Personalis has joined with Duke University and Olink Proteomics to form a research collaboration to study the effects of immunotherapy on advanced gastroesophageal cancer. Specifically, the collaboration will focus on identifying composite biomarkers—those that integrate multiple biological entities into a single readout—to help guide therapeutic decision making.

Personalis was founded in 2011 as a Stanford University spin-out by Russ Altman, MD, PhD, Euan Ashley, MD, PhD, Atul Butte, MD, PhD, and Michael Snyder, PhD. The platform of the cancer genomics company, ImmunoID NeXT Platform, will be used for characterization of tumor genomic and transcriptomic alterations, as well as differences between responders and non-responders.

Additionally, Personalis’ NeXT Personal assay will be used to analyze circulating tumor DNA (ctDNA) collected from patients in order to profile and accurately track molecular residual disease (MRD) over the course of therapy. NeXT Personal is a tumor-informed liquid biopsy assay designed to detect and quantify MRD and recurrence in patients previously diagnosed with cancer. The assay is designed to deliver MRD sensitivity down to the one part-per-million range.

Olink Explore panels will be used to analyze plasma samples and tumor tissues from metastatic gastroesophageal cancer patients being treated with anti-PD1 and anti-PD1/chemotherapy. The proteomics company, with headquarters in Uppsala, Sweden, was founded in 2016.

“Biomarkers that predict and characterize tumor responses to anti-PDL1/PD1 therapy remain poorly understood, largely due to the complex and multifaceted interactions between the tumor and immune system,” said Andrew Nixon, PhD, director of the Phase I Biomarker Laboratory, Duke University School of Medicine. “Through comprehensive plasma and tumor immune profiling, we aim to clarify the interconnected roles of tumor genomics and proteomics, as well as the development of composite biomarkers to clinically predict and follow immunotherapy response.”

Gastroesophageal cancer is the fourth most common cancer worldwide, with nearly 50% of patients having developed unresectable or metastatic disease at the time of diagnosis. Chemotherapy is currently the standard of care for patients with this type of advanced disease; however, its effectiveness is often diminished as many patients develop therapeutic resistance. When this happens, the median overall survival for patients drops to less than nine months.

Fortunately, pembrolizumab, an immunotherapeutic targeting PDL1/PD1, has been approved by the FDA for use in patients with chemorefractory gastroesophageal cancer. The effectiveness of this biologic has inspired significant interest in applying it as a first-line, standard-of-care treatment for patients with advanced disease.

To that end, the goal of the collaborative study is to characterize key tumor and immunological responses to pembrolizumab, and in so doing, shine light on the potential mechanisms that lead to either sensitivity or resistance to immunotherapeutics in gastroesophageal cancer. By detailing how tumors respond to treatment at the genomic, transcriptomic, and proteomic levels, the team aims to uncover biomarkers that may help physicians predict tumor responses to pembrolizumab and adjust treatment strategies accordingly.

“This study has the potential to identify the mechanisms of immune resistance in metastatic gastroesophageal cancer, which may enable strategies to optimize response rates to existing immunotherapies and develop novel therapeutics that overcome resistance,” said Marijana Rucevic, PhD, senior scientific director, Olink Proteomics.

“We believe the clinical management of cancer can substantially improve with early determination of patient response and by accurately informing changes to treatment regimens,” said Richard Chen, MD, chief medical officer and senior vice president of R&D at Personalis. “Such determinations offer the potential to avoid unnecessary toxicities and increase survival.”

 

Olink’s Proximity Extension Assay (PEA) technology