n = 4) with immune ‘cold’ tumours, distinct from ’hot’ tumours. Histologic TILs scoring showed concordant immune phenotypic clusters. Primary-resistant cases demonstrated 0% on-treatment stromal- and IE-TILs (2 evaluable patients). In contrast, we observed heavy on-treatment stromal TILs (70-90%) and intraepithelial TILs (30-90%) across 7 regions at nephrectomy in an exceptional responder receiving ongoing treatment (>24 cycles).
Conclusions
ADATPeR is the first neoadjuvant immune checkpoint inhibitor study pre-cytoreductive nephrectomy, and incorporated multi-omic analyses of putative biomarkers. Baseline immune gene expression signature is distinct in responders compared with non-responders. On-treatment intraepithelial TILs were prominent in those deriving durable clinical benefit. Integrative analyses are ongoing.
Clinical trial identification
NCT02446860.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Bristol-Myers Squibb; The National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research; Cancer Research UK (CRUK).
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
4145 - Diagnosis, Management, and Burden of Renal Cell Carcinomas: Results from a Global Patient Survey in 43 countries
Presenter: Rachel Giles
Session: Poster Discussion – Genitourinary tumours, non-prostate
Resources:
Abstract
Poster Discussion – Genitourinary tumours, non-prostate - Invited Discussant 904PD, 905PD and 906PD
Presenter: Joaquim Bellmunt
Session: Poster Discussion – Genitourinary tumours, non-prostate
Resources:
Slides
Webcast
Poster Discussion – Genitourinary tumours, non-prostate - Invited Discussant 907PD, 908PD, 909PD and 910PD
Presenter: Guillermo A. De Velasco Oria de Rueda
Session: Poster Discussion – Genitourinary tumours, non-prostate
Resources:
Slides
Poster Discussion – Genitourinary tumours, non-prostate - Invited Discussant 911PD and 912PD
Presenter: Viktor Gruenwald
Session: Poster Discussion – Genitourinary tumours, non-prostate
Resources:
Slides
Webcast
Poster Discussion – Genitourinary tumours, non-prostate - Invited Discussant 913PD, 914PD and 915PD
Presenter: Christian Kollmannsberger
Session: Poster Discussion – Genitourinary tumours, non-prostate
Resources:
Slides
Webcast