Abstract 4779
Background
Despite the application of PD-1 inhibitors in clinical practice in SCCHN, only a fraction of patients shows durable responses to monotherapy. Numerous combinatorial strategies have been utilized to attempt to augment immunotherapy efficacy. While dysregulated tumour metabolism (TM) is a critical feature of the tumour microenvironment (TME) and impacts immune function within the TME, much remains to be done to bridge these areas and explore therapeutic opportunities. Recent murine xenograft and clinical translational data suggests that metformin alters TM, and preclinical data suggests possible potentiation of PD-1 axis inhibition by metformin.
Methods
This is a single-center, randomized trial for patients with all stages of resectable SCCHN, with planned enrollment of 38 patients. Part 1, which has been completed, was a safety run-in with 6 patients treated with metformin (met) + durvalumab (durva) for safety evaluation. Part 2 will enroll 32 additional patients with a 3:1 randomization to treatment arm A (met 1000 mg BID Day 1-31 + durva 1500 mg IV x 1 on Day 3) and treatment arm B (durva 1500 mg IV x 1). Tumor and blood will be collected pre and post treatment with analysis of immune cell composition. The primary endpoint is the combined effect of metformin and durvalumab on the immune TME, specifically with respect to alterations in T cell and macrophage polarization. Secondary endpoints include safety and tolerability, alterations in immunohistochemical markers of the TME, transcriptome and circulating DNA analysis, and objective response rate.
Results
Six patients were enrolled in Part 1. All were males with a mean age of 65.7 ± 6.8 years. All patients had grade 1 adverse events (AE) consisting mainly of gastrointestinal (diarrhea, nausea, or abdominal cramps) and constitutional (anorexia, fatigue, or sleep disturbance) symptoms. No patient experienced AE > = grade 2. All patients were able to proceed to surgery without unanticipated delays.
Conclusions
The combination of met and durva was safe in the first cohort of patients. Enrollment for Part 2 is ongoing.
Clinical trial identification
NCT03618654.
Editorial acknowledgement
Legal entity responsible for the study
Sidney Kimmel Cancer Center at Thomas Jefferson University Sidney Kimmel Cancer Center at Thomas Jefferson University Sidney Kimmel Cancer Center at Thomas Jefferson University Sidney Kimmel Cancer Center at Thomas Jefferson University.
Funding
Sidney Kimmel Cancer Center at Thomas Jefferson University.
Disclosure
J.M. Johnson: Research grant / Funding (self): Bristol-Myers Squibb. A. Argiris: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Merck Serono; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy: Roche; Advisory / Consultancy: Debiopharm Group; Advisory / Consultancy: Aspyrian Therapeutics; Research grant / Funding (self): Genentech/Roche. A. Luginbuhl: Research grant / Funding (self): Bristol-Myers Squibb. R. Zinner: Research grant / Funding (institution), Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time employment, An Immediate Family Member: Merck; Research grant / Funding (institution), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Travel / Accommodation / Expenses: Lilly. U. Rodeck: Shareholder / Stockholder / Stock options: Akriveia Therapeutics; Research grant / Funding (self): Advaxis; Licensing / Royalties: Several Patents. J.M. Curry: Research grant / Funding (self): AstraZeneca. All other authors have declared no conflicts of interest.
Resources from the same session
5544 - Evaluation of a radiomic signature of CD8 cells in patients treated with immunotherapy-radiotherapy in three clinical trials.
Presenter: Roger Sun
Session: Poster Display session 3
Resources:
Abstract
1117 - Biomarkers predictive of overall survival in advanced cancer patients treated with a peptide-based cancer vaccine.
Presenter: Shigetaka Suekane
Session: Poster Display session 3
Resources:
Abstract
1922 - Expression of PD-L1 in plasma exosomes of NSCLC patients and its associations with PD-L1 expression of corresponding tumor tissues
Presenter: Shaorong Yu
Session: Poster Display session 3
Resources:
Abstract
5495 - Patient’s perspective on digital biomarkers in advanced urologic malignancies
Presenter: Severin Rodler
Session: Poster Display session 3
Resources:
Abstract
3166 - A comprehensive Pan-cancer study of FGFR Aberrations in Chinese cancer patients
Presenter: Yang Gao
Session: Poster Display session 3
Resources:
Abstract
3277 - A Systemic Inflammation Response Index (SIRI) correlates with survival and could be a Predictive Factor for mFOLFIRINOX in Metastatic Pancreatic Cancer (PC)
Presenter: Vilma Pacheco-Barcia
Session: Poster Display session 3
Resources:
Abstract
2680 - Circulating biomarkers and risk of immune-related adverse events (irAEs) in patients (pts) with advanced Non-small cell lung cancer (aNSCLC) and metastatic melanoma (mMel)
Presenter: Alberto Pavan
Session: Poster Display session 3
Resources:
Abstract
4066 - Breast cancer in young women of Kazakh population depending on germline mutations: results of next-generation sequencing
Presenter: Dilyara Kaidarova
Session: Poster Display session 3
Resources:
Abstract
5514 - Discovery of an ImmunoTranscriptomics signature in blood for early colorectal cancer detection
Presenter: Paolo Angelino
Session: Poster Display session 3
Resources:
Abstract
1595 - Serum Netrin-1 as a Biomarker for Colorectal Cancer Detection
Presenter: Jinzhou Zhu
Session: Poster Display session 3
Resources:
Abstract