Multinational phase 1 trial of tobemstomig, a PD1-LAG3 bispecific antibody, in patients with ICI-experienced melanoma

The IgG1-based bispecific antibody tobemstomig simultaneously targets and blocks PD-1 and LAG-3 expressed on activated T-cells. A multinational phase 1 trial evaluated tobemstomig in three tumor-specific cohorts, enrolling ICI-experienced patients with melanoma or non-small cell lung cancer (NSCLC) and ICI-naïve patients with esophageal squamous cell carcinoma (ESCC). The dose escalation part of the trial included 35 patients and the extension part included 69 patients. Tobemstomig was well-tolerated up to the highest tested dose of 2100 mg every two weeks. The maximum tolerated dose was not reached, and 2100 mg Q2W was established as the recommended dose for expansion. Tobemstomig exhibited linear pharmacokinetics across the studied dose range. Partial responses were achieved by 2 of 4 patients (600 mg) and 4 of 13 patients (2100 mg) during dose escalation; 6 of 41 ICI-experienced melanoma patients (ORR 15%; 95% CI6.6-26.9) and 1 of 8 ICI naïve ESCC patients (ORR 12.5%; 90% CI 0.6-47.1). Proof-of-mechanism was demonstrated in ICI-experienced melanoma patients based on increases in the amounts of CD8+ T cells, expansion of stem-like CD8+ T cells, and the acquisition of cytotoxic effector functions, with limited changes in the Treg compartment. The authors conclude that tobemstomig had a tolerable and manageable safety profile across various advanced solid tumor indications.