TRUST

To evaluate the antitumor activity of combined administration of standard doxorubicin and double immune modulation with Bintrafusp alfa in terms of 6-month progression-free rate (as per RECIST v1.1 criteria) after blinded centralized radiological review, in patients with advanced STS. Antitumor activity will be;PROT_TRUST_V3.0 du |19|04|2024| Page 9 sur 102;assessed independently for 2 distinct subgroups of patients, depending on the presence (TLS+) or absence (TLS-) of mature tertiary lymphoid structures.;Independently for each subgroup (TLS+ or TLS-):;À To evaluate the antitumor activity of combined administration of doxorubicin in association with Bintrafusp alfa in terms of 6-month objective response (as per RECIST v1.1 criteria), best overall response (as per RECIST v1.1 criteria), 1-year progression free survival (PFS) (as per RECIST v1.1 criteria) and 1- year overall survival (OS).;À To evaluate the antitumor activity of combined administration of doxorubicin in association with Bintrafusp alfa in terms of Immune response (iRECIST - Seymour et al 2017).;À To evaluate the safety of combined administration of doxorubicin in association with Bintrafusp alfa (NCI-CTC v5). The combination of Bintrafusp alfa with doxorubicin is not anticipated to have overlapping toxicity, pharmacodynamic or pharmacokinetic interaction, a formal phase I trial is therefore not required.;However, a safety run-in for tolerability will be implemented in the protocol to guarantee the absence of safety signals after the inclusion of the first 6, 12 and 18 patients (regardless of TLS status).;À Mandatory biomarker study: To perform pharmacodynamic/mechanism of action biomarkers analysis as well as predictive biomarkers analysis on pre-treatment and on-treatment tumor biopsies.