TEST:

Immunoscore® IC Assay

We performed a comprehensive evaluation of liver-metastatic (LM) disease among mCRC patients enrolled in the phase II randomized AtezoTRIBE trial, that showed a modest benefit from the addition of atezolizumab (atezo) to 1st line FOLFOXIRI/bevacizumab (bev) and identified Immunoscore IC as a predictor of ICI efficacy in the proficient mismatch repair (pMMR) population... In our cohort of pMMR mCRC patients, the immune microenvironment of tumors with LM spread does not differ from that of tumors with no liver involvement. The presence or not of LM disease does not affect the efficacy of adding atezo to first-line FOLFOXIRI/bev, differently than Immunoscore IC.

This real-time approach not only enhances our understanding of the TME but also supports more informed decisions regarding trial enrollment, ultimately aiming to improve patient care and pharmaceutical strategies. Overall, this innovative approach promises to significantly improve the design and outcomes of early-phase clinical trials.

These results show that IS-IC and CPS informs on the prognosis of relapsing HNSCC patients treated with anti-PD1 and could be used to select patients who will benefit from adjuvant immunotherapy after salvage surgery.

First-line FOLFOXIRI/bevacizumab plus atezolizumab improves OS in patients with mCRC. In the pMMR group, patients with Immunoscore IC-high and/or TMB-high tumors are identified as a subgroup of interest to further develop this treatment.

We performed a comprehensive evaluation of LM among mCRC patients enrolled in the phase II randomized AtezoTRIBE trial, that showed a modest benefit from the addition of atezolizumab (atezo) to 1-line FOLFOXIRI/bevacizumab (bev) and identified Immunoscore IC as a predictor of ICI efficacy in the proficient mismatch repair (pMMR) population. We investigated the association of LM disease with tumor immune-related biomarkers – including MMR, TMB, Immunoscore IC, Immunoscore, Tumor-Infiltrating lymphocytes (TILs) assessed by optical microscope, PD-L1 expression by Tumor Proportion Score (TPS), and the immune 27-gene signature DetermaIO – and treatment outcome, in the cohort of patients with pMMR tumor enrolled in the AtezoTRIBE study. 151 (75%) out of 202 enrolled patients with pMMR tumor had LM... In our cohort of pMMR mCRC patients, the immune microenvironment of tumors with LM spread does not differ from that of tumors with no liver involvement. The presence or not of LM does not affect the efficacy of adding atezo to first-line FOLFOXIRI/bev, differently than Immunoscore IC.

These results suggest that baseline proportions of protumor M2 macrophages may predict disease relapse after axi-cel treatment. Following infusion, relapse is also associated with spatial enrichment of M-MDSC, whereas durable response is related to increases in T cell subpopulation densities inclusive of cytotoxic T cells, T helper, TC1/TC2 ratios and innate T-subpopulations. These findings suggest that axi-cel treatment drastically impacts tumor immune mobilization, infiltration and contexture, which correlates with long term response.

"Veracyte, Inc...today announced that two poster presentations taking place at SITC 2023, the annual meeting of the Society for Immunotherapy of Cancer, in San Diego from November 3-5 will demonstrate the potential for using the company’s novel tools to help advance the development of immuno-oncology drugs. These tools allow for better characterization of the tumor microenvironment (TME), which can enable new insights into drug response and mechanisms of resistance....'These conference presentations will show that Veracyte’s Brightplex and Immunoscore IC tools can offer scientists a clearer view of the tumor microenvironment, as well as data that could inform immuno-oncology drug development.'"

Experts will provide an in-depth review of the assay’s analytical performance, clinical relevance, and efficacy, with a focus on metastatic colorectal cancer (mCRC) and non-small cell lung cancer (NSCLC). Join us to engage in a dynamic discussion with our experts, addressing key questions, potential challenges, and future directions in harnessing Immunoscore® IC for precision immunotherapy.

"In colorectal cancer (CRC), the addition of atezolizumab to first-line FOLFOXIRI plus bevacizumab improved progression-free survival (PFS) in patients with previously untreated metastatic CRC...Thus, Immunoscore-IC could be a universal biomarker to predict response to PD-1/PD-L1 checkpoint inhibitor immunotherapy across multiple cancer indications. Therefore, cancer patient stratification (by Immunoscore-IC), based on the presence of T lymphocytes and PD-L1 potentially provides support for clinicians to guide them through combination cancer treatment decisions."

Background Adding atezolizumab (atezo) to FOLFOXIRI/bev prolongs PFS of mCRC patients (pts) in AtezoTRIBE trial...Conclusions IPs and IS by Lunit SCOPE IO provide a characterization of tumor microenvironment, being associated with Immunoscore, Immunoscore IC and TILs. Further development of AI-powered TILs analyses taking into account their densities may help identifying biomarkers of immunogenicity in mCRC.

Immunoscore-IC is a powerful tool to predict the efficacy of immune-checkpoint inhibitors (ICIs) in patients with NSCLC.

P2 | "Pts with IS IC-high and/or TMB high pMMR mCRC seem to derive a survival benefit from adding atezo to FOLFOXIRI/bev as upfront treatment. These findings deserve confirmation in a properly designed phase III trial."

P2 | "Pts with IS IC-high and/or TMB high pMMR mCRC seem to derive a survival benefit from adding atezo to FOLFOXIRI/bev as upfront treatment. These findings deserve confirmation in a properly designed phase III trial. Clinical trial information: NCT03721653."

The digital evaluation of tumor immune cell infiltrate by means of Immunoscore-IC or Immunoscore identifies the subset of patients with pMMR mCRC achieving more benefit from the addition of the anti-PD-L1 to the upfront treatment. Immunoscore-IC stands as the most promising predictor of benefit from ICIs.

P2 | "In first line metastatic MSS CRC, PolyPEPI1018 in combination with fluoropyrimidine/bevacizumab vaccine was safe and demonstrated early evidence of clinical activity. The study is open with 10 patients enrolled at time of submission. Clinical trial information: NCT05243862."

P2 | N=201 | AtezoTRIBE (NCT03721653) | "Veracyte...announced today that new data published online in The Lancet Oncology suggest that the company’s Immunoscore Immune Checkpoint (IC) assay may identify patients with metastatic colorectal cancer (mCRC) who are likely to benefit from the addition of immune checkpoint inhibitor (ICI) therapy to standard first-line treatment. The findings are from the randomized, controlled, phase II AtezoTRIBE trial, a multicenter Italian clinical study, sponsored by GONO Foundation. The vast majority of mCRC tumors (approximately 95 percent) have a proficient DNA mismatch repair (pMMR) system and are microsatellite stable. These tumors have low immunogenicity and do not derive benefit from immune checkpoint inhibitors."

"Veracyte, Inc. (Nasdaq: VCYT) announced today new data from a clinical research study demonstrating the ability of its Immunoscore Immune Checkpoint (IC) assay to predict which patients with metastatic non-small cell lung cancer (NSCLC) may benefit from immune checkpoint inhibitors (ICIs). The findings will be shared in an oral presentation at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago on June 6 at 1:15 p.m. CDT....Within the two cohorts, all patients (100 percent) with a 'high-risk' Immunoscore IC result relapsed in less than 18 months. In contrast, 34 percent and 33 percent of patients with a 'low-risk' Immunoscore IC result did not relapse for a period of at least 36 months, in each cohort....'Further, we believe the test’s use could help enable patients who are unlikely to respond to ICIs to enter into novel, combination-immunotherapy trials'."

These data underline that Immunoscore IC is a potent tool to predict the efficacy of ICIs in patients with NSCLC. Immunoscore IC characterized patients who are resistant to ICIs.