RE:RE:Resistance to ADCs in the treatment of solid tumors ADC and checkpoint inhibitors can enhance T-cell infiltration to the tumour microenvironment and boost antitumour immunity, however a number of clinical trials that look at the doublet comprised of ADCs in combination with immune checkpoint inhibitors have had mixed results.
The KATE2 study (NCT02924883) found that combining the checkpoint inhibitor atezolizumab with the ADC trastuzumab emtansine (Kadcyla) (T-DM1) offered no significant survival benefits in HER2-positive breast cancer patients and led to higher toxicity, causing the trial to end early. Another trial (NCT03032107) showed moderate efficacy for T-DM1 and pembrolizumab. However, a phase 1b study (NCT03523572) pairing trastuzumab deruxtecan (T-DXd) with nivolumab did not meet the higher efficacy benchmarks set by T-DXd alone, despite substantial response rates.Meanwhile, the BEGONIA trial (NCT03742102), which is ongoing and assessing various combinations of the PD-L1 inhibitor durvalumab (Imfinzi), demonstrated the ADC datopotamab deruxtecan (Dato-DXd), paired with durvalumab, demonstrated strong activity, regardless of PD-L1 expression.
These findings once again show that the addition of ONCY's pelareorep can be a vital addition for an effective ADC + checkpoint inhibitor I/O combination and beneficial clinical outcome.
By "priming" the immune system and remodeling the TME in advance of the addition anti-PD-(L)1 antibody treatment, pelareorep is able to synergistically combine with immune checkpoint inhibitors (ICI) ... making ONCY's pelareorep a critical facilitator to any proposed ADC / ICI combination,.