tilsotolimod (IMO-2125)

P1, N=25, Terminated, Gustave Roussy, Cancer Campus, Grand Paris | N=72 --> 25 | Active, not recruiting --> Terminated; The part A of the trial has been completed according to the protocol. The part B has not been opened because of unfeasibility (experimental products not yet available).

P2, N=53, Completed, Idera Pharmaceuticals, Inc. | Phase classification: P1/2 --> P2

P3, N=481, Terminated, Idera Pharmaceuticals, Inc. | Trial completion date: Sep 2021 --> Jun 2021 | Active, not recruiting --> Terminated; Lack of Efficacy

The primary objective of this study is to assess the safety of the combination of IRE with IMO-2125 (a toll-like receptor 9 ligand) and/or nivolumab in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). Consequently, there is an urgent need for innovative and radically different treatment approaches. Should electroimmunotherapy establish an effective and durable anti-tumor response, it may ultimately improve PDAC's dismal prognosis.

This review focuses on the current status of IT agents currently under clinical trials in melanoma. Reviewed therapies include T-VEC, T-VEC with immune checkpoint inhibitors including ipilimumab and pembrolizumab or other agents, RP1, OrienX010, Canerpaturev (C-REV, HF10), CAVATAK (coxsackievirus A21, CVA21) alone or in combination with checkpoint inhibitors, oncolytic polio/rhinovirus recombinant (PVSRIPO), MAGE-A3-expressing MG1 Maraba virus, VSV-IFNbetaTYRP1, suicide gene therapy, ONCOS-102, OBP-301 (Telomelysin), Stimulation of Interferon Genes Pathway (STING agonists) including DMXAA, MIW815 (ADU-S100) and MK-1454, PV-10, toll-like receptors (TLRs) agonists including TLR-9 agonists (SD-101, CMP-001, IMO-2125 or tilsotolimod, AST-008 or cavrotolimod, MGN1703 or lefitolimod), CV8102, NKTR-262 plus NKTR-214, LHC165, G100, intralesional interleukin-2, Daromun (L19IL2 plus L19TNF), Hiltonol (poly-ICLC), electroporation including calcium electroporation and plasmid interleukin-12 electroporation (pIL-12 EP), IT ipilimumab, INT230-6 (cisplatin and vinblastine with an amphiphilic penetration enhancer), TTI-621 (SIRPαFc), CD-40 agonistic antibodies (ABBV-927 and APX005M), antimicrobial peptide LL37 and other miscellaneous agents.

P1/2, N=53, Completed, Idera Pharmaceuticals, Inc. | Active, not recruiting --> Completed | Trial completion date: May 2020 --> Feb 2020 | Trial primary completion date: May 2020 --> Feb 2020

Funding: Idera Pharmaceuticals. Clinical trial identification: NCT02644967.

Funding: Idera Pharmaceuticals. Clinical trial identification: NCT03052205.

The checkpoint inhibitors pembrolizumab, nivolumab as monotherapy, and nivolumab in combination with ipilimumab are approved in the US for treatment of patients with previously treated microsatellite instability-high (MSI-high) or mismatch repair-deficient metastatic colorectal cancer (CRC)...ILLUMINATE-206 will comprise multiple cohorts, including patients with immunotherapy-naïve, MSS-CRC who have received at least 2 prior regimens of therapy for advanced or metastatic disease including fluoropyrimidine-, oxaliplatin-, and irinotecan-based regimens...Additional patients may be enrolled in Part 1 after review of the data from the initial safety run-in of 10 patients. Based on data from Part 1, the cohort may be expanded during Part 2.

Tilsotolimod was generally well tolerated and induced alterations in the tumor microenvironment, including immune checkpoint upregulation, activation of dendritic cells, and induction of Type-I IFN signaling. Additional clinical studies of tilsotolimod in combination with checkpoint inhibitors are underway (NCT03445533, NCT03865082, and NCT02644967).

P3, N=454, Active, not recruiting, Idera Pharmaceuticals, Inc. | Recruiting --> Active, not recruiting