On April 12, 2021 Antengene Corporation Limited ("Antengene", SEHK: 6996.HK), a leading innovative biopharmaceutical company dedicated to discovering, developing, and commercializing global first-in-class and/or best-in-class therapeutics in hematology and oncology, reported preclinical data at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021, which demonstrated the synergistic effect of the combination of ATG-010 (selinexor, XPO1 inhibitor) and ATG-008 (onatasertib, mTORC1/2 inhibitor) for the treatment of triple-hit diffuse large B-cell lymphoma (DLBCL) (Press release, Antengene, APR 12, 2021, View Source [SID1234577937]).

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#1380: Synergistic effect of the combination of XPO1 and mTORC1/2 inhibition for the treatment of triple-hit DLBCL
Results from this study demonstrated potent in vitro and in vivo anti-tumor efficacy and synergy with the combination of ATG-010 and ATG-008, including strong synergistic activities in the triple-hit DLBCL cell line. Meanwhile, in the DLBCL circulating tumor cell-derived explants (CDX) model, the combination of ATG-010 and ATG-008 also showed enhanced tumor growth inhibition and synergism.

The single agent oral XPO1 inhibitor, ATG-010, is a first-in-class and only-in-class selective inhibitor of nuclear export (SINE) compound, approved by the US Food and Drug Administration (FDA) for the treatment of patients with DLBCL after at least two prior therapies. ATG-008 is a dual mTORC1/2 kinase inhibitor, which has shown preclinical and clinical activity in treating DLBCL. Antengene is currently developing a clinical study to investigate the combination of ATG-010 and ATG-008 in relapsed or refractory DLBCL (the MATCH trial).

The preclinical data showed:

ATG-008 and ATG-010 both inhibit the growth of the DLBCL cell line in vitro.
ATG-008 combined with ATG-010 enhanced the growth inhibition of triple-hit DLBCL cells.
ATG-008 combined with ATG-010 showed in vitro synergism in triple-hit DLBCL cells.
ATG-008 combined with ATG-010 showed in vivo synergism in CDX of the triple-hit DLBCL cell line.
Dr. Jay Mei, Founder, Chairman and CEO of Antengene, commented: "ATG-010 has been approved for the treatment of relapsed or refractory DLBCL, whilst ATG-008 has shown early clinical activity in the same disease. Using in vitro and in vivo DLBCL models, we found that ATG-010 combined with ATG-008 at certain concentrations could achieve amplified anti-tumor activity in triple-hit DLBCL. The strong synergism of the ATG-010 plus ATG-008 combination suggests a promising therapeutic strategy for the treatment of patients with DLBCL, including triple-hit disease where significant unmet medical needs exist, that we are looking forward to exploring in the MATCH trial."