1527TiP CONGRATS-combination of nivolumab plus relatlimab in patients with advanced or metastatic soft-tissue sarcoma: A proof-of-concept randomized phase II study

Despite optimal treatment, up to 40% of patients with soft-tissue sarcomas (STS) will develop metastatic disease. In this setting, the standard of care is based on palliative chemotherapy with a median survival of only 18 months. Innovative treatments are therefore urgently needed in this setting. Our group has recently shown that STS characterized by the presence of intratumoral tertiary lymphoid structures (TLSs) are particularly sensitive to immune-checkpoint inhibitors (Italiano et al Nature Medicine 2022, In Press). We and others have also shown a strong upregulation of LAG3 in TLS-positive STS which prevent the onset of autoimmunity. Altogether, these findings suggest that simultaneously inhibiting PD1 and LAG3 could lead to a better clinical benefit in inflamed STS. CONGRATS is a multicentric, randomized non-comparative, open-label, two-arm phase 2 trial investigating the efficacy of nivolumab in association with relatlimab in patients with advanced STS with presence of tertiary lymphoid structures (assessed centrally). This study will randomize ∼67 patients with one patient randomized in experimental arm (nivolumab + relatlimab) for one patient randomized in standard arm (nivolumab alone). Eligible patients must have unresectable or metastatic, no standard treatment options available or a contraindication to standard treatment options, and ECOG PS 0–1. Patients with prior exposure to PD1/PDL1 or LAG-3 agonist are excluded. Nivolumab will be administered IV at the dose of 240 mg on days 1 and 15 every 4 weeks. Relatlimab will be administered IV at the dose of 80 mg on days 1 and 15 every 4 weeks. The primary endpoint, assessed independently for each arm, is progression-free rate at 6 months as per RECIST 1.1. Secondary endpoints include adverse events (AEs)/serious AEs, progression-free and overall survivals. Pharmacodynamic and biomarkers will be explored. The first patient received study drug on April 21, 2020. This research is supported by Bristol-Myers Squibb International Corporation. NCT04095208, September 19, 2019. Institut Bergonié, Bordeaux. Bristol-Myers Squibb International Corporation.