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. 2025 May;21(11):1325-1331.
doi: 10.1080/14796694.2025.2485020. Epub 2025 Mar 28.

S2303: phase II/III trial of paclitaxel + ramucirumab ± nivolumab in gastric and esophageal adenocarcinoma (PARAMUNE)

Anwaar Saeed  1 , Sarah Colby  2 , Paul Eliezer Oberstein  3 , Dan G Duda  4 , Robin Park  5 , Rajiv Agarwal  6 , Colmar Figueroa-Moseley  7 , Riha Vaidya  2 , Joseph M Unger  2 , Katherine A Guthrie  2 , Flavio G Rocha  8 , Maheswari Senthil  9 , Rachael A Safyan  10 , Zev A Wainberg  11 , Syma Iqbal  12 , E Gabriela Chiorean  10 , Philip A Philip  13   14
Affiliations

S2303: phase II/III trial of paclitaxel + ramucirumab ± nivolumab in gastric and esophageal adenocarcinoma (PARAMUNE)

Anwaar Saeed et al. Future Oncol. 2025 May.

Abstract

NCT06203600.

Keywords: Immunotherapy; anti-programmed death-1; combined positive score; gastric, gastroesophageal junction, or esophageal cancer; paclitaxel; ramucirumab; vascular endothelial growth factor.

Plain language summary

Cancer of the stomach and esophagus is aggressive with poor patient outcomes. Historically, the treatment for such patients has involved the use of combined chemotherapy. In recent years, the addition of immunotherapy to the treatment of patients with advanced cancers of the stomach and esophagus has led to patients living longer with a longer period without tumor growth. However, whether continuing the immunotherapy after the tumor has grown while on treatment is beneficial or not is a question that has not been answered. The standard treatment after patients’ tumor has grown on their initial treatment involves a drug called ramucirumab, which blocks the ability of cancer cells to create abnormal blood vessels around itself to support its own growth. Recent research suggests that drugs like ramucirumab make immunotherapy more effective. To test whether continuing immunotherapy in combination with this “second-line” treatment that includes ramucirumab, we have designed a study to compare whether one group who will receive immunotherapy will live longer versus another group who will not receive immunotherapy.

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Conflict of interest statement

Anwaar Saeed reports consulting or advisory board role with AstraZeneca, Bristol-Myers Squibb, Merck, Exelixis, Pfizer, Xilio therapeutics, Taiho, Amgen, Autem therapeutics, KAHR medical, Arcus therapeutics, Regeneron, Replimune and Daiichi Sankyo; institutional research funding from AstraZeneca, Bristol-Myers Squibb, Merck, Clovis, Exelixis, Actuate therapeutics, Incyte Corporation, Daiichi Sankyo, Five prime therapeutics, Amgen, Innovent biologics, Dragonfly therapeutics, Oxford Biotherapeutics, Replimune, Phanes therapeutics, Arcus therapeutics, Regeneron and KAHR medical. Dan Duda reports receiving research grants from BMS, Exelixis, Surface Oncology, and Bayer. Riha Vaidya reports current employment at Flatiron Health. Flavio Rocha reports consultant for AZ and BetaGlue. Rachael A. Safyan reports institutional research funding from Replimune, Exelixis, and Verastem and consulting or advisory board from Mirati, Guardant, Agenus, Ipsen. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Figures

Figure 1.
Figure 1.
Vascular endothelial growth factor (VEGF) blockade may synergize with programmed-death or -ligand-1 inhibition via tumor immune microenvironment remodeling. Tumor hypoxia leads to the promotion of an immune suppressive tumor microenvironment (TME) in part due to HIF-1 alpha mediated activation of VEGF/ANG pathways that disrupt tumor vasculature. VEGFR blockade leads to enhanced activity of dendritic cells as well as inhibition of immune suppressor cells, such as regulatory T cells and myeloid-derived suppressor cells. PD-1/L1 blockade enhances T cell immunity and indirectly inhibits inhibitory tumor-associated macrophage activity. Abbreviations: VEGFR2, vascular endothelial growth factor receptor-2; PD-1/L1, programmed death-1/ligand-1; MDSC, myeloid-derived suppressor cell; TGF, transforming growth factor; IL, interleukin; TNF, tumor necrosis factor; M-CSF, macrophage-colony stimulating factor; treg, regulatory T cells. Created in BioRender. Park, R. (2025).
Figure 2.
Figure 2.
Trial schema. This is a randomized phase II/III study comparing the efficacy of nivolumab combined with paclitaxel and ramucirumab to paclitaxel and ramucirumab (standard of care) in previously treated advanced G/GEJ/E cancer.
See this image and copyright information in PMC

References

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