A novel bifunctional fusion protein for combatting lung cancer

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Published: 21 Oct 2018
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Dr Luis Paz-Ares - Hospital Universitario, Madrid, Spain

Dr Luis Paz-Ares speaks to ecancer at ESMO 2018 in Munich about a clinical trial that uses a novel bifunctional fusion protein (M7824).

The findings include a high rate of response in patients whose tumours expressed high levels of PDL1, and links that to improved PFS in some patients.

Dr Paz-Ares concludes by describing exploratory avenues to expand research with the molecule.

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.

This is a bifunctional protein which is a fusion protein where it binds by one hand to the PD-L1 ligand and on the other hand is trapping TGF-β.

When it comes to employing this in clinical practice what are we reporting at this year’s conference?

This clinical trial here is a randomised study of two doses – 500mg versus 1200mg – of this very compound. The main result is that clinical efficacy is quite encouraging, particularly at a high dose with the response rate being in the range of 37% for patients which are PD-L1 positive, being particularly surprising for those patients with expression of PD-L1 in more than 80% of the cells, the response rate being 81%. PFS data are also consistent – 9.5 for the PD-L1 positive population, being more than 15 months for those which are PD-L1 high high. Safety data are purely favourable, just some pruritus, a skin rash and some keratoacanthomas or skin neoplasms.

When it comes to expanding the platform to include possibly other disease types and disease areas?

Yes, I would say this trial is somehow done. The next step will be in stage 4 patients, those previously untreated, because this trial was in pre-treated patients but we’ll go to untreated patients with high PD-L1 expression and do a randomised study comparing this new agent, M7824, as compared to pembrolizumab. The other area of main interest in lung cancer would be stage 3; because of the TGF-β inhibition factor apart from the PD-L1 inhibition, it makes a lot of sense to do trials in conjunction with radiation, so a trial of chemoradiation plus this agent is being planned at the present time.

And in combination with any other targeted agents?

As far as I know in lung cancer it’s not being planned.