Dr Klempner on Data for Givastomig Plus Nivolumab/mFOLFOX in Metastatic Gastric, Esophageal, and GEJ Adenocarcinoma

"The toxicity profile appears to be manageable [with the combination], and the 8-mg/kg and 12-mg/kg cohorts [for givastomig] have shown a very encouraging [efficacy] signal in a small number of patients. We're very excited to await the expansion cohort [results] and see if this encouraging signal holds in larger patient numbers."

Samuel J. Klempner, MD, a gastrointestinal medical oncologist at Massachusetts General Hospital Cancer Center and associate professor of medicine at Harvard Medical School, detailed preliminary safety and efficacy findings from a phase 1b trial (NCT04900818) evaluating the bispecific antibody givastomig in combination with nivolumab (Opdivo) and modified FOLFOX (mFOLFOX) in patients with metastatic gastric, esophageal, or gastroesophageal junction (GEJ) adenocarcinoma.

Data shared during a presentation at the 2025 ESMO Gastrointestinal Cancers Congress showed that givastomig, which targets Claudin 18.2 (CLDN18.2) and 4-1BB, elicited an objective response rate (ORR) of 71% in patients treated with givastomig at doses of 5 mg/kg, 8 mg/kg, or 12 mg/kg (n = 17). Notably, responses were observed irrespective of PD-L1 combined positive score or CLDN18.2 expression. At a median follow-up of 9.0 months, the 6-month progression-free survival (PFS) rate was 72.9% (95% CI, 42.6%-89.0%). The median PFS and duration of response were both not evaluable.

Notably, in a particularly difficult-to-treat subset of patients with both low PD-L1 and low CLDN18.2 expression, the ORR was 75% (n = 4), highlighting preliminary efficacy in biomarker-low populations.

The safety profile of givastomig plus nivolumab and mFOLFOX appeared manageable across the 3 tested dose levels. No dose-limiting toxicities were reported in any patients. Treatment-related adverse effects led to dose interruptions and treatment discontinuation in 24% and 12% of patients, respectively. Klempner reported that dose-dependent pharmacokinetics and induction of soluble 4-1BB were consistent with prior monotherapy findings, supporting target engagement.