Microsatellite stable metastatic colorectal cancer (MSS-CRC) lacks mismatch repair deficiencies, has low mutational burden, and responds poorly to immunotherapy. It accounts for most CRC cases and is typically treated with chemotherapy and targeted therapies, often posing greater treatment challenges than MSI-H tumors. 

The Phase II study (NCT04440735) evaluates DSP107, a novel immune engager targeting CD47 and activating 4-1BB, in patients with third-line MSS colorectal cancerSearch disease. Patients received DSP107 alone or with atezolizumab. The trial aims to assess safety and early efficacy, especially in those with liver metastases.

Among efficacy-evaluable patients, the median overall survival had not yet been reached as of the May 2025 data cutoff but stood at 8.1 months for the DSP107 monotherapy group (n=19) and 17 months for the combination arm (n=21). Disease control was observed in 21% of patients receiving monotherapy and in 62% of those on combination treatment. 

Notable clinical responses included one patient achieving a complete response lasting over 2.5 years and another patient experiencing an 86% reduction in target lesions, with confirmed durable partial response and disappearance of both pulmonary and hepatic metastases lasting over 16 months. Immunofluorescence analysis of baseline liver metastasis biopsies showed uniformly high CD47 expression, consistent with DSP107’s tumor-targeting mechanism.

In the completed dose expansion Phase of the study, both DSP107 monotherapy and its combination with atezolizumab were well tolerated, with no dose-limiting toxicities reported. 

KOL insights

“This immunotherapy combination showed durable results in MSS-CRC patients. Not only is the median survival of DSP107 with atezolizumab longer than current standard treatments, but it is also very well tolerated by patients, without the severe, sometimes life-threatening side effects of chemotherapy in such advanced lines of treatment. Importantly, the majority of patients in the combination cohort had active liver metastases, and the activity and survival benefit were also seen in these patients, who are very difficult to treat, suggesting that DSP107 in combination with a PD1/PD-L1 checkpoint inhibitor may become an effective immunotherapy treatment option for this patient population”.– Expert Opinion

Conclusion

MSS occurs in 85% of all colorectal cancers (CRC). When compared to microsatellite instability-high (MSI-H) cancers, MSS-CRC shows resistance to immunotherapy strategies and  exhibits lower tumor mutational burden. Since more than 70% of patients with colorectal cancer who have metastasized have liver metastases that exhibit high levels of CD47 in response to first- and second-line chemotherapy regimens. Due to the lack of immune cell infiltration in tumors, prior attempts at immunotherapy for colorectal cancer have failed.

The Phase II dose expansion results of DSP107 in combination with atezolizumab demonstrate encouraging clinical activity and a favorable safety profile in heavily pretreated patients with third-line MSS-CRC—a population historically resistant to immunotherapy. The combination showed meaningful disease control and extended survival, including in patients with difficult-to-treat liver metastases. These results support the therapeutic potential of DSP107 as an immune-enhancing agent in MSS-CRC and provide a strong rationale for advancing to a randomized Phase IIb trial.

In addition to colorectal cancer, a Phase II expansion cohort for non-small cell lung cancer (NSCLC) with second- and third-line PD-1 experience is also evaluating DSP107, indicating the potential broad use of this innovative immunotherapy across a variety of solid tumor types. The company is expecting data in 2026 from a Phase II dose expansion cohort in NSCLC.