Abstract 1497TiP
Background
Improving immunotherapy efficacy remains a large unmet need in esophagogastric cancer (EGC). Combining radiation therapy with immunotherapy represents a promising strategy, as radiation has been shown to augment T cell priming, trafficking, and effector responses within the tumor. Radiation can also enhance immunogenic cell death, potentially sensitizing otherwise non-inflamed tumors to anti-PD-1 therapy. We have shown that multiple checkpoints, including LAG-3, are upregulated in human samples pre and post chemo-radiation in esophageal cancer. In this study, we aim to investigate whether stereotactic body radiation therapy (SBRT) can enhance the effectiveness of anti-PD1 +/- anti-LAG-3 (relatlimab) immunotherapy by decreasing tumor bulk and altering the tumor microenvironment.
Trial design
This is a phase Ib single-arm, open-label pilot study (NCT03610711) in adult patients with recurrent or advanced EGC and are anti-PD-(L)1 therapy naive. This study aims to enroll 30 patients (15 patients in Arm A, then 15 patients in Arm B). Patients will receive SBRT 8Gy x 3 to one or more tumor lesions, followed by systemic therapy with nivolumab (Arm A) or nivolumab + relatlimab (Arm B) every 4 weeks until disease progression. A target lesion will be left un-radiated to enable correlative analyses. This lesion will biopsied prior to treatment and approximately 4 weeks later (after completion of radiation to the other metastatic sites and after 1 cycle of nivolumab +/- relatlimab). The primary objective of the study is to evaluate changes in infiltrating CD8+ T cell density pre and post treatment in a non-irradiated metastatic lesion. Key secondary and exploratory endpoints include safety, PFS, OS, and comprehensive correlative analyses of the tumor-specific T cell repertoire. Recruitment for this study began in March 2019, but was limited to oligometastatic EGC patients. Eligibility was recently expanded in March 2020 to allow polymetastatic patients. The study is actively enrolling and is funded by BMS.
Clinical trial identification
NCT03610711.
Editorial acknowledgement
Legal entity responsible for the study
Johns Hopkins.
Funding
Bristol-Myers Squibb.
Disclosure
V.K. Lam: Advisory/Consultancy: Takeda; Research grant/Funding (institution): BMS. C. Hu: Research grant/Funding (self): NCI; Research grant/Funding (self): RTOG; Advisory/Consultancy: Merck. R.J. Kelly: Advisory/Consultancy: BMS; Advisory/Consultancy: Novartis; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Pieris Pharmaceuticals; Advisory/Consultancy: Astellas; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Takeda; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Eli Lilly. All other authors have declared no conflicts of interest.