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PD-(L)1, LAG-3, and TIM blockade

ESMO 2020
PD-(L)1 is not the only immune checkpoint inhibiting anti-cancer activity of the immune system. In particular, upregulation of LAG-3 and TIM have been associated with resistance to PD-(L)1 blockade [1]. In a first-in-human phase 1 trial, the anti-PD-1 antibody Sym021 was combined with either the anti-LAG-3 antibody Sym022 or the anti-TIM antibody Sym023 [2]. A total of 70 patients with a variety of heavily pretreated, advanced tumours was treated with either Sym021 monotherapy or one of the combinations at escalating doses up to 10-20 mg/kg every 2 week. Sym021 alone or in combination with Sym022 or Sym023 was well tolerated with an adverse event profile typical of immune checkpoint inhibitors. Anti-tumour activity was observed with either Sym021 alone or in combination. Further evaluation of the anti-tumour activity of the in select tumour types post-PD-(L)1 treatment is planned. Triplet (Sym021, Sym022, Sym023) dose escalation is ongoing.

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