Journal article
Phase Ib study of MIW815 (ADU-S100) in combination with spartalizumab (PDR001) in patients (pts) with advanced/metastatic solid tumors or lymphomas.
- Meric-Bernstam, Funda Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, TX;
- Sandhu, Shahneen Kaur Peter MacCallum Cancer Centre, The University of Melbourne, Melbourne, Australia;
- Hamid, Omid The Angeles Clinic and Research Institute, Los Angeles, CA;
- Spreafico, Anna Princess Margaret Hospital, Toronto, ON, Canada;
- Kasper, Stefan Department of Medical Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany;
- Dummer, Reinhard University of Zürich, Zürich, Switzerland;
- Shimizu, Toshio National Cancer Center Hospital (NCCH), Tokyo, Japan;
- Steeghs, Neeltje Netherlands Cancer Institute, Amsterdam, Netherlands;
- Lewis, Nancy Novartis Pharmaceuticals Corporation, East Hanover, NJ;
- Talluto, Craig C. Novartis Institutes for BioMedical Research, Cambridge, MA;
- Dolan, Sinead Novartis Institutes for BioMedical Research, Cambridge, MA;
- Bean, Andrew Novartis Pharmaceuticals Corporation, East Hanover, NJ;
- Brown, Robert Aduro Biotech Inc., Berkeley, CA;
- Trujillo, Damian Aduro Biotech Inc., Berkeley, CA;
- Nair, Nitya Aduro Biotech, Berkeley, CA;
- Luke, Jason J. The University of Chicago Medicine, Chicago, IL;
Published in:
- Journal of Clinical Oncology. - American Society of Clinical Oncology (ASCO). - 2019, vol. 37, no. 15_suppl, p. 2507-2507
English
2507 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.
- Language
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- English
- Open access status
- closed
- Identifiers
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- DOI 10.1200/jco.2019.37.15_suppl.2507
- ISSN 0732-183X
- Persistent URL
- https://folia.unifr.ch/global/documents/74366
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