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

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.

1. 1. Kates M, et al. Eur Urol Oncol 2019; 2588-9311(19)30025-2.
   2. Lakhani N, et al. Phase I studies of Sym021, an anti-PD-1 antibody, alone and in combination with Sym022 (anti-LAG-3) or Sym023 (anti-TIM-3). ESMO 2020 Virtual Meeting, abstract 1019O.