eClinicalMed: Efficacy of RNA oligonucleotide STNM01 in the second-line treatment of chemotherapy-refractory pancreatic cancer

The effect of stromal-targeted therapy on tumor immunosuppression has not been explored
.
STNM01, an RNA oligonucleotide, has been shown to inhibit the carbohydrate thiotransferase 15 (CHST15, involved in tumor proteoglycan synthesis and matrix remodeling).

This is an open-label, dose-escalation phase I/IIa study to evaluate the efficacy and safety
of STNM01 as a second-line in unresectable gemcitabine in combination with nab-paclitaxel refractory pancreatic ductal adenocarcinoma (PDAC).
A course of treatment consists of three 2-week endoscopic ultrasound-guided local injections of STNM01 and S-1 (80-120 mg twice daily, every 3 weeks for 14 days)
at doses of 250, 1000, 2500, or 10000 nM.
The primary endpoint was dose-limiting toxicity (DLT).

Secondary endpoints included overall survival (OS), tumor response rate, change in tumor microenvironment, and safety
.

Changes in tumor-infiltrating immune cells

A total of 22 patients were enrolled, with a maximum of 3 courses of treatment; No dose-limiting toxicity
was observed.
The median overall survival was 7.
8 months
.
The disease control rate was 77.
3%; In one patient, the visible lesions and tumor draining lymph nodes were completely absent
.
High expression of tumor CHST15 was associated with
poorer CD3+ and CD8+ T cell infiltration at baseline.
At the end of the first course of treatment, STNM01 significantly reduced CHST15 expression and increased tumor-invasive CD3+ and CD8+ T cell levels
in combination with S-1.
A doubling of CD3+ T cells is associated with
longer overall survival.
A total of 8 grade 3 adverse events
occurred.

Overall survival and progression-free survival of test patients

In conclusion, local injection of STNM01 as a combination second-line therapy is well
tolerated in patients with unresectable pancreatic ductal adenocarcinoma.
STNM01 may prolong patient survival by increasing the infiltration of T cells in the tumor microenvironment
.

Original source:

Toshio Fujisawa, et al.
STNM01, the RNA oligonucleotide targeting carbohydrate sulfotransferase 15, as second-line therapy for chemotherapy-refractory patients with unresectable pancreatic cancer: An open label, phase I/IIa trial.
eClinicalMedicine.
November 17, 2022.
https://doi.
org/10.
1016/j.
eclinm.
2022.
101731