A Study of Novel Agents or Combinations as Perioperative Treatment in Participants With Locally Advanced Resectable Gastroesophageal Adenocarcinoma

The film gives the main points. The full list below is copied from the registry; the study team makes the final decision.

• Age18 Years to no maximum
• SexAll
• Healthy volunteersNo

You may be able to join if

• Histologically documented gastric, GEJ, or esophageal adenocarcinoma with resectable disease
• Participants who are CLDN18.2-positive in Sub-study 1 or HER2-positive in Sub-study 2; no specific requirements for Sub-study 3
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate organ and bone marrow function
• Body weight > 35 kg

You cannot join if

• Participants had any prior anti-cancer treatment or surgery for the current gastric, GEJ, or esophageal cancer.
• Active or prior documented autoimmune or inflammatory disorders requiring systemic treatment with steroids or other immunosuppressive treatment
• Central nervous system (CNS) pathology
• Uncontrolled infections
• Participants with history of (non-infectious) interstitial lung disease (ILD)/pneumonitis, current ILD/pneumonitis, or suspected ILD/pneumonitis
• History of another primary malignancy
• Participants with any known or suspicious distant metastasis
• Uncontrolled hepatitis B and/or chronic or active hepatitis B
• Current or prior use of immunosuppressive medication within 14 days before the first dose of study intervention

This is how the treatment is meant to work. Whether it helps, and how safe it is, is what this trial is testing.

rilvegostomig. A bispecific antibody directed against the negative immunoregulatory human cell receptor programmed cell death protein 1 (PD-1; PDCD1; CD279) and the co-inhibitory molecule and immune checkpoint inhibitor T-cell immunoreceptor with immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibitory motif (ITIM) domains (TIGIT), with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, rilvegostomig simultaneously targets, binds to and inhibits PD-1 and TIGIT and their downstream signaling pathways. Inhibition of PD-1-mediated signaling may restore immune function through the activation of T-cells and T-cell-mediated immune responses. Inhibition of TIGIT expressed on various immune cells, particularly on tumor-infiltrating lymphocytes (TILs), prevents the interaction of TIGIT with its ligands CD112 (nectin-2; poliovirus receptor related-2; PRR2; PVRL2) and CD155 (poliovirus receptor; PVR; nectin-like protein 5; NECL-5). This enhances the interaction of CD112 and CD155 with the costimulatory receptor CD226 (DNAX Accessory molecule-1; DNAM-1), which is expressed on immune cells, such as natural killer (NK) cells and CD8+ T cells. This leads to CD226 dimerization and CD226-mediated signaling and activates the immune system to exert a T-cell-mediated immune response against cancer cells. PD-1, a transmembrane protein in the immunoglobulin superfamily (IgSF) expressed on T cells, functions as an immune checkpoint that negatively regulates T-cell activation and effector function when activated by its ligands programmed cell death-1 ligand 1 (PD-L1) or 2 (PD-L2); it plays an important role in tumor evasion from host immunity. TIGIT, a member of the Ig super family (IgSF) and an immune inhibitory receptor, plays a key role in the suppression of T-cell proliferation and activation; it is involved in tumor cell immune evasion, and the inhibition of antiviral immune responses. NCI Drug Dictionary

Treatments listed in the registry

• Sonesitatug Vedotin (Drug): Sonesitatug Vedotin will be administered as an IV infusion.
• Rilvegostomig (Drug): Rilvegostomig will be administered as an IV infusion.
• Trastuzumab Deruxtecan (T-DXd) (Drug): T-DXd will be administered as an IV infusion.
• Capecitabine (Drug): Capecitabine (Fluoropyrimidine) will be administered orally as chemotherapy standard of care.
• 5-Fluorouracil (5-FU) (Drug): 5-FU (Fluoropyrimidine) will be administered as a continuous IV infusion as chemotherapy standard of care.
• FLOT Chemotherapy (Drug): FLOT (5-FU, leucovorin, oxaliplatin, and docetaxel) Chemotherapy will be administered as an IV infusion.
• Calcium folinate (Drug): Calcium folinate will be administered as an IV infusion as chemotherapy standard of care.

Non Randomized · Parallel · masking: None

As the registry describes them. Requirements to join, such as a tissue sample, are in the eligibility list above even when on-study procedures are optional. Ask the study team which steps apply to you.

• surgery: Part of the study plan

Main goals

• Number of participants with adverse events (AEs) and serious adverse events (SAEs) (Until sub-study completion, up to 38 months)
• Percentage of participants with pathological complete response (pCR) (Until sub-study completion, up to 38 months)

Other goals

• Surgery completion rate
• R0 resection (complete resection) rate
• Percentage of participants with tumor downstaging
• Event-free survival (EFS)
• Disease-free survival (DFS)
• Objective response rate (ORR)
• Overall survival (OS)
• Serum concentrations of study interventions
• Number of participants with positive anti-drug antibodies (ADA)

Planned enrollment: 100 (estimated).

• Research Site, Newark, Delaware
• Research Site, Washington D.C., District of Columbia
• Research Site, Fairway, Kansas
• Research Site, North Shores, Michigan
• Research Site, Pittsburgh, Pennsylvania

49 recruiting sites outside the US. Site status as of Oct 30, 2026. Check the live record before contacting a site.

• ClinicalTrials.gov NCT07069712
• NCI Drug Dictionary: C188211

Registry record reviewed as fetched Oct 30, 2026, last updated by the sponsor Oct 15, 2026. Public record; not medical advice.