Oncolytics Biotech Inc T.ONC

RE:RE:RE:RE:RE:Resistance to ADCs in the treatment of solid tumors

[Noteable]

Despite the strong preclinical rationale for ADC and ICI combination therapies, a major concern is the potential for overlapping toxicities. Specifically, T-DXd monotherapy is associated with around 15% incidence of pneumonitis (82), whereas ICI monotherapy shows a lower incidence 3%.

In the KATE2 trial, the addition of atezolizumab to T-DM1 in TNBC patients resulted in more toxicity, with 33% of patients experiencing serious adverse events. While no clinical benefit was observed in the intention-to-treat population, exploratory analyses suggest a potential benefit in patients with PD-L1–positive TNBC, highlighting the importance of identifying the specific patient subset that may derive benefit from this combination.

[ ONCY's pelareorep is particularly effective in PD-L1-negative patients, and is able to stimulate the immune system and remodel the TME in advance of immune checkpoint inhibitor being sequentially administered. ONCY's Phase 2 GOBLET -1 study using pelareorep in combination with atezolizumab has demonstrated clinical benefit using this strategy.] 

On the other hand, safety data from BEGONIA, which combined Dato-DXd and durvalumab in metastatic TNBC patients, noted no cases of pneumonitis. To achieve a balance between effectiveness and tolerability, combination ADC and ICI therapies need to optimize their payloads and dosing strategy, which may require sequential dosing or dose reductions, which a combination with ONCY's pelareorep appears capable of achieving.