KEY TAKEAWAYS
- The phase I and II trial assessed effectiveness of DSP107 with atezolizumab in patients with MSS-CRC.
- The primary endpoint was median PFS.
- The study revealed DSP107+PD(L)1 blockade showed promising anti-tumor activity and warrants further investigation.
DSP107 is a fusion protein combining SIRPα and the 4-1BB ligand (4-1BBL), tested for patients with colorectal cancer (CRC). Here, SIRPα targets CD47 on tumor cells to activate macrophages, anchoring trimeric 4-1BBL to the tumor to co-stimulate 4-1BB on immune cells. This results in tumor-localized activation of innate and adaptive immune responses. Phase 1 data showed excellent safety, with no red blood cell binding or dose-limiting toxicities (DLTs).
Anwaar Saeed and team aimed to evaluate safety and efficacy data from a phase 2 cohort of patients with microsatellite stable (MSS) CRC treated with DSP107 and atezolizumab.
Clinicians observed 27 patients with stage 3b/4 MSS-CRC who had progressed after two lines of therapy, including standard chemotherapy and targeted antibodies. They received weekly IV DSP107 infusions (10mg/kg) and atezolizumab (1200 mg) every 3 weeks. Most patients (67%) had liver metastases and BRAF/KRAS mutations. Restaging imaging was done every two months using RECIST v1.1 criteria.
The results showed that DSP107 combined with atezolizumab was well tolerated with no DLTs. The most common treatment-related adverse events were infusion-related reactions (IRR; 44.4%), fatigue (18.5%), and grade 1 anemia and eosinophilia (11.1% each). IRRs were managed by slowing the infusion rate and giving IV fluids.
Among 21 evaluable patients, the median PFS was 20 weeks. Disease control was achieved in 62% of patients (13/21), with two patients showing significant (≥80% target lesion reduction) and lasting (>15 months) responses, including the disappearance of lung and liver metastases.
The study concluded that DSP107 combined with PD(L)1 blockade shows promising anti-tumor activity in MSS CRC, even in patients with liver metastases, and should be further investigated.
The trial was sponsored by Kahr Medical.
Source: https://cslide.ctimeetingtech.com/esmogi24hybrid/attendee/confcal/show/session/3
Clinical Trials: https://www.clinicaltrials.gov/study/NCT04440735
Saeed A, Zhang J, Bashir B et al. (2024). “Phase II dose expansion study of DSP107, a first-in-class fusion protein targeting CD47 and 4-1BB, in combination with atezolizumab in patients with advanced MSS colorectal cancer.” Presented at ESMO GI 2024. (Abstract 51P)
