Yervoy, Local Injection of Candidate Therapy Tilsotolimod Shrink Advanced Melanoma Tumors, Trial Shows

Yervoy, Local Injection of Candidate Therapy Tilsotolimod Shrink Advanced Melanoma Tumors, Trial Shows
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Tilsotolimod

A combination of Yervoy (ipilimumab) and Idera Pharmaceuticals’ investigational tilsotolimod reduced tumors in four out of 10 advanced melanoma patients included in a Phase 1/2 trial.

Findings from the ILLUMINATE-204 trial (NCT02644967) were presented at the European Society for Medical Oncology (ESMO) 2018 Congress, Oct. 19-23 in Munich, Germany. The poster was titled “Intratumoral (IT) Injection of the TLR9 agonist tilsotolimod (IMO-2125) in combination with ipilimumab (ipi) triggers durable responses in PD-1 inhibitor refractory metastatic melanoma (rMM): Results from a multicenter, phase I/II study.”

Tilsotolimod (previously known as IMO-2125) is designed to promote a broad activation of the immune system. The investigational therapy activates the Toll-like receptor 9 (TLR9), a protein found in certain immune cells, resulting in greater recognition and killing of tumor cells by the immune system.

The treatment is being studied in combination with immune checkpoint inhibitors, including Bristol-Myers Squibb’s CTLA-4 inhibitor Yervoy or Merck’s PD-1 inhibitor Keytruda (pembrolizumab) — which remove the brakes from immune cells and improves their ability to fight cancer.

ILLUMINATE-204, which is recruiting participants in the U.S., was designed to investigate tilsotolimod, in combination with either Yervoy or Keytruda, in patients with advanced melanoma whose disease progressed after therapy with PD-1/PD-L1 inhibitors.

Patients receive tilsotolimod in nine tumor injections, while Keytruda and Yervoy are injected into the bloodstream.

Results from the first 21 patients treated with tilsotolimod and Yervoy showed that eight patients (39%) responded to the treatment, including six of the 17 who had never received Yervoy, and two of the four who had failed prior Yervoy treatment.

Seven of these patients also experienced reductions in distant, tilsotolimod-untreated tumors. An additional four patients who failed to achieve a response in the injected tumors also showed tumor shrinkage in uninjected lesions.

The findings suggest that tilsotolimod helps overcoming resistance to Yervoy and that the combination activates immune cells that travel throughout the body to eliminate distant tumors.

“The data presented at ESMO demonstrate that in patients with melanoma progressing on or after PD-1 inhibitor therapy, injecting a single tumor lesion with tilsotolimod, in combination with ipilimumab, produced tumor shrinkage in distant uninjected lesions in nearly all patients with reported responses,” Adi Diab, MD, assistant professor at The University of Texas MD Anderson Cancer Center and trial’s lead investigator, said in a press release.

Yervoy’s efficacy has been linked with a robust expression of a group of proteins called major histocompatibility complex (MHC)-I; these proteins are important for the presentation of tumor proteins (antigens) to immune cells.

However, even patients with low MHC-I expression showed signs of clinical response to the combination, supporting the hypothesis that tilsotolimod improves the efficacy of Yervoy in these patients.

“Clinical responses were seen in tumors where MHC class I expression was low at baseline,” Diab said. “Our findings suggest that combining tilsotolimod with ipilimumab may overcome this mechanism of resistance to anti-CTLA-4 monotherapy.”

“The clear demonstration of tumor shrinkage in uninjected tumors following the injection of a single tumor lesion with tilsotolimod provides clinical confirmation of our translational data and addresses an important frequently asked question,” said Joanna Horobin, Idera’s chief medical officer.

“Additionally, the new observation that tilsotolimod may overcome the requirement for MHC class 1 expression for effective anti-tumor therapy with ipilimumab in patients otherwise unlikely to respond is a very exciting finding and addresses another important question regarding the contribution of tilsotolimod when given in combination with ipilimumab,” she added.

The post Yervoy, Local Injection of Candidate Therapy Tilsotolimod Shrink Advanced Melanoma Tumors, Trial Shows appeared first on Immuno-Oncology News.

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