SPICE: Analysis of enadenotucirev plus nivolumab in metastatic colorectal cancer patients during the dose escalation phase

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Published: 4 Oct 2019
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Prof Marwan Fakih - City of Hope National Medical Center, Duarte, USA

Prof Marwan Fakih speaks to ecancer at ESMO 2019 in Barcelona about the results from the phase I SPICE study, which investigated the combination of enadenotucirev plus nivolumab in metastatic tumours of epithelial origin.

He presents the latest results obtained from this study, in which the patients with metastatic colorectal cancer lived longer than expected and experienced a median overall survival of more than 12 months.

Prof Fakih believes there is more to be learned as prior studies have suggested enadenotucirev increases T-cell infiltration and may be synergistic to the action of some checkpoint inhibitors. However, biomarkers for this response are yet to be determined, along with the underlying mechanisms of synergy and resistance.

ecancer's filming has been kindly supported by Amgen through the ecancer Global Foundation. ecancer is editorially independent and there is no influence over content.

At this meeting we presented data on enadenotucirev in combination with nivolumab on a phase I clinical trial. The poster at this meeting was really focused on patients with colorectal cancer. This study included multiple histologies. What has been interesting is that in a large cohort of colorectal cancer enrolled on this study we have seen a significant number of disease stability but what we were impressed with is actually the fact that these patients on this study have lived longer than expected. The median overall survival of those patients was more than 12 months, despite the fact that these patients are refractory to all standards of care. So that’s considerably better than what you would expect with best supportive care or even with some of the approved agents in this area, such as regorafenib or trifluridine. Of note we have seen one patient with microsatellite stability who had low tumour mutation burden who had a very dramatic response to the combination of enadenotucirev and nivolumab. This patient had a BRAF mutation. So we are hopeful that it is possible that the attenuated adenovirus enadenotucirev is able to synergise somewhat in some patients in combination with checkpoint inhibitors.

Is this a novel treatment in this disease type?

Yes. I think there’s more to be learned. The prior studies have suggested that enadenotucirev increases T-cell infiltration in the tumour and results in an inflamed phenotype. It’s possible that that may result in basically some synergy with checkpoint inhibitors given the T-cell infiltration and the potential up-regulation of PD-1 in that setting. I think we need to figure out what are the biomarkers of response. We need to understand better the mechanisms of synergy and resistance as well.