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|
|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.|