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Publisher Correction: A phase I/Ib trial and biological correlate analysis of neoadjuvant SBRT with single-dose durvalumab in HPV-unrelated locally advanced HNSCC.

ABSTRACT:

SUBMITTER: Darragh LB

PROVIDER: S-EPMC10824658 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Publisher Correction: A phase I/Ib trial and biological correlate analysis of neoadjuvant SBRT with single-dose durvalumab in HPV-unrelated locally advanced HNSCC.

Darragh Laurel B LB Knitz Michael M MM Hu Junxiao J Clambey Eric T ET Backus Jennifer J Dumit Andrew A Samedi Von V Bubak Andrew A Greene Casey C Waxweiler Timothy T Mehrotra Sanjana S Bhatia Shilpa S Gadwa Jacob J Bickett Thomas T Piper Miles M Fakhoury Kareem K Liu Arthur A Petit Joshua J Bowles Daniel D Thaker Ashesh A Atiyeh Kimberly K Goddard Julie J Hoyer Robert R Van Bokhoven Adrie A Jordan Kimberly K Jimeno Antonio A D'Alessandro Angelo A Raben David D McDermott Jessica D JD Karam Sana D SD

Nature cancer 20240101 1

PMID: 38200246

Similar Datasets

A phase I/Ib trial and biological correlate analysis of neoadjuvant SBRT with single-dose durvalumab in HPV-unrelated locally advanced HNSCC.

Project description:Five-year survival for human papilloma virus-unrelated head and neck squamous cell carcinomas remain below 50%. We assessed the safety of administering combination hypofractionated stereotactic body radiation therapy with single-dose durvalumab (anti-PD-L1) neoadjuvantly (n = 21) ( NCT03635164 ). The primary endpoint of the study was safety, which was met. Secondary endpoints included radiographic, pathologic and objective response; locoregional control; progression-free survival; and overall survival. Among evaluable patients at an early median follow-up of 16 months (448 d or 64 weeks), overall survival was 80.1% with 95% confidence interval (95% CI) (62.0%, 100.0%), locoregional control and progression-free survival were 75.8% with 95% CI (57.5%, 99.8%), and major pathological response or complete response was 75% with 95% exact CI (51.6%, 100.0%). For patients treated with 24 Gy, 89% with 95% CI (57.1%, 100.0%) had MPR or CR. Using high-dimensional multi-omics and spatial data as well as biological correlatives, we show that responders had: (1) an increase in effector T cells; (2) a decrease in immunosuppressive cells; and (3) an increase in antigen presentation post-treatment.

| S-EPMC9701140 | biostudies-literature

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 description: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) (NCT03635164). 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, or 64 weeks), OS was 80.1% with 95% C.I. (62.0%, 100.0%), LRC and PFS were 75.8% with 95% C.I. (57.5%, 99.8%), and major pathological response (MPR) or complete response (CR) was 75% with 95% exact C.I. (51.6%, 100%). Circulating CD8/Treg ratio, CD4 effector memory T cells, and TCR repertoire at time of surgery 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.

2022-11-02 | GSE210287 | GEO

Extracellular matrix-myCAF signatures correlate with resistance to neoadjuvant aPD-L1 immune checkpoint inhibition with durvalumab + metformin in HPV+ HNSCC

Project description:In HPV-positive head and neck squamous cell carcinoma (HNSCC), early resistance to neoadjuvant durvalumab plus metformin therapy is associated with baseline enrichment of extracellular matrix–associated myofibroblastic cancer-associated fibroblasts (ECM-myCAF) within the tumor compartment. In contrast, treatment responders exhibit a distinct tumor microenvironment marked by baseline enrichment of Langerhans-like dendritic cells and post-treatment upregulation of antigen presentation pathways. These findings highlight the tumor-stroma interface as a key determinant of immunotherapy response and provide a foundation for biomarker-driven patient selection. Identifying stromal and immune signatures predictive of response to neoadjuvant aPD-L1 therapy supports future strategies targeting the tumor microenvironment to improve outcomes in HNSCC.

2025-08-29 | GSE306800 | GEO

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 description: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

| PRJNA865104 | ENA

Durvalumab and PET-Directed Chemoradiation in Locally Advanced Esophageal Adenocarcinoma: A Phase Ib/II Study.

Project description:ObjectiveTo determine the safety and efficacy of adding the anti-PD-L1 antibody durvalumab to induction FOLFOX and preoperative chemotherapy in locally advanced esophageal adenocarcinoma.BackgroundNeoadjuvant induction FOLFOX followed by positron emission tomography (PET) directed chemoradiation has demonstrated improved survival for esophageal adenocarcinoma. There is clear benefit now for the addition of immune checkpoint inhibitors both in early and advanced stage disease. Given these results we investigated the safety and efficacy of adding durvalumab to induction FOLFOX and preoperative chemoradiotherapy.MethodsPatients with locally advanced resectable esophageal/gastroesophageal junction adenocarcinoma received PET-directed chemoradiation with durvalumab before esophagectomy. Patients who had R0 resections received adjuvant durvalumab 1500 mg every 4 weeks for 6 treatments. The primary endpoint of the study was pathologic complete response.ResultsWe enrolled 36 patients, 33 of whom completed all preoperative treatment and underwent surgery. Preoperative treatment was well tolerated, with no delays to surgery nor new safety signals. Pathologic complete response was identified in 8 [22% (1-sided 90% lower bound: 13.3%)] patients with major pathologic response in 22 [61% (1-sided 90% lower bound: 50%)] patients. Twelve and 24-month overall survival was 92% and 85%, respectively.ConclusionsThe addition of durvalumab to induction FOLFOX and PET-directed chemoradiotherapy before surgery is safe, with a high rate of pathologic response, as well as encouraging survival data.

| S-EPMC11065504 | biostudies-literature

Publisher Correction: Neoadjuvant adebrelimab in locally advanced resectable esophageal squamous cell carcinoma: a phase 1b trial.

Project description: Not available

| S-EPMC10504064 | biostudies-literature

Extracellular matrix-myCAF signatures correlate with resistance to neoadjuvant aPD-L1 immune checkpoint inhibition with durvalumab + metformin in HPV+ HNSCC

Project description:Extracellular matrix-myCAF signatures correlate with resistance to neoadjuvant aPD-L1 immune checkpoint inhibition with durvalumab + metformin in HPV+ HNSCC

| PRJNA1312367 | ENA

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)

Project description: Not available

| ST002110 | MetabolomicsWorkbench

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)

Project description: Not available

| ST002109 | MetabolomicsWorkbench

Safety and efficacy of single cycle induction treatment with cisplatin/docetaxel/ durvalumab/tremelimumab in locally advanced HNSCC: first results of CheckRad-CD8.

Project description:To determine safety and efficacy of single cycle induction treatment with cisplatin/docetaxel and durvalumab/tremelimumab in stage III-IVB head and neck cancer. Patients received a single cycle of cisplatin 30 mg/m² on days 1-3 and docetaxel 75 mg/m² on day 1 combined with durvalumab 1500 mg fix dose on day 5 and tremelimumab 75 mg fix dose on day 5. Patients with pathologic complete response (pCR) in the rebiopsy after induction treatment or at least 20% increase of intratumoral CD8+ cell density in the rebiopsy compared with baseline entered radioimmunotherapy with concomitant durvalumab/tremelimumab. The objective of this interim analysis was to analyze safety and efficacy of the chemoimmunotherapy-induction treatment before radioimmunotherapy. A total of 57 patients were enrolled, 56 were treated. Median pretreatment intratumoral CD8+ cell density was 342 cells/mm². After induction treatment, 27 patients (48%) had a pCR in the rebiopsy and further 25 patients (45%) had a relevant increase of intratumoral CD8+ cells (median increase by a factor of 3.0). Adverse event (AE) grade 3-4 appeared in 38 patients (68%) and mainly consisted of leukopenia (43%) and infections (29%). Six patients (11%) developed grade 3-4 immune-related AE. Univariate analysis computed p16 positivity, programmed death ligand 1 immune cell area and intratumoral CD8+ cell density as predictors of pCR. On multivariable analysis, intratumoral CD8+ cell density predicted pCR independently (OR 1.0012 per cell/mm², 95% CI 1.0001 to 1.0022, p=0.016). In peripheral blood CD8+ cells, the coexpression of programmed death protein 1 significantly increased especially in patients with pCR. Single cycle induction treatment with cisplatin/docetaxel and durvalumab/tremelimumab is feasible and achieves a high biopsy-proven pCR rate.

| S-EPMC7539609 | biostudies-literature

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