P-126 TROPION-PanTumor03, a phase 2, multicentre study of datopotamab deruxtecan (Dato-DXd) as monotherapy and in combination with anticancer agents in patients with advanced/metastatic solid tumours: Substudies in gastric and colorectal cancer

Patients with advanced/metastatic gastric cancer (GC) or colorectal (CRC) have poor prognosis, so there is an unmet need for new therapeutic agents in these settings. Trophoblast cell surface protein 2 (TROP2) a transmembrane glycoprotein overexpressed many epithelial cancers, including GC and CRC. Dato-DXd antibody-drug conjugate consisting of humanised anti-TROP2 IgG1 monoclonal antibody covalently linked to highly potent topoisomerase I inhibitor payload via stable, tumour-selective, tetrapeptide based cleavable linker. monotherapy has demonstrated encouraging preliminary activity safety lung breast cancers (TROPION-PanTumor01; NCT3401385). TROPION-PanTumor03 (NCT05489211) phase 2, multicentre, open-label trial comprising five independent substudies evaluating as and/or combination various anticancer across several tumour types. Here we describe Substudies 5 (CRC). In all substudies, eligible patients are aged ≥18 years histologically/cytologically documented advanced metastatic disease, ECOG PS 0/1, ≥1 measurable target lesion (RECIST 1.1) not previously irradiated, adequate bone marrow organ function, available FFPE sample. Substudy must HER2-negative, unresectable gastric/gastroesophageal junction oesophageal carcinoma confirmed predominant adenocarcinoma histology. 5, TROP2+, microsatellite stable the colon rectum. comprises three therapy cohorts (each n≈40). programmed death-ligand 1 combined positive score (PD-L1 CPS) orally BID on days 1–14; 5-fluorouracil, 800 mg/ m2 IV 1–5, q3w; nivolumab, 360 mg q3w. one (n≈80; Cohort 5A) cohort (n≈40; 5B). 5A, will receive 3L+ monotherapy. 5B, 1L + 5-fluorouracil leucovorin bevacizumab OR capecitabine bevacizumab. 5B be ungated by data from 5A. Dosing: 4 6 mg/kg q3w (based dose finding Cohorts 2A/2B); 400 day 1200 1–2, q2w; leucovorin, 1, capecitabine, 1000 1–14, bevacizumab, q2w (in leucovorin) 7.5 capecitabine). treatment until disease progression, unacceptable toxicity, withdrawal. Primary endpoints objective response rate safety. Key secondary include progression-free survival, overall survival duration response, while exploratory biomarker analysis TROP2 expression. Recruitment ongoing March 2023. NCT05489211. Medical writing support development this abstract, under direction authors, was provided Eric Exner Ashfield MedComms (Milwaukee, WI, USA), Inizio company, funded AstraZeneca.