Abstract:
The ERAP1 inhibitor GRWD5769 combined with cemiplimab, a PD-1 inhibitor, has shown preliminary promise in overcoming resistance to PD-(L)1 blockade by targeting antigen processing. Another resistance-mitigating strategy is potentially IOS-1002, an antagonist of two immunosuppressive receptors, LILRB1/2 and KIR3DL1, combined with anti-PD-1 pembrolizumab. As well, an update on the recently published DART (NCI/SWOG S1609) study indicates that the classic combination of ipilimumab with nivolumab may benefit even more rare cancers, including gestational trophoblastic neoplasia.
Insights
New strategies combining immunotherapy agents show promise in overcoming resistance to PD-(L)1 blockade and expanding treatment options for rare cancers.
Area of Science:
- Immunotherapy
- Oncology
- Cancer Research
Background:
- Resistance to PD-(L)1 blockade remains a significant challenge in cancer treatment.
- Targeting antigen processing and immunosuppressive pathways are potential strategies to overcome this resistance.
- The combination of ipilimumab and nivolumab has shown efficacy in various cancers.
Purpose of the Study:
- To explore novel combination immunotherapies for overcoming resistance to PD-(L)1 blockade.
- To evaluate the potential of targeting antigen processing and immunosuppressive receptors in combination with PD-1 inhibitors.
- To investigate the efficacy of ipilimumab and nivolumab in rare cancers.
Main Methods:
- Preclinical evaluation of ERAP1 inhibitor GRWD5769 with cemiplimab.
- Assessment of IOS-1002, an antagonist of LILRB1/2 and KIR3DL1, combined with pembrolizumab.
- Analysis of updated data from the DART (NCI/SWOG S1609) study on ipilimumab and nivolumab.
Main Results:
- GRWD5769 combined with cemiplimab shows preliminary promise in overcoming PD-(L)1 resistance.
- IOS-1002 in combination with pembrolizumab is being investigated as another resistance-mitigating strategy.
- The combination of ipilimumab and nivolumab may benefit rare cancers, including gestational trophoblastic neoplasia.
Conclusions:
- Combination immunotherapies targeting antigen processing or immunosuppressive receptors offer potential to overcome PD-(L)1 blockade resistance.
- The established ipilimumab and nivolumab combination may have broader applications in rare oncological conditions.
- Further research is warranted to validate these combination strategies in clinical settings.
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