SITC18: Aduro finds some activity with STING agonist

Partial responses and stabilized disease were seen in some patients. (Krzysztof Niewolny/Unsplash)

Aduro Biotech has reported its first data for STING agonist ADU-S100, hoping to rebuild confidence in the mechanism after lackluster data from Merck last month.

At first glance, it seems to have succeeded, with signs of efficacy for ADU-S100 given on its own—something that Merck’s study was unable to demonstrate with its STING (stimulator of interferon genes) agonist MK-1454 at the European Society for Medical Oncology meeting last month.

The phase 1 results reported at the Society for Immunotherapy of Cancer annual meeting in Washington, D.C., come from an open-label study in 41 heavily pretreated patients with advanced solid tumors or lymphomas who were given the drug by direct injection into tumor sites at escalating doses.

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It’s primarily a safety study, but Aduro says two of 40 evaluable patients (5%) had a partial response to the drug—one with Merkel cell carcinoma and another with parotid gland cancer who had received prior anti-PD-1 therapy—while another 11 patients saw their disease stabilize.

The company also reports no dose-limiting toxicities with ADU-S100, as well as encouraging biomarker data including elevations in systemic cytokines and infiltration of cancer-killing CD8+ T cells in some tumors.

Given that it enrolled a very sick patient population, there was a very high discontinuation rate in the study, mainly because so many patients saw disease progression, opted to come off therapy or died. However, three patients with stable disease remain on treatment, including one with collecting duct carcinoma who has been in the study for more than a year, according to Aduro.  

Merck revealed at ESMO that MK-1454 has zero activity as a monotherapy but did manage to achieve a partial response rate of 24% when combined with PD-1 inhibitor Keytruda (pembrolizumab)—although crucially none of those were seen in patients who had previously failed checkpoint inhibitor therapy.

The read-out raised questions about whether STING-targeted drugs used in humans will mirror the startling results seen in animal studies, and despite the glimmers of efficacy seen in the SITC study the jury is still out. The drugs are designed to kick-start an innate immune response against cancer cells in the tumor microenvironment.

Aduro CEO Stephen Isaacs said the biotech is “encouraged by the data” and is expanding the trial to include additional patients with “select tumor types”, as well as adding a combination arm with Bristol-Myers Squibb’s CTLA4 inhibitor Yervoy (ipilimumab) that will look specifically at melanoma patients who have relapsed or are refractory to PD-1 inhibitors.

Meanwhile, Aduro is running a second phase 1b study of ADU-S100 alongside its PD-1 inhibitor spartalizumab, which has 50 subjects enrolled so far and according to the company has shown preliminary evidence of clinical responses.

“The observation of clinical benefit in patients who received prior PD-1 therapy may provide further evidence supporting the synergy between STING and checkpoint inhibitor therapy that was previously demonstrated by our preclinical results,” said Isaacs.

The new data are also encouraging for Novartis, which paid $200 million upfront for rights to Aduro’s STING program back in 2015 .