Sacituzumab govitecan
Another ADC being tested with PD-1/PD-L1 inhibitors is sacituzumab govitecan (Trodelvy, Gilead), which has already received FDA approval for metastatic triple-negative breast cancer, pretreated HR+/HER2- metastatic breast cancer, and metastatic urothelial cancer. Like datopotamab, sacituzumab targets TROP-2. Researchers reported preliminary results from the phase 2 EVOKE-02 study, in which the ADC was combined with pembrolizumab for the first-line treatment of metastatic NSCLC. The overall response rate was 56% (95% CI, 42%-69%). Among patients with PD-L1 tumor proportion score (TPS) ≥ 50%, the ORR was 69% (95% CI, 49%-85%) and 44% (95% CI, 26%-62%) among those with TPS < 50%. The disease control rate was 86% (95% CI, 68%-96%) and 78% (95% CI, 60%-91%), respectively. The most frequent treatment-emergent adverse events (TEAEs) were diarrhea, anemia, and asthenia, and 18% of patients discontinued the study drug because of TEAEs. (Abstract)
Ifinatamab deruxtecan
Ifinatamab deruxtecan (Daiichi Sankyo) targets the B7-H3 antigen, which is an immunoregulatory protein that is overexpressed in many tumors. In the DS7300-A-J101 study, it was tested in patients with advanced or metastatic solid tumors, without selection for B7-H3 expression. A subgroup analysis of 22 patients with small cell lung cancer (SCLC) showed an ORR of 52.4 (95% CI, 29.8-74.3), a complete response of 4.8%, and a partial response in 47.6%. The median PFS was 5.6 months (95% CI, 3.9-8.1) and median OS was 12.2 months (95% CI, 6.4-not applicable). The most common treatment-emergent adverse events were nausea (59.1%), fatigue (50.0%), anemia (27.3%), vomiting (27.3%), and decreased appetite (22.7%). (Abstract)