This is quite important especially if you have a mismatch repair deficiency.
While anti-PD1 therapies are approved for mCRPC patients with high tumor mutational burden (TMB) or mismatch repair deficiency (dMMR), dual immune checkpoint blockade has been limited by toxicity concerns.
The INSPIRE trial enrolled 69 patients with mCRPC characterized by dMMR, high TMB (>7 mutations per megabase), BRCA2 mutations, or biallelic inactivation of CDK12. Patients received nivolumab (3 mg/kg) and ipilimumab (1 mg/kg) every three weeks for four cycles, followed by maintenance nivolumab therapy. The primary endpoint was the disease control rate exceeding six months.
The study met its primary endpoint, achieving a disease control rate over six months in 38% of patients, surpassing the target of 22%. Notably, patients with mismatch repair deficiency showed the most significant benefit, with an 81% disease control rate, a 75% objective response rate, and a median progression-free survival of 32.7 months. In contrast, limited efficacy was observed in patients with high TMB, CDK12 inactivation, and BRCA2 mutations.
Safety was a concern, as treatment-related adverse events led to permanent discontinuation in 20% of patients, and grade 3 or higher adverse events occurred in 48%, including diarrhea and elevated liver enzymes. There were two treatment-related deaths due to severe toxicity.
Screw Checkmate 650 - the “trials” of trials! 
Sudy shows Stereotactic Radiotherapy safe for treating oligometastases
Colchicine and Inflammation Revisited
