DSP107 (CD47×4-1BB) + atezolizumab doubles survival and controls disease in 62% of refractory MSS colorectal cancers

DSP107 is a bi-specific fusion protein that tethers trimeric 4-1BBL to CD47 overexpressed on tumour cells, delivering conditional activation of immune response.. In a phase 2 expansion (NCT04440735), 50 heavily pre-treated metastatic MSS CRC patients (⩾2 prior lines) were randomised to weekly DSP107 (n = 19) or combined with atezolizumab (n = 21). Liver metastases were present in 76%. Treatment was well-tolerated; grade 3 IRRs or fatigue occurred in 4%. **Median overall survival has not yet been reached but reached at least 7.6 mo with DSP107 monotherapy and 14.6 mo with the atezolizumab combo.**Disease control (CR + PR + SD) was attained in 26% and 62% of evaluable patients, respectively, including one durable CR (> 2.5 y) and a confirmed 86% tumour reduction PR lasting > 16 mo. No dose-limiting haematologic or hepatic toxicities were seen. For comparison, third-line standards regorafenib or trifluridine/tipiraciltypically yield 0–4% objective responses, ~3 mo PFS and 5–8 mo OS.