Summary of Study ST002109
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
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST002109 |
| Study 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 (Part 1) |
| Study 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 |
| rachel.hill@cuanschutz.edu | |
| Phone | 303-724-5798 |
| Submit Date | 2022-03-09 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzXML |
| Analysis Type Detail | LC-MS |
| Release Date | 2022-04-04 |
| Release Version | 1 |
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Collection:
| Collection ID: | CO002187 |
| Collection Summary: | This was a multi-center, prospective, single-arm phase I/Ib safety trial. Patients eligible for treatment had to be diagnosed with non-metastatic, biopsy-proven p16-negative histology squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx, and had to be eligible and amenable to surgical resection. This study enrolled using a 3+3 model. Patients received one dose of neoadjuvant Durvalumab 1500 mg approximately 3-6 weeks before standard-of-care surgery given concurrently with the first dose of radiation (RT). The starting RT dose level was 6 Gy for 2 fractions (12 Gy total) every other day over approximately one week to sites of gross disease (Table 1) to minimize exposure to normal tissue. If toxicity developed and surgery was delayed by more than 6 weeks due to treatment toxicity (qualifying as a DLT), the radiation dose was set to be dropped per protocol for the next set of patients. If this dose was tolerated, the dose was increased to 6 Gy for 3 fractions (18 Gy total) for the next 3 patients. Patients proceeded to surgical resection approximately 3-6 weeks after radiation as recommended by the ENT surgeon. Post-operatively, pathology was reviewed at the multi-disciplinary head and neck conference, and the need for adjuvant therapy was discussed. For the first 8 patients, all patients were given adjuvant therapy based on presenting features. However, after patient 8, adjuvant therapy was dictated based on high-risk pathologic features as per the NCCN guidelines and treating physician recommendations. Adjuvant radiation included intensity-modulated radiation therapy of 60 Gy in 2 Gy once-daily fraction size once-daily fraction size (total of 30 fractions). If indicated, adjuvant systemic therapy included cisplatin or other cytotoxic chemotherapy or targeted biologics (Cetuximab) per physician discretion. All patients received adjuvant durvalumab to be initiated approximately 6-12 weeks post-surgery. It was given as 1500 mg intravenously once every 4 weeks for a maximum of 6 doses, or until progression, toxicity, or withdrawal from study. This was delivered either as monotherapy or concurrently with adjuvant radiation +/- systemic therapy for high-risk patients. Safety and toxicity evaluations were done throughout the study process. DLTs and adjustment of radiation doses were done during the neoadjuvant period. |
| Sample Type: | Blood (plasma) |
