Immunoscore® to select patients in the POCHI trial, a phase II multicenter trial testing immunotherapy with chemotherapy and bevacizumab in metastatic colorectal cancer

Marseille, France, September 10, 2020 - HalioDx SAS, the immuno-oncology diagnostic company, today announced that it has entered into a Collaboration Agreement with the FFCD, the French Cooperative Group dedicated exclusively to digestive oncology, on the Phase II multicenter POCHI trial (FFCD1703 - NCT04262687) in which immune response at the tumor site will be used to inform patient eligibility to participiate in the POCHI trial. The objective of the trial is to evaluate the efficacy of pembrolizumab in combnation with XELOX (capecitabine plus oxaliplatin) and bevacizumab as first line treatment of microsatellite stable (MSS) / proficient mismatch repair system (pMMR) metastatic colorectal cancer (mCRC) with high immune infiltrate.

Immune Checkpoint Inhibitors (ICIs) have demonstrated high efficacy in mCRC with microsatellite instability (MSI) / deficient mismatch repair system (dMMR) but remain ineffective alone in MSS/ pMMR tumors. MSS/pMMR tumors presenting a high immune infiltrate as assessed by Immunoscore® could be sensitive to ICI therapy. The POCHI trial will prospectively enroll about 400 patients with the goal of testing the combination on 55 patients with an MSS/pMMR mCRC with high immune response (≈15%).

David Tougeron, MD, PhD at Poitiers University Hospital, Principal Investigator of the POCHI trial comments: “The POCHI study is crucial to determine whether tumor immune response assessment can help identifying MSS/pMMR mCRC patients eligible for ICI in combination with chemotherapy plus anti-angiogenic. We believe that this study will lead to a phase III trial to evaluate ICI combination in patients with an MSS/pMMR mCRC with a high immune score.”

Vincent FERT, CEO of HalioDx comments: “Immunoscore® offers a unique opportunity to extend the number of patients with mCRC potentially candidates to immunotherapy, and we are delighted to take part in this effort. Aside the now well demonstrated performances and clinical utility of Immunoscore® in localized colon cancer and notably its predictive performance for the duration of adjuvant chemotherapy, we believe that Immunoscore®, holds a significant potential for predicting immunotherapy response by gauging the immune response to tumor”, he added. 

About MSS/pMMR mCRC and the POCHI trial

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second in terms of mortality. Over 1.8 million of CRC cases and 881.000 CRC-related deaths were estimated to occur in 2018 in the world. Despite significant improvements in CRC treatment, the prognosis of patients with metastatic CRC (mCRC) remains poor, with a median overall survival (OS) of approximately 30 months. For this reason, novel and more effective therapeutic strategies are necessary for metastatic disease.

About 85% of cases of non-metastatic CRC are related to chromosomal instability and have a proficient DNA Mismatch-Repair system (pMMR) which are also called CRC with microsatellite stability (MSS). Other CRC, i.e. 15%, present "microsatellite instability" (MSI) with deficient DNA Mismatch-Repair system (dMMR). These latter are characterized by generation of many neo-antigens due to genomic instability, which result in a high anti-tumor immune response and a high peri- and/or intra-tumor lymphocyte infiltration (TIL). Investigators recently showed, with a prospectively validated immune score, that ≈15% of MSS/pMMR CRC are also highly immune infiltrated.

Pembrolizumab is an anti-PD1 monoclonal antibody recently approved in many cancers. Anti-PD1 antibodies have recently been reported as being very effective in patients with MSI/dMMR metastatic CRC (mCRC) whereas MSS/pMMR mCRC did not benefit from anti-PD1 antibodies alone. However, it is possible that 15% of MSS/pMMR mCRC with a high immune infiltrate in the tumor may be a subgroup of MSS/pMMR mCRC sensitive to ICI in combination with immunogenic drugs like oxaliplatin and anti-angiogenic.

Investigators formulated the hypothesis that patients with an MSS/pMMR CRC and a high immune infiltrate could be sensitive to ICI combination. Therefore, blocks of resected primary tumor will be collected and analyzed prospectively. Tumors will then be classified as having a "high" or "low" immune response according to the density and type of lymphocyte infiltrate. Only patients with a high immune response will be eligible for the POCHI trial. The clinical hypotheses are to increase rate of patients alive and without radiological and/or clinical progression at 10 months (PFS at 10 months) from 50% to 70%.

If investigators identify an immune score clinically relevant to predict sensitivity to ICI in MSS/pMMR mCRC, a randomized phase III trial could be considered to compare chemotherapy and anti-angiogenic versus chemotherapy and anti-angiogenic plus pembrolizumab in patients with an MSS/pMMR mCRC and a high immune score.

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About Immunoscore®

Immunoscore® is an in vitro diagnostic test measuring the host immune response at the tumor site. It provides a robust, precise, and quantitative assessment of lymphocytic infiltration and has been shown to predict outcome and response to therapies in several indications. In March 2020, the World Health Organization (WHO), in its latest edition of the Digestive System Tumours, introduced immune response as an essential and desirable diagnostic criterion for colorectal cancer, in addition to traditional histological parameters. This was followed in July, by the entering of Immunoscore® in the 2020 European Society of Medical Oncology (ESMO) Clinical Practice Guidelines for Diagnosis, Treatment and Follow-up for Localised Colon Cancer. Immunoscore® is currently being investigated in a broad number of clinical studies and cancer indications for establishing its performance as a prognostic factor as well as a predictive factor for response to drugs, notably chemotherapies and immunotherapies.

Immunoscore® Colon is the first IVD diagnostic test of our Immunoscore® portfolio for which a comprehensive corpus of clinical data demonstrating its clinical utility associated with TNM scoring in the management of localized colon cancer has been published. Additional immune-based assays in the same portfolio are used as clinical trial assays to support translational research and clinical development. Those assays enable Multiplex Spatial Tissue Analysis and combine proprietary multiplexed immunohistochemistry, advanced image analysis and computerized algorithms.

Immunoscore® is commercially available in more than 20 countries.
About HalioDx

The Immune Response to Cancer Diagnostics

HalioDx is an immuno-oncology diagnostic company providing oncologists and drug development organizations with first-in-class Immune-based diagnostic products and services to guide cancer care and contribute to precision medicine in the era of immuno-oncology and combination therapies.

Leveraging the pioneering work of Dr Jérôme Galon, HalioDx provides a unique range of immune scoring solutions including its flagship Immunoscore® assay for the assessment of the immune contexture of a tumor, as a key determinant of patients’ outcomes and response to cancer treatments.

HalioDx has developed a unique Biopharma partnering ecosystem for the identification of clinically relevant biomarker signatures, the demonstration of their clinical utility in trials and the development and commercialization of resulting diagnostic or companion diagnostic tests. Our programs draw on our expertise and focus on immuno-oncology, a complete suite of genomic and proteomic biomarker profiling services, a world-class data analysis and biostatistics platform, and CLIA-certified laboratories with compliant facilities in Europe and in the US to develop, manufacture, register and market in vitro diagnostic (IVD) products. HalioDx has rapidly become the preferred partner of Biopharma developing therapeutic antibodies, vaccines, chemotherapies, oncolytic peptides, and CAR-T cell therapies.

For more information, please visit our websites www.haliodx.com and www.immunoscore-colon.com and follow the company on Twitter, Linkedin and Youtube.

Immunoscore® is a registered trademark of Inserm licenced to HalioDx. Brightplex®, TMExplore™ and Immunosign® are registered trademarks of HalioDx.

About FFCD

The Francophone Federation of Digestive Oncology

Association known as “Law of 1901”, an academic cooperative group, specialized in digestive cancerology, has been setting up, since June 12, 1981, in complete independence research and scientific communication projects or training in the fields of digestive cancer (physiopathology, diagnosis and therapy).

The Francophone Federation of Digestive Oncology brings together all the digestive oncology specialists (gastroenterologists, surgeons, oncologists, radiotherapists, radiologists, anatomopathologists) in more than 300 investigation centers on the French territory. It has developed exceptional scientific expertise in cancer treatment by initiating and coordinating clinical and biological trial at the national and international level.

For more information, visit www.ffcd.fr  and follow @ffcd_cancerdig on Twitter.

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