Phase 1b/2 intratumoral 2141-V11 CD40 agonist added to ongoing first-line PD-1 therapy in gastroesophageal adenocarcinoma

Memorial Sloan Kettering Cancer Center is running this Phase 1b/2, open-label study testing intratumoral 2141-V11, a CD40 agonist antibody, added to ongoing anti–PD-1 therapy with or without 5-FU in advanced unresectable or metastatic esophageal, gastric, or gastroesophageal junction adenocarcinoma. Patients must already have received first-line fluoropyrimidine + anti–PD-1 therapy for 3–9 months; the platinum component of their initial regimen must be stopped before 2141-V11 begins. The intact primary tumor must remain accessible by endoscopy for direct injection. The safety lead-in evaluates 2141-V11 with nivolumab + 5-FU before expansion, with the goal of determining whether localized CD40 activation can stimulate antigen-presenting cells and strengthen the systemic immune response while patients continue PD-1–based treatment. The scientific angle is therefore not second-line salvage, but first-line treatment intensification after the initial platinum-containing phase, using intratumoral immune activation to potentially deepen or prolong disease control.