Results from the phase I ICONIC trial

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Published: 4 Jun 2018
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Dr Timothy Yap - MD Anderson Cancer Center, Houston, USA

Dr Yap speaks with ecancer at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting about data from the ICONIC trial of ICOS agonist antibody JTX-2011, a first-in-class drug.

He outlines the mechanistic and pharmacodynamic rationale behind developing an ICOS agonist, and dosages in the ICONIC trial of JTX-2011 with or without nivolumab in advanced cancers.

Dr Yap highlights responses in gastric, breast and lung cancers, and introduces ongoing trials for JTX-2011 in combination with CTLA-4 checkpoint therapy.

I presented the phase I and II clinical trial of the first in class ICOS agonist from Jounce Therapeutics called JTX-2011 given as monotherapy and also in combination with the PD-1 inhibitor called nivolumab.

This trial was done in patients with advanced solid tumours.

The importance of ICOS as a therapeutic target, ICOS stands for inducible co-stimulator of T-cells, the importance of ICOS as a therapeutic target really stems from early clinical trials where the emergence of ICOS high CD4 T-cells was observed in patients receiving ipilimumab, which is the CTLA-4 inhibitor.

Importantly, these findings correlated with better clinical outcomes, including survival.

These clinical data, as well as other preclinical data, provided a strong rationale for the development of ICOS as a therapeutic target.

So in this phase I and II clinical trial we assessed the safety and tolerability of this ICOS agonist called JTX-2011 as monotherapy and in combination with nivolumab and also established the maximum tolerated dose and the recommended phase II dose of this drug as monotherapy and also in combination.

Secondary objectives included pharmacokinetic studies as well as pharmacodynamics studies with this trial.

We also undertook multiple exploratory objectives as well in peripheral blood samples taken at multiple time points and also in paired tumour biopsies from patients who received either the monotherapy or the combination of JTX-2011 plus nivolumab.

Overall, this drug, JTX-2011, was found to be safe and well tolerated, both as monotherapy and also in combination with nivolumab.

We also observed preliminary anti-tumour activity with objective responses in gastric cancer and also in triple negative breast cancer patients who were IO naïve.

We also observed a disease control rate of nearly 60% in patients with non-small cell lung cancer, very advanced non-small cell lung cancer, who were all PD-1 failures.

So, one of the exciting things on this study was the observation of the emergence of ICOS high CD4 T-cell populations in patients who were actually responding.

So, seven out of seven patients who actually potentially were getting clinical benefit from this drug either as monotherapy or in combination with nivolumab actually had this emergence of ICOS high CD4 T-cells.

But patients who actually progressed, ten out of ten did not have the emergence of this ICOS high CD4 T-cell population.

Currently this ongoing clinical trial is now assessing a new combination with JTX-2011 given together with the CTLA-4 inhibitor ipilimumab.

We believe that we have identified a potential pharmacodynamic biomarker of response to JTX-2011 with this emergence of ICOS high CD4 T-cell population in these patients who are on either the monotherapy or the combination with nivolumab.

That sounds like a lot. When can we expect a little bit more from either of the expansion trials? Is there any timeline we can look towards?

We’re currently analysing a lot of the translational correlative studies that were done in patient samples that were taken from this ongoing study.

We hope to present some of that at a later meeting, either later this year or sometime early next year.