Summary of project PR001336
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001336. The data can be accessed directly via it's Project DOI: 10.21228/M81D70 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR001336 |
| Project DOI: | doi: 10.21228/M81D70 |
| Project Title: | Towards a mechanistic understanding of patient response to neoadjuvant SBRT with anti-PDL1 in human HPV-unrelated locally advanced HNSCC: Phase I/Ib trial results |
| Project Summary: | Five-year survival for HPV-unrelated head and neck squamous cell carcinomas (HNSCC) remains below 50%. We assessed the safety of administering combination hypofractionated stereotactic body radiation therapy (SBRT) with anti-PDL-1 neoadjuvantly followed by adjuvant anti-PDL-1 with standard of care therapy (n=21). The primary endpoint of the study was safety, which was met. Secondary endpoints included radiographic, pathologic, and objective response, locoregional control (LRC), progression-free survival (PFS), and overall survival (OS). Among evaluable patients at early median follow-up of 16 months (448 days), OS was 83.3%, LRC and PFS were 83.3%, and major pathological response (MPR) or complete response (CR) was 75%. Circulating CD8/Treg ratio, CD4 effector memory T cells, and TCR repertoire emerged as biologic correlates of response to therapy. Using high-dimensional multi-omics and spatial data as well as biological correlatives pre- and post-treatment, three major changes were noted in responders within the tumor microenvironment (TME) (and within the blood) post-treatment: 1) an increase in effector T cells; 2) a decrease in immunosuppressive cells; and 3) an increase in antigen presentation. Non-responders appeared to fail due to a lack of one of these three identified steps needed for priming and maintaining activation of T cells. Multiple correlates for response, along with subsets of non-responders that may benefit from additional or alternative immunotherapies, were identified. This treatment is being tested in an ongoing phase II trial with a similar design, where we hope to confirm and expand on our understanding of the mechanisms underlying resistance to therapy. |
| Institute: | University of Colorado Denver |
| Last Name: | Culp-Hill |
| First Name: | Rachel |
| Address: | 12801 E 17th Ave L18-9403D, Aurora, Colorado, 80045, USA |
| Email: | rachel.hill@cuanschutz.edu |
| Phone: | 303-724-5798 |
Summary of all studies in project PR001336
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST002109 | Towards a mechanistic understanding of patient response to neoadjuvant SBRT with anti-PDL1 in human HPV-unrelated locally advanced HNSCC: Phase I/Ib trial results (Part 1) | Homo sapiens | University of Colorado Denver | MS | 2022-04-04 | 1 | 41 | Uploaded data (708.7M)* |
| ST002110 | Towards a mechanistic understanding of patient response to neoadjuvant SBRT with anti-PDL1 in human HPV-unrelated locally advanced HNSCC: Phase I/Ib trial results (Part 2) | Homo sapiens | University of Colorado Denver | MS | 2022-04-04 | 1 | 40 | Uploaded data (542.2M)* |
