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Injection of IP-001 into thermally ablated solid tumors

ABSTRACT: Background and study aims Treatment in patients with advanced colorectal cancer, (CRC) non-small cell lung cancer (NSCLC) and soft tissue sarcoma (STS) represent a significant unmet need. Local thermal ablation of tumor tissue using techniques such as radiofrequency ablation (RFA) or stereotactic radiotherapy is an established treatment option for different tumors, in particular, CRC and NSCLC. There is strong nonclinical and early clinical evidence that combining thermal ablation with the investigational product, 1.0% IP-001 for Injection might be able to turn ‘cold’ tumors into ‘hot’ tumors, inducing a long-term systemic immune response mediated by the patient’s immunological defense system against any remaining tumor cells both at the site of the ablation treatment and those that are outside or distant from the treated area (known as the abscopal effect). The 2 components of treatment play unique roles in inducing an antitumor immune response: 1. During thermal ablation, treated tumor undergoes immunogenic cell death via a well-defined heat gradient 2. Adding 1.0% IP-001 for Injection elicits a tumor-specific adaptive immune response As a result, it is hypothesized that ablation + IP-001 can be deployed against a wide variety of tumor types to induce customized immune activation against a patient’s own, unique cancer. Who can participate? Adult patients with confirmed CRC, NSCLC, or STS What does the study involve? In this study, a solid tumor will first be thermally ablated by a standard ablation modality, and then 1.0% IP-001 for Injection will be injected into the area of the ablated tumor. Patients can be treated every 6 weeks for up to 4 treatments with RFA + 1.0% IP-001 for Injection.

DISEASE(S): Non-small Cell Lung Cancer And Soft Tissue Sarcoma,Colorectal Cancer

PROVIDER: 2761466 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Project description:BACKGROUND: Preclinical studies have demonstrated that pharmacological mobilization and recruitment of endogenous bone marrow stem cells and immunoregulatory cells by a combination of plerixafor and low-dose tacrolimus (MRG-001) improves wound healing, promotes tissue regeneration and prevents allograft rejection. This first‐in‐human phase I dose‐escalation study evaluates the safety, tolerability, pharmacokinetics and pharmacodynamics of MRG-001, a novel fixed-dose combination drug. METHODS: In this Phase 1, double‐blind, randomized, placebo-controlled study, multiple ascending dose (MAD) cohorts are randomized to receive MRG-001 containing up to 0.02 mL/kg (plerixafor 24 mg/mL and tacrolimus 0.5 mg/mL) or saline placebo, subcutaneously every other day (SC, QAD) for 5 days (ClinicalTrials.gov: NCT04646603)The primary outcome is safety and tolerability. Safety and functional assessments are performed throughout the study. Blood samples are collected to evaluate systemic exposure. Fluorescence-activated cell sorting analysis and RNA expression of peripheral blood mononuclear cells (PBMCs) are used to evaluate the pharmacodynamics. RESULTS: Fourteen subjects received MRG-001 and 7 received a placebo. MRG-001 is safe and well-tolerated over the selected dose range. No deaths or severe adverse events are reported. There are no clinically significant laboratory changes after MRG-001 administration, apart from the predicted generalized leukocytosis. The intermediate dose group (0.01 mL/kg) showed the most significant white blood cell mobilization over time and increased by 2-4 fold from baseline and returned to baseline levels prior to the next injection. Circulating immune cells including FOXP3+ regulatory T cells and hematopoietic stem cells (CD45IntCD34+) increased significantly after MRG-001 injection. PBMC RNA sequencing and gene set enrichment analysis revealeds 31 down-regulated pathways in the intermediate dose MRG-001 group compared to no changes in the placebo group. CONCLUSION: MRG-001 is safe and well-tolerated across the full dose ranges tested. MRG-001 may be a clinically useful therapy for immunoregulation and tissue regeneration. A Phase II trial to treat severely and critically ill COVID-19 patients with MRG-001 has been initiated (NCT04646603) and a second phase II trial will explore the potential of MRG-001 to accelerate wound healing (NCT05844527),

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Injection of IP-001 into thermally ablated solid tumors

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