PolyPEPI1018 is the first cancer vaccine to demonstrate promising results when combined with a PD-(L)1 inhibitor in late-stage microsatellite stable colorectal cancer (MSS CRC), a form of cancer —representing 96% of all metastatic CRC — historically resistant to checkpoint inhibitor immunotherapy. LONDON and BOSTON, June 03, 2024 (GLOBE NEWSWIRE) -- Treos Bio Limited, a clinical-stage biotechnology company using data science and proprietary biomarkers to develop precision peptide immunotherapies, today announced the presentation of results from its phase 2 OBERTO-301 study of the company’s lead product candidate, PolyPEPI1018, in combination with atezolizumab in patients with late-stage microsatellite stable metastatic colorectal cancer (MSS mCRC) at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. PolyPEPI1018 is an off-the-shelf, multi-peptide vaccine that has previously demonstrated the ability to induce immunological responses at both the peripheral and tumor levels, effectively turning immunologically ‘cold’ tumors into ‘hot’ ones. This was observed in first-line maintenance MSS mCRC (OBERTO-101) and late-stage MSS mCRC (OBERTO-201), providing a strong rationale for testing PolyPEPI1018 in combination with PD-(L)1 inhibitors in MSS mCRC. OBERTO-301 is a multicenter, open-label, phase 2 clinical trial, conducted at the Mayo Clinic in Minnesota, Florida and Arizona, evaluating the combination treatment of PolyPEPI1018 and atezolizumab in patients with MSS mCRC who have progressed on two or three prior treatment regimens. The primary endpoint of the study is the incidence and severity of treatment-related adverse events. Secondary endpoints include objective response rate, duration of response, progression-free survival, and overall survival. Key Study Findings: Patient Enrolment and Treatment: The study enrolled 18 patients with refractory non-MSI-H metastatic colorectal cancer who were administered PolyPEPI1018 (1.2 mg) and atezolizumab (1,200 mg) every three weeks. Of these, 67% had undergone three or more prior therapy lines, and 44% had active liver metastasis.Safety and Tolerability: PolyPEPI1018 in combination with atezolizumab was well tolerated, with no unexpected toxicities or serious adverse events related to treatment.Survival Benefits: The median overall survival (mOS) was 12.8 months (95% CI 8.8 - NE) and the 12-months survival was 60%; this compares favorably to the historical data of 7.1 months and 27% respectively for atezolizumab monotherapy in a similar patient population. Differences between the survival of patients with and without liver metastasis were not statistically significant (HR: 0.58 [95% CI 0.18 - 1.90]; P=0.36): Patients without active liver metastases (NLM) had a 12-month overall survival (OS) estimate of 67% and a median OS of 16.5 months.Patients with active liver metastases (LM) had a 12-month OS estimate of 50% and a median OS of 8.6 months. Progression-Free Survival (PFS) and Disease Control Rate (DCR): The median PFS was 2.7 months (95% CI 1.4-4.0), and the DCR was 61%. No tumor responses by RECIST 1.1 were observed.Immune Response and Tumor Microenvironment: PolyPEPI1018-specific CD8+ and/or CD4+ T cell responses were detected in 13 out of 16 subjects (ex vivo FluoroSpot), complemented by humoral responses against multiple PolyPEPI1018-antigens. Patients with available biopsy pairs (n=8) showed significant increases in average PD-L1 expression (IC%, p=0.029) and CD8+ tumor infiltrating lymphocytes (TILs, p=0.019) post-treatment, demonstrating an immune conversion from ‘cold’ to ‘hot’ tumor.Correlation with PFS and Immunological Markers: Patients with increased PFS (>12 weeks) showed significant increases in both post-treatment PD-L1 expression (p=0.007) and TILs (p=0.016) versus patients with PFS ≤ 12 weeks. Pre-treatment levels were not prognostic.T Cell Responses and Survival: Patients with robust CD8+ T cell responses had improved OS compared to patients with poor immunological responses (HR=0.13, p=0.022). Dr. Joleen Hubbard, Deputy Director for Clinical Research at Allina Health Cancer Institute and principal investigator of three clinical studies with PolyPEPI1018 at Mayo Clinic, commented, “MSS mCRC patients represent the largest population of mCRC, most of whom have poor-prognostic metastatic sites, where survival beyond one year with standard care is rare. In this latest study, I was particularly intrigued by the correlative data showing that the combination of PolyPEPI1018 and atezolizumab actually increased TILs and PD-L1 expression, which correlated with improved PFS. I am enthusiastic about the potential of PolyPEPI1018 in the development of new treatment alternatives for this challenging disease.” “We are highly encouraged by the consistency observed across three clinical trials in MSS mCRC in different settings. The survival and biomarker data from this study further highlight the potential benefit of PolyPEPI1018 either as an add-on to standard-of-care or as part of a chemo-free IO-IO combination for treating refractory MSS mCRC. We look forward to progressing PolyPEPI1018 to randomized, controlled trials in combination with chemotherapy, biologics, and PD-(L)1 inhibitor,” added Christopher C. Gallen, M.D., Ph.D., CEO of Treos Bio. The poster can be accessed at http://treosbio.com/index.php/publications-2/ References: Hubbard et al, Safety and Activity of PolyPEPI1018 Combined with Maintenance Therapy in Metastatic Colorectal Cancer: An Open-Label, Multicenter, Phase Ib Study. Clin Cancer Res 2022.Hubbard et al, PolyPEPI1018 Vaccine in Combination with TAS-102 in Participants with Late-Stage Microsatellite-Stable Metastatic Colorectal Cancer (MSS mCRC): A Phase Ib Study to Evaluate Safety, Tolerability, Immunogenicity, and Efficacy (OBERTO-201). ASCO2023.Eng et al, Atezolizumab with or without Cobimetinib versus Regorafenib in Previously Treated Metastatic Colorectal Cancer (IMblaze370): A Multicentre, Open-Label, Phase 3, Randomised, Controlled Trial. Lancet Oncol 2019. About Colorectal Cancer:Colorectal cancer (CRC) is the third most common cancer and cause of cancer-related deaths in the United States and worldwide. There are approximately 1.4 million people living with colorectal cancer in the United States. Current treatments for CRC include surgery and chemotherapy in early stages, and chemotherapy, biologics, and targeted therapies in later stages. Microsatellite stable (MSS) CRC accounts for approximately 85% of all colorectal cancers and approximately 96% of all metastatic CRC. Patients with MSS CRC do not benefit from available immunotherapies. About PolyPEPI1018:PolyPEPI1018, Treos’ lead product candidate, is an immunotherapy in clinical development for the treatment of metastatic colorectal cancer, with plans to incorporate a candidate companion diagnostic in future clinical trials. The therapy is in development as an add-on to first-line maintenance therapy and to third-line treatment. PolyPEPI1018 has been developed using Treos’ proprietary PASCal computational tool to identify Personal EPItopes (PEPIs) likely to induce multiple tumor-specific T cell responses in a patient. Prior to the OBERTO-301 clinical trial, PolyPEPI1018 was evaluated in two Phase Ib clinical trials: OBERTO-101 in the first-line maintenance setting and OBERTO-201 in the advanced, refractory setting of MSS mCRC. These trials explored treatment combinations that had not been previously tested. In the first-line maintenance setting, adding PolyPEPI1018 to fluoropyrimidine and bevacizumab led to unprecedented tumor responses according to RECIST v1.1 and dose-dependent improvements in progression-free survival (PFS). To explore the potential of PolyPEPI1018 in treating advanced, refractory MSS mCRC, Treos adopted a stepwise approach. This involved initially assessing the safety, immunogenicity, and preliminary efficacy of PolyPEPI1018 as an add-on to standard chemotherapy, TAS-102 (OBERTO-201). Following this, the effect of PolyPEPI1018 in combination with an experimental immunotherapy in MSS CRC, atezolizumab, was tested in a similar patient population (OBERTO-301). Treos now plans to advance the testing of PolyPEPI1018 in a randomized, controlled phase 2 study comparing a complex chemo-immunotherapeutic regimen to standard of care. About Treos Bio Limited:Treos Bio develops precision peptide cancer immunotherapies combined with novel biomarkers using proprietary computational data science integrating HLA genetics, tumor profile, and clinical outcome of thousands of real subjects. Treos has conducted three clinical trials in the United States and the European Union of its lead candidate, PolyPEPI1018, an off-the-shelf immunotherapy for the treatment of metastatic colorectal cancer. Treos has completed preclinical development of additional off-the-shelf immunotherapies for ovarian, breast, bladder, gastric, lung cancers, and melanoma. The Company is also developing off-the-shelf immunotherapies personalized to an individual patient’s HLA genotype for several types of solid tumors. Treos has raised $45 million to date. More information can be found at www.treosbio.com. Media Contact: Daniel LevineLevine Media Group+1 (510) 280-5405danny@levinemediagroup.com
