Dr Klempner on the Safety Profile of Givastomig Plus Nivolumab and mFOLFOX6 in Gastric, Esophageal, and GEJ Cancer

“The main drug-related adverse effects attributed to givastomig were infusion-related reactions, which are manageable, and some nausea and vomiting, which were reported in [approximately] 50% and 35% of patients, respectively.”

Samuel J. Klempner, MD, a gastrointestinal medical oncologist at Massachusetts General Hospital, detailed the safety profile of givastomig plus nivolumab (Opdivo) and mFOLFOX6 (leucovorin, fluorouracil [5-FU], and oxaliplatin) for the treatment of patients with HER2-negative, Claudin 18.2 (CLDN18.2)–positive gastric, esophageal, or gastroesophageal junction adenocarcinoma.

Patients in the phase 1b study (NCT04900818) treated with the combination of givastomig, nivolumab, and mFOLFOX6 did not experience any dose-limiting toxicities, Klempner began. He noted that the main treatment-related adverse effects (TRAEs) that were associated with givastomig included infusion-related reactions that were manageable. Additionally, nausea and vomiting were also observed in 53% and 35% of patients, respectively, he said. These rates of TRAEs were lower than those with zolbetuximab-clzb (Vyloy), although consistent with the class effect that is observed with most CLDN18.2-directed approaches, which is often associated with nausea and vomiting, he explained.

Furthermore, there were no significant liver function abnormalities, Klempner added. One patient treated with the 5 mg/kg dose of the givastomig, nivolumab, and mFOLFOX6 combination had grade 3 aspartate aminotransferase and alanine transaminase level elevations, he stated. However, he emphasized that the respective patient had significant underlying comorbidities with hepatic disease burden. Previously, intravenous 4-1BB antibodies were plagued by significant hepatotoxicity, according to Klempner. Nevertheless, givastomig lead to conditional activation of 4-1BB only in the tumor microenvironment in dose escalation and does not currently display a similar signal for hepatotoxicity, he asserted. Other toxicities were consistent with previously known profiles for chemotherapy with PD-1 agents, he stated.

The study included 3 cohorts in the dose-escalation portion of the study, which included the givastomig at doses of 5 mg/kg (n = 5), 8 mg/kg (n = 6), and 12 mg/kg (n = 6).