Abstract 977TiP
Background
Gut microbiome has been associated with response and toxicity to anti-cancer therapies across multiple tumor types, including head and neck cancer. ROMA LA-OPSCC-001 (NCT03759730) was the first study to prospectively characterize the oral and gut microbiome of pts with LA-OPSCC treated with chemoradiotherapy (CRT). We previously reported CRT reduced the diversity and increased the number of pathogenic taxa of the oral microbiome, but did not impact on gut microbiome’s composition (Oliva M, et al. ASCO 2019). While selective manipulation of the gut microbiome to augment antitumor immune responses is being evaluated in pts with metastatic disease, its feasibility in the LA setting and in the context of CRT has yet to be explored. Microbial Ecosystem Therapeutics (MET-4) is an orally-administered consortium of immune-favorable intestinal bacteria isolated from healthy donor stool samples. To our knowledge, ROMA LA-OPSCC-2 (NCT03838601) is the first study to evaluate the modulation of the gut microbiome in LA-OPSCC pts treated with radical CRT.
Trial design
This is a single-centre study involving a prospective cohort of 30 pts with newly diagnosed LA-OPSCC to be treated with standard of care CRT (7 weeks of radiotherapy plus cisplatin three-weekly x 3 doses or weekly x 7 doses) at Princess Margaret Cancer Centre. MET-4 is administered orally daily until week 4 of CRT (as oral mucositis may impact compliance beyond this point), or unacceptable toxicity. The primary endpoint of the study is to evaluate the relative abundance of MET-4 species in stool samples (colonization). Tumor swabs and fresh stool samples are collected at several timepoints to determine oral and gut taxonomic composition using 16s rRNA and shotgun metagenomics. Serial blood sampling for flow cytometry/CyTOF will be performed to correlate changes in immune cell subsets. Exploratory analyses include blood and stool metabolomics as well as correlation with radiomic imaging analyses. Subjects unable to swallow oral medications or absorption problems are excluded. This is a signal-finding study focusing on correlative studies and hypothesis generation. As of May 16th, 14 pts have been enrolled.
Clinical trial identification
NCT03838601.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Nubiyota.
Disclosure
G.A. Watson: Honoraria (self): Pfizer; Travel/Accommodation/Expenses: AbbVie; Travel/Accommodation/Expenses: BMS. M. Oliva: Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Mirati Therapeutics; Research grant/Funding (institution): Mirati Therapeutics; Travel/Accommodation/Expenses: MSD Oncology; Travel/Accommodation/Expenses: Merck. A.R. Hansen: Advisory/Consultancy: Genentech/Roche; Advisory/Consultancy: Merck; Advisory/Consultancy: GlaxoSmithKline; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Novartis; Advisory/Consultancy: Boston Biomedical; Advisory/Consultancy: Boehringer Ingelheim; Honoraria (institution): Merck; Honoraria (institution): AstraZeneca/MedImmune; Honoraria (institution): Pfizer; Honoraria (institution): GlaxoSmithKline; Honoraria (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Karyopharm Therapeutics; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): GlaxoSmithKline; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Roche/Genentech; Research grant/Funding (institution): Janssen. L.L. Siu: Advisory/Consultancy: Merck; Advisory/Consultancy: AstraZeneca/MedImmune; Advisory/Consultancy: MorphoSys; Advisory/Consultancy: Roche; Advisory/Consultancy: Loxo; Advisory/Consultancy: Voronoi; Advisory/Consultancy: Oncorus; Advisory/Consultancy: Symphogen; Advisory/Consultancy: Mirati Therapeutics; Advisory/Consultancy: GlaxoSmithKline; Advisory/Consultancy: Seattle Genetics; Research grant/Funding (institution): AVID Radiopharmaceuticals; Advisory/Consultancy: Arvinos; Advisory/Consultancy: Navire; Leadership role, And advisory/consultancy: Treadwell Therapeutics; Shareholder/Stockholder/Stock options: Agios; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Genentech/Roche; Research grant/Funding (institution): GlaxoSmithKline; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): AstraZeneca/MedImmune; Research grant/Funding (institution): Astellas; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Shattuck Labs; Research grant/Funding (institution): Intensity Therapeutics; Research grant/Funding (institution): Karyopharm Therapeutics; Research grant/Funding (institution): Symphogen. A. Spreafico: Advisory/Consultancy: Merck; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Novartis; Advisory/Consultancy: Oncorus; Advisory/Consultancy: Janssen; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Symphogen; Research grant/Funding (institution): AstraZeneca/MedImmune; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Surface Oncology; Research grant/Funding (institution): Northern Biologics; Research grant/Funding (institution): Janssen; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Regeneron; Research grant/Funding (institution): Alkermes; Research grant/Funding (institution): Array Biopharma. All other authors have declared no conflicts of interest.