Anti-tumor activity of LNA-i-miR-221
LNA-i-miR-221, tumor, Tumor, toxicity, SD, PD, colon carcinoma
DISEASE PROGRESSION, TUMOR, REGRESSION, LIVER METASTASES, TUMOR, INTESTINAL ADENOCARCINOMA, DISEASE, MAY, COLON CARCINOMA
Finally, exploratory analysis of the putative anti-tumor activity of LNA-i-miR-221 was also planned. The effect of administration of LNA-i-miR-221 on tumor size in each patient was determined by analysis of CT scan images, which were assessed in accordance with the RECIST 1.1 criteria. This analysis showed that eight patients had stable disease (SD) (50.0%) during the study, while seven patients (43.8%) had progressive disease (PD) (Table RECIST 1.1. responses in patients evaluable for clinical activityPercentages are based on the number of subjects within each cohortCR = Complete response, PR = Partial response, SD = Stable disease, PD = Progressive diseaseExcept for the patient who received a 5 mg/kg dose and displayed a partial response (PR), there were no major differences in terms of tumor response among the cohorts. Figure Tumor responses and patient outcomes during the course of this study: The patient assessed with a PR was subsequently treated with three additional cycles of LNA-i-miR-221, on a compassionate use basis, at the same dose (5 mg/kg) as used in the escalation cohort. CT scan images showing tumor shrinkage over time in this patient are presented in Fig. Progressive tumor shrinkage in a 60-year-old metastatic colon carcinoma patient with confirmed PR evaluated on three index lesions. The patient underwent left hemicolectomy in 2018 with histological evidence of moderately differentiated intestinal adenocarcinoma, RAS mutated. The patient was treated for stage IV disease with multiple regimens (FOLFOX plus Bevacizumab followed by surgical resection of liver metastases; FOLFIRI plus Aflibercept, FOLFOX, FOLFIRI rechallenges, Trifluridine/Tipiracil, and Regorafenib). The patient had disease progression and was enrolled within cohort V (5 mg/kg for four consecutive days). The RECIST 1.1 assessment after the first cycle with LNA-i-miR-221 showed a clinical benefit. The patient received three subsequent treatment cycles on a compassionate use basis (pre-planned in the study protocol for patients with clinical response). The CT-image shown in the Figure demonstrates disease regression at cycle 1 with deepening response after cycle 4. Further tumor regression of the residual liver lesion has been observed after 7 months of follow-up. At the present (May 2023) the patient is still alive with PS 0We conclude that the MTD was not reached in this study and we set the RP2D at 5 mg/kg, considering the absence of major toxicity, the favourable PK profile, the more pronounced PD activity, and the occurrence of anti-tumor activity, as demonstrated by a persisting, and increasing major response.