Good, broad review, includes IO and non-IO combos. One salient point only mentioned in regards to IO combination of anti-PD1 and OX40 is sequencing/order. As noted, many chemo combinations have little science behind them, and especially lacking here as well is dosing and sequence effects.
Even when researchers think they have a solid hypothesis for a two-drug combination, biology can throw them for a loop. One cautionary tale is that of an anti-PD-1 antibody plus an OX40 agonist that stimulates the proliferation and expansion of T cells. Two recent studies, from Bernard Fox’s group at Oregon Health & Science University’s Knight Cancer Institute and Khleif’s lab at Augusta University, demonstrated that while, on paper, the combination should have been at least twice as effective in stimulating T cells as either treatment alone, it instead caused T cells to die in several mouse models of various tumor types.... As it turned out, the researchers were able to produce a synergistic effect, compared to an anti-PD-1 antibody alone, but only by giving the mice the OX40 antibody first, then treating them with the anti-PD-1 a few days later...