IO-108 shows promising results in the treatment of advanced relapsed or refractory solid tumours

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Published: 20 Apr 2023
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Dr Matthew Taylor - Providence Cancer Institute, Portland, USA

Dr Matthew Taylor speaks to ecancer about a first-in-human phase 1 trial of IO-108, an antagonist antibody targeting LILRB2 (ILT4), as monotherapy and in combination with pembrolizumab in adult patients with advanced relapsed or refractory solid tumours. 

The study investigated escalating dose cohorts of IO-108 as monotherapy or in combination with pembrolizumab. 

Dr Taylor enlists the secondary and exploratory objectives of the study. 

He then explains the results and the future of this study. 

The study results suggested that further development of IO-108 is justified, both as monotherapy and in combination with anti-PD-(L)1 for patients with advanced solid tumours. 

This is a phase I, first in human, clinical trail evaluating the drug called IO-108 which is a fully human IgG4 antibody that targets the protein called LILRB2. This was a phase I clinical trial for patients with advanced treatment refractory solid tumours.

It was a phase I dose escalation clinical trial; it was also a combination cohort with pembrolizumab. Again, this was available to patients with advanced treatment refractory solid tumours. The primary endpoint was safety and tolerability with secondary endpoints looking at treatment efficacy.

The results basically showed that the study drug, IO-108, was very well tolerated, so had an excellent safety profile. There were no dose limiting toxicities; a maximum tolerated dose was not found, despite escalating all the way through the pre-planned dose of 1800mg every three weeks. So the proposed recommended phase II dose is 1200mg every three weeks. Other than the excellent safety and tolerability profile it was very exciting to see that the drug showed some very encouraging signs of clinical efficacy. We had one patient with Merkel cell carcinoma who had previously been treated with anti-PD-1 and anti-CTLA-4 therapies and had refractory advancing disease. That patient developed a complete response on treatment with IO-108 as monotherapy, so that was incredibly exciting to see. We also had two patients with advanced treatment refractory cholangiocarcinoma and another patient with colorectal cancer, all of whom had microsatellite stable disease and those three patients had partial responses. So very encouraging to see how this drug is showing such impressive clinical activity in patients previously treated with standard therapies.

How might these results impact future trials involving refractory solid tumours?

What we’re going to see is this drug, IO-108, will be tested in further clinical studies, both as monotherapy and in combination with other immune checkpoint inhibitors targeting anti-PD-1, PD-L1 and possibly other immune checkpoint molecules. So we’re excited to see how this is going to change the landscape of treatment for patients with advanced solid tumours, particularly those who have been treated with standard therapies.

What are the next steps for this study?

The trial has multiple expansion cohorts that are ongoing right now with the drug as monotherapy as well as in combination with other anti-PD-1 immune checkpoint molecules. For the future of the drug, it’s going to be very exciting to see combinations with other immune checkpoint molecules targeting other targets such as CTLA-4, LAG-3 and others. 

To summarise, I suppose it’s just very exciting to see that the drug was so well tolerated with an excellent safety profile and showing some very impressive early signs of clinical efficacy. So we’re very excited to see this become a new therapy that we can offer to our patients in clinic.