Abstract 1525TiP
Background
Despite optimal surgery, up to 40% of patients with retroperitoneal sarcomas (RPS) will develop locoregional and/or distant relapse. Peri-operative radiotherapy has failed to improve outcome of these patients (Bonvalot et al Lancet Oncol 2020). Innovative strategies are urgently needed in this setting. Recent studies have shown the positive impact on overall survival of neoadjuvant systemic therapy in high-risk soft-tissue sarcoma (STS) of the extremities or trunk wall (Issels et al Lancet Oncol 2010; Gronchi et al Lancet Oncol 2017). Our group has recently shown that STS characterized by the presence of intratumoural tertiary lymphoid structures (TLSs) are particularly sensitive to immune-checkpoint inhibitors (Italiano et al Nature Medicine 2022, In Press). Altogether, these findings pave the way for precision medicine studies assessing the impact of neoadjuvant chemotherapy and immunotherapy in RPS selected based on micro-environment features.
Trial design
TORNADO is a multicentric, randomized non-comparative, open-label, two-arm phase 2 trial investigating retifanlimab with neoadjuvant chemotherapy in patients with selected RPS: grade 2/3 STS with presence of tertiary lymphoid structures (assessed centrally). This study will randomize ∼66 patients with one patient in experimental arm (doxorubicin + ifosfamide + retifanlimab) for one patient in standard arm (doxorubicin + ifosfamide). Eligible patients must have non-metastatic resectable disease without any prior treatment and ECOG 0-1. Neoadjuvant chemotherapy will be based on up to 3, 21-day cycles. Retifanlimab is given IV (375 mg) on day 1 every 3 cycle. Doxorubicin and ifosfamide are given IV respectively at 60 mg/m2 on day 1 and 9 g/m2 over three days, every cycle. In both arms, neoadjuvant chemotherapy will be followed by surgery. The primary endpoint is histological response defined as less than 10% of viable tumor cells on surgical sample. Secondary endpoints include toxicity, progression-free and overall survivals. Pharmacodynamic and biomarkers will be explored. The study is open to recruitment and is conducted with the support of Incyte International Sarl.
Clinical trial identification
NCT04968106.
Editorial acknowledgement
Legal entity responsible for the study
Institut Bergonié, Bordeaux.
Funding
Incyte International Sarl.
Disclosure
A. Italiano: Financial Interests, Personal, Advisory Board: Bayer, Roche, Philips, Chugai, GSK; Financial Interests, Institutional, Invited Speaker: Bayer, AstraZeneca, Roche, MSD, Ipsen, Merck. M. Brahmi: Financial Interests, Personal, Invited Speaker, Invited speaker in a local meeting on GIST treatment in 2019: Bayer; Financial Interests, Personal, Invited Speaker, Invited speaker in a local meeting on immunotherapy: Amgen. All other authors have declared no conflicts of interest.