Abstract
Phase II study of spartalizumab (PDR001) and LAG525 in advanced solid tumors and hematologic malignancies
Journal of clinical oncology, Vol.37(15_suppl), pp.2553-2553
05/20/2019
DOI: 10.1200/JCO.2019.37.15_suppl.2553
Abstract
2553
Background: Spartalizumab and LAG525 are monoclonal antibodies targeting PD-1 and LAG-3, respectively. Dual blockade of PD-1 and LAG-3 has shown synergistic antitumor activity in preclinical models. Here we describe preliminary efficacy of spartalizumab + LAG525 across seven tumor types. Methods: Phase II, open-label, parallel-cohort study was conducted in pts with solid or hematologic malignances relapsed and/or refractory to standard-of-care therapies. Prior immunotherapy was prohibited. LAG525 (400 mg) and spartalizumab (300 mg) were dosed intravenously every 3 weeks. Primary endpoint was clinical benefit rate at 24 weeks (CBR24), assessed using a Bayesian hierarchical model-based futility analysis. Posterior probability that clinical benefit exceeds historical control (Pr) was estimated to determine futility at interim against prespecified thresholds. Results: As of January 7 2019, 76 pts received spartalizumab + LAG525; 72 pts were eligible for analysis (Table). The Pr cut-off for all arms was > 0.70. Hence, neuroendocrine tumors (NET), small cell lung cancer (SCLC) and diffuse large B-cell lymphoma (DLBCL) cohorts all met the expansion criteria with Pr of 0.971, 0.975 and 0.804 respectively. CBR24 were as follows; NET: 0.86, SCLC: 0.27, DLBCL: 0.43. Prostate, sarcoma and ovarian cohorts did not meet the expansion criterion (Pr > 0.70) but were not declared futile; enrollment was paused pending results of next analysis. Gastroesophageal (GE) cancer cohort was stopped for futility due to Pr (0.071) below the futility threshold. Conclusions: Spartalizumab and LAG525 showed promising activity in NET, SCLC and DLBCL that met expansion criteria. The GE cohort was declared futile. Remaining cohorts are paused pending further analysis. Clinical trial information: NCT03365791. [Table: see text]
Details
- Title: Subtitle
- Phase II study of spartalizumab (PDR001) and LAG525 in advanced solid tumors and hematologic malignancies
- Creators
- Nataliya Volodymyrivna Uboha - University of Wisconsin Carbone Cancer CenterMohammed M. Milhem - University of IowaChristina Kovacs - NovartisAlpesh Amin - NovartisAndrea Magley - NovartisD. Das Purkayastha - Novartis Pharmaceuticals Corporation, East Hanover, NJSarina Anne Piha-Paul - The University of Texas MD Anderson Cancer Center
- Resource Type
- Abstract
- Publication Details
- Journal of clinical oncology, Vol.37(15_suppl), pp.2553-2553
- DOI
- 10.1200/JCO.2019.37.15_suppl.2553
- ISSN
- 0732-183X
- eISSN
- 1527-7755
- Language
- English
- Date published
- 05/20/2019
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984363303302771
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