First-in-human study of ZGGS15, a dual-specific antibody targeting LAG-3 and TIGIT, as monotherapy in patients with advanced solid tumors.

2641 Background: ZGGS15 is a novel humanized bispecific antibody of anti LAG-3 and TIGIT. It could reverse Treg inhibition of T cells and NK cells, and kills tumor cells by restoring the function of T cells and NK cells. In non-clinical studies, ZGGS15 showed synergistic anti-tumor effects with the anti-PD-1 antibody. We conducted a Phase 1 dose escalation and expansion study to assess tolerability, safety, and efficacy of ZGGS15 as monotherapy in patients with advanced solid tumors. Methods: In the dose-escalation phase, a standard "3+3" design, with an accelerated titration for the starting dose. Total of 6 dose levels, from 0.3 to 30 (0.3, 1, 3, 10, 20, 30) mg/kg administered by the intravenous infusion, once every three weeks, in patients with advanced solid tumors who had failed to the available standard treatments. The first treatment cycle (21 days) was defined as the dose-limiting toxicity (DLT) observation period. The study assessments included tolerability, safety, preliminary efficacy, etc. and tumor responses were assessed by RECIST1.1 and iRECIST criteria. Results: As January 8 2025, a total of 22 patients (9 males and 13 females), with a median age of 59 years, participated in the dose escalation from 0.3 to 30 mg/kg and completed the DLT observation. Of the 22 patients, 11 (50.0%) received at least 3 prior lines of therapies, and eight (36.4%) had previously treated with PD-1 or PD-L1 inhibitors. No DLT events were observed. TRAEs occurred in 20 (90.1%) patients, with only one patient (4.5%) experienced a Grade 3 TRAE of lymphocyte count decreased, and no Grades 4 or 5 TRAEs were reported. Among the 17 patients who had at least one post-baseline tumor scan, six had achieved stable disease (SD) with a disease control rate (DCR) of 35.3%. In the subgroup of 8 patients with lung adenocarcinoma, 5 (62.5%) had achieved SD, including two patients who had ≥ 2 prior lines of treatments and maintained SD over 36 weeks. Conclusions: The results showed that ZGGS15 was well tolerated and had a very good safety profile. It is anticipated that when in combination with other anti-cancer therapies, e.g., an anti-PD-1 or PD-L1 antibody, for advanced solid tumors, ZGGS15 may provide synergistic anti-tumor effects and further enhance treatment benefits. Clinical trial information: NCT05864573 .