Esmo 2018 – Merck & Co fails to Sting

Oncology projects that disrupt the tumour microenvironment are hot property, and – after Aduro’s $225m deal with Novartis and Bristol-Myers Squibb’s $300m takeover of IFM Therapeutics – the Sting pathway is seen as particularly attractive. This is why the first clinical data with Merck & Co’s Sting agonist MK-1454, presented at Esmo, were so eagerly awaited. In the event, however, investors were left disappointed when the study yielded no remissions in its MK-1454 monotherapy cohort; and none of the six of 24 patients responding to MK-1454 plus Keytruda had earlier failed checkpoint blockade. Neither was there much from a trial of MK-4621, a Rig1 activator Merck got through its $115m takeout of Rigontec: the compound showed promising pharmacokinetics, but it was too early to comment on efficacy. The prize went unexpectedly to Roche’s RG7461, which generated four responses in 43 melanoma patients – all of whom had failed checkpoint blockade. The studies’ discussant, Dr Maria Grazia Daidone of Fondazione IRCCS Istituto Nazionale dei Tumori, said RG7461 was “the first tumour-targeted IL-2 variant with acceptable safety to display monotherapy activity”. Since Bristol paid $1.85bn for Nektar’s NKTR-214 there is no doubt about the importance of IL-2.

Selected tumour microenvironment disruptors
Project Mechanism Company Detail Trial ID
MK-1454 Sting agonist Merck & Co 0% ORR in monotherapy, 25% in Keytruda combo NCT03010176
MK-4621 Rig1 activator Merck & Co No dose-limiting toxicities NCT03065023
RG7461 FAP-targeted IL-2 variant Roche 9% ORR as monotherapy in checkpoint-progressed melanoma NCT02627274
AZD6738  ATR inhibitor Astrazeneca 24% ORR in imfinzi combo NCT02264678
Source: Esmo 2018.

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