The bispecific antibody Ivanesimab binds to the VEGF dimer, creating a "daisy chain" of antibody-VEGF complexes. This multimerization concentrates the drug in the tumor microenvironment, where VEGF is high, and enhances its ability to bind and block PD-1 more effectively than single-molecule approaches.
Subtle, early signs of serious T-cell engager toxicities like CRS and ICANS (e.g., mild confusion, headache) can be easily dismissed by patients. Effective management requires educating patients to report these symptoms immediately, as delaying can lead to severe outcomes, shifting focus to proactive patient behavior modification.
Small cell lung cancer tumors are immunologically "cold" with few T-cells, limiting standard immunotherapy efficacy. Tarlatumab, a BiTE, physically links T-cells to tumor cells via the DLL-3 target, forcing an immune synapse and helping the immune system attack a tumor it would otherwise ignore.
In the HARMONY A study, Ivanesimab plus chemotherapy significantly improved progression-free survival in EGFR-mutant non-small cell lung cancer patients. This is notable because prior trials showed that adding standard PD-1 inhibitors to chemotherapy was ineffective for this specific patient population.
The HARMONY-2 study showed Ivanesimab delivered a median progression-free survival of 11.3 months compared to 5.8 months for Pembrolizumab in PD-L1 positive NSCLC. Analysis confirmed Pembrolizumab performed as expected, suggesting the dual VEGF/PD-1 blockade provides a genuinely superior clinical benefit over PD-1 inhibition alone.