At the European Society for Medical Oncology (ESMO) 2026, ABL Bio (298380) showcased the varying stages and clinical outcomes of its three leading bispecific antibody candidates. Tovesmirig, the most advanced candidate, a treatment for biliary tract cancer, demonstrated significant improvements in objective response rate (ORR) and progression-free survival (PFS). However, it failed to confirm a statistical improvement in overall survival (OS), a key hurdle in its U.S. regulatory approval process.
Givastomig, currently under development for gastroesophageal cancer, is accelerating toward Phase 3 trials after demonstrating tumor reduction in patients with low target expression—a group typically ineligible for existing targeted therapies. Meanwhile, data for ragistomig suggested a potential path to reducing severe adverse events by adjusting dosing intervals.
Tovesmirig: Promising Secondary Endpoints vs. OS Hurdles
The results of the COMPANION-002 Phase 2/3 study for tovesmirig, presented on the 24th by U.S. partner Compass Therapeutics, involved 168 patients with advanced biliary tract cancer. The combination of tovesmirig and paclitaxel yielded an ORR of 18.0%, compared to 5.3% for paclitaxel alone. The median PFS reached 4.7 months versus 2.6 months for the control group, representing a 56% reduction in the risk of disease progression or death.
While the study met its primary endpoint of ORR and key secondary endpoint of PFS, the median overall survival (OS) showed no significant difference—8.9 months for the combination group versus 9.4 months for the control. A notable factor in these results was the high crossover rate, where 54% of patients in the control group switched to the tovesmirig combination after disease progression.
Although Compass Therapeutics maintains its intent to pursue regulatory filing based on existing data, the U.S. Food and Drug Administration (FDA) recommended additional clinical trials to substantiate survival benefits last September. The timeline for both the drug's approval and ABL Bio’s future milestone payments hinges on the outcomes of ongoing negotiations with the FDA.
Givastomig: Targeting Low-Expression Patients for Phase 3
Givastomig (ABL111), a bispecific antibody targeting Claudin 18.2 and 4-1BB, demonstrated robust efficacy in a Phase 1b expansion study involving 71 patients. In the 8mg/kg cohort, the ORR reached 79%. Crucially, the drug showed tumor reduction in 75% of patients (9 out of 12) with low Claudin 18.2 expression (1–74%).
If successful in subsequent trials, givastomig could emerge as a vital treatment option for patients who do not meet the stringent 75% expression threshold required for currently approved therapies. ABL Bio and its co-developer, I-Mab (formerly NovaBridge), are currently conducting global Phase 2 trials and have completed discussions with the FDA regarding the design of a pivotal Phase 3 study.
Ragistomig: Dose Adjustment to Mitigate Toxicity
For ragistomig (ABL503), an immunotherapy targeting PD-L1 and 4-1BB, a Phase 1 study presented on the 23rd showed that extending the dosing interval from two weeks to six weeks significantly lowered the incidence of Grade 3 or higher treatment-related adverse events. The rate dropped from 51.6% to 26.2%, and severe liver toxicity markers also declined significantly. Despite the longer intervals, the drug maintained its anti-tumor activity. ABL Bio is now evaluating the candidate in combination with PD-1 inhibitors to see if this safety profile persists in a broader clinical setting.
[SOURCE] Title: [ESMO 2026 Analysis] ABL Bio’s New Drug Report Card: Regulatory Hurdles and Phase 3 Preparations
