INFINITIVE: ImmuNotherapy For PatIeNts wIth colorecTal LIVer MEtastases
Nelitolimod is a classC toll-like receptor 9 (TLR9) agonist that binds to TLR9 receptors on myeloid-derived suppressor cells(MDSCs) and helps reshape the tumor microenvironment (TME) and promote antitumor immunity. Investigators hypothesize that Nelitolimod can induce antitumor immune response in CRLM when administered regionally to the liver via a TriNav Pressure Enabled Drug Delivery (PEDD) catheter without compromising surgical feasibility or patient safety. The study objective is to investigate the feasibility and safety of an innovative immunotherapeutic approach for patients with CRLM designed to overcome the immunosuppressive TME in CRLM. Investigators hypothesize that this investigational neoadjuvant treatment will be well tolerated and will not prevent patients from undergoing successful, safe CRLM liver resections. Investigators will assess the safety and feasibility of Nelitolimod given via TriNav PEDD in 10 patients with CRLM prior to liver resection. Patients will receive standard treatment with chemotherapy and then undergo placement of the PEDD catheter. Patients will then receive 3 doses of Nelitolimod before undergoing liver resection.
• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. A signed informed consent must be obtained prior to conducting any study-specific procedures.
• Male or female adults 18 years of age or older on day of signing informed consent.
• Radiographically confirmed metastatic adenocarcinoma to the liver from a colon or rectum primary tumor that is amenable to resection. TXNXM1+
• Only participants with liver-limited, resectable metastatic disease are eligible for participation (ablations are allowed to achieve an R0 intention-to-treat outcome).
• Only participants with pMMR (mismatch repair-proficient)/MSS mCRC are eligible. Microsatellite status should be performed according to the local standard of practice. (e.g., immunohistochemistry \[IHC\] and/or polymerase chain reaction \[PCR\], next-generation sequencing). Subjects with unknown or indeterminant results for either test at the time of enrollment are not eligible at investigators discretion.
• Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 1.
• Patients with synchronous disease who are planned to undergo liver and resection of primary are allowed.
• Total neoadjuvant therapy (TNT) for rectal cancers allowed.
• In the event the patient has had prior oxaliplatin-based adjuvant chemotherapy after resection of primary tumor, a minimum interval of 6 months should have passed prior to enrollment into the study.
• Patients must have completed standard of care FOLFOX/ FOLFIRI/FOLFIRINOX as part of pre- operative systemic therapy.
• Meets resectability criteria (all criteria MUST be met):
‣ Tumors that can be resected completely (R0), while leaving an adequate future liver remnant (defined under c.)
⁃ The ability to preserve two contiguous hepatic segments with preservation of adequate vascular inflow and outflow as well as biliary drainage
⁃ The ability to preserve adequate future liver remnant (\>20 percent in a healthy liver; \>30 percent after chemotherapy)
• Hematologic parameters defined as:
‣ Absolute neutrophil count (ANC) ≥ 1000 cells/mm3
⁃ Platelet count ≥ 100,000/mm3
⁃ Hemoglobin ≥ 8 g/dL
• Blood chemistry levels defined as:
‣ AST, ALT, alkaline phosphatase ≤5 times upper limit of normal (ULN)
⁃ Total bilirubin ≤2x the ULN. Patients with Gilbert Syndrome should have a serum bilirubin ≤ 4x ULN and a direct bilirubin ≤2x ULN to be eligible.
• Adequate renal function as estimated by glomerular filtration rate (eGFR) \>30 L/min determined based on the Cockcroft-Gault formula.
• Anticipated life expectancy greater than 6 months.
• Women of childbearing potential (WOCB) receiving systemic therapy should use effective contraception during treatment and for at least 9 months after the last investigational agent. Patients with partners who could become pregnant should use effective contraception during treatment and for 6 months after the last dose of investigational agent.