First in Human Evaluation of Safety, Pharmacokinetics, and Clinical Activity of a Monoclonal Antibody Targeting Netrin 1 in Patients With Advanced/Metastatic Solid Tumors

Summary

Participation Requirements

Description

The dose escalation part (NP137 administered as a single agent by intravenous injection with 7 ascending dose levels) has been initiated with an accelerated dose titration with 1 patient per DL until the occurrence of a ? Grade 2 drug-related AE. Following the occurrence of such moderate toxicity, p...

The dose escalation part (NP137 administered as a single agent by intravenous injection with 7 ascending dose levels) has been initiated with an accelerated dose titration with 1 patient per DL until the occurrence of a ? Grade 2 drug-related AE. Following the occurrence of such moderate toxicity, patients have been enrolled in a slower dose escalation design with at least 3 patients per DL using a Modified Continual Reassessment Method. Of note, in case no toxicity occurs up to the DL4, the classical 3+3 design has been initiated. Cohorts of patients with biopsable disease have been added in order to assess the impact of NP137 treatment on epithelial phenotype signature (assessed by RNAseq and subsequent bioinformatic profiling using published E vs M score). Up to 4 additional and independent cohorts of patients (n= up to 6 pts/ cohort) with biopsable disease have been enrolled. Starting from DL4, the enrolment in such cohort will be allowed at highest DL that has cleared its DLT assessment window. Such cohorts will allow to collect pre and on-treatment tumor biopsies in order to identify PD biomarkers correlated to NP137 clinical activity. In expansion parts, patients are treated at the RP2D defined in Part 1 (14 mg/kg). In both parts, NP137 will continue to be administered as long as patient experience clinical benefit in the opinion of the investigator or until unacceptable toxicity or symptomatic deterioration attributed to disease progression as determined by the investigator after an integrated assessment of radiographic data and clinical status or withdrawal of consent or patient willingness to stop the treatment.

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