Tovecimig (CTX-009)

No prescribing information, boxed warning, contraindication, or risk evaluation and mitigation strategy exists, because tovecimig is investigational. In COMPANION-002, the most common treatment-emergent adverse events in the tovecimig combination arm were hypertension (69%) and fatigue (67%), and the most common related treatment-emergent adverse events of grade 3 or higher were hypertension (44%) and neutropenia (36%). In the single-arm phase 2 study of tovecimig plus paclitaxel in South Korea, all 24 participants had at least one treatment-emergent adverse event and grade 3 or higher events were reported in 95.8%, including decreased neutrophil count in 83.3%, anemia in 20.8%, hypertension in 16.7% and decreased platelet count in 12.5%; grade 3 or higher adverse events of special interest were hemoptysis or hemorrhage in 12.5% and gastrointestinal or tumor perforation in 8.3%, with no pulmonary hypertension, wound healing complication or cardiac failure. In the phase 1 monotherapy dose escalation study of 45 participants, the most frequent treatment-emergent adverse events were hypertension (37.8%), headache (22.2%), asthenia (13.3%), anemia (13.3%) and fatigue (11.1%), no dose-limiting toxicity occurred, and the maximum tolerated dose was not reached at 17.5 mg/kg. In the phase 2 monotherapy study in colorectal cancer, hypertension was the most common treatment-emergent adverse event and occurred only in participants with a prior history of hypertension. An independent data safety monitoring committee reviewed COMPANION-002 safety data at four prespecified meetings and recommended continuation without modification each time. Adverse events reported with other DLL4 and VEGF bispecific antibodies include pulmonary hypertension and gastrointestinal perforation.