Phase Ib study of MIW815 (ADU-S100) in combination with spartalizumab (PDR001) in patients (pts) with advanced/metastatic solid tumors or lymphomas.

person Funda Meric-Bernstam Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, TX info_outline Funda Meric-Bernstam, Shahneen Kaur Sandhu, Omid Hamid, Anna Spreafico, Stefan Kasper, Reinhard Dummer, Toshio Shimizu, Neeltje Steeghs, Nancy Lewis, Craig C. Talluto, Sinead Dolan, Andrew Bean, Robert Brown, Damian Trujillo, Nitya Nair, Jason J. Luke

Authors person Funda Meric-Bernstam Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, TX info_outline Funda Meric-Bernstam, Shahneen Kaur Sandhu, Omid Hamid, Anna Spreafico, Stefan Kasper, Reinhard Dummer, Toshio Shimizu, Neeltje Steeghs, Nancy Lewis, Craig C. Talluto, Sinead Dolan, Andrew Bean, Robert Brown, Damian Trujillo, Nitya Nair, Jason J. Luke Organizations Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, TX, Peter MacCallum Cancer Centre, The University of Melbourne, Melbourne, Australia, The Angeles Clinic and Research Institute, Los Angeles, CA, Princess Margaret Hospital, Toronto, ON, Canada, Department of Medical Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany, University of Zürich, Zürich, Switzerland, National Cancer Center Hospital (NCCH), Tokyo, Japan, Netherlands Cancer Institute, Amsterdam, Netherlands, Novartis Pharmaceuticals Corporation, East Hanover, NJ, Novartis Institutes for BioMedical Research, Cambridge, MA, Aduro Biotech Inc., Berkeley, CA, Aduro Biotech, Berkeley, CA, The University of Chicago Medicine, Chicago, IL Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Background: MIW815 (ADU-S100) is a novel synthetic cyclic dinucleotide that activates the STimulator of INterferon Genes (STING) pathway impacting tumor cells, tumor microenvironment, vasculature, tumor-associated fibroblasts, and priming APC and CD8+ T cells. Spartalizumab is a humanized IgG4 mAb that blocks the binding of PD-1 to PD-L1/2. Preclinical data support synergistic antitumor effects when MIW815 (ADU-S100) is combined with checkpoint inhibitors. Methods: In this Phase Ib dose escalation study, pts with advanced/metastatic solid tumors or lymphoma received MIW815 (ADU-S100) (intratumoral injections [50–800 µg] either weekly [3 weeks on/1 week off] or Q4W) and spartalizumab (400 mg IV Q4W). Injected and non-injected tumor biopsies were obtained at baseline and on treatment. Primary objectives are to determine safety and identify a dose/schedule for future studies. Preliminary activity, pharmacokinetics (PK), and pharmacodynamics (PD) are also being explored. Results: As of Jan 11, 2019, 66 pts (median age: 61 y) with various solid tumors or lymphomas have been treated. Treatment was discontinued in 49 pts (74%) due to disease progression (n = 28), pt/physician decision (n = 18), AE (n = 2), or death (n = 1). No DLTs were reported during the first cycle at any dose level. Most common (≥5 pts) treatment-related AEs (TRAEs) were injection site pain (12%), pyrexia (11%), and diarrhea (9%). Grade 3/4 TRAEs (in ≥2 pts) were increased AST and ALT (3% each). Serious TRAEs were pyrexia (3%), increased amylase, increased lipase, diarrhea, fatigue, hyperthyroidism, partial seizures, dyspnea, and pneumonitis (all 2%). Partial responses in pts with PD-1–naive TNBC and PD-1–relapsed/refractory melanoma have been observed. MIW815 (ADU-S100) plasma exposure generally increased in a dose-dependent manner with a rapid terminal half-life. Response data, PK and PD analyses will be presented. Conclusions: Thus far, MIW815 (ADU-S100) + spartalizumab has demonstrated antitumor activity in PD-1–naive TNBC and PD-1–relapsed/refractory melanoma. The combination is well tolerated, with no DLTs reported to date. The MTD has not been reached and dose escalation is ongoing. Clinical trial information: NCT03172936