Ignite Creation Date:
2024-05-06 @ 9:24 AM
Last Modification Date:
2024-10-26 @ 12:14 PM
Study NCT ID:
NCT02977195
Status:
COMPLETED
Last Update Posted:
2022-07-25
First Post:
2016-11-25
Brief Title:
First in Human Evaluation of Safety Pharmacokinetics and Clinical Activity of a Monoclonal Antibody Targeting Netrin 1 in Patients With AdvancedMetastatic Solid Tumors
Sponsor:
Centre Leon Berard
Organization:
Centre Leon Berard
Study Overview
Official Title:
NP137 - An Open-label First in Human Phase I Trial Aiming to Evaluate the Safety Pharmacokinetics and Clinical Activity of a Humanized Monoclonal Antibody Targeting Netrin 1 NP137 in Patients With AdvancedMetastatic Solid Tumors
Status:
COMPLETED
Status Verified Date:
2022-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
NP137
Brief Summary:
For most advanced solid tumors current therapy is inadequate at improving quality of life slowing progression of disease prolonging survival and providing a cure Hence there is a continuous need for innovative safer and more effective anti-cancer therapies Our study is based on the dependence receptor paradigm and the associated therapeutic strategy In preclinical models preventing Netrin-1 interaction with its receptors is sufficient to trigger Netrin-1-expressing tumor cell death in vitro as well as tumor growth and metastasis inhibition in vivo This indicates that a therapeutic approach based on Netrin-1Netrin-1 receptors interaction inhibition is both feasible and promising NP137 is a first-in-class humanized monoclonal antibody targeting the Netrin-1 ligand a secreted protein recently described as a driver of tumor initiation and progression NP137 demonstrated anti-tumor activity as a single agent in several pre-clinical models of cancer including breast and lung cancer Taken together several studies strongly support the rational for preclinical development and clinical evaluation of a highly potent and selective anti-Netrin-1 antibody in cancer patients The proposed study is an open label multicenter Phase I dose escalation study to assess the safety tolerability pharmacokinetic PK pharmacodynamic PD and preliminary anti-tumor activity of NP137 administered every 2 weeks Q2W as single agent in patients with locally advanced or metastatic solid tumors This trial will be the First in Human FIH study for NP137 there is no clinical experience with this antibody in the clinic The study consists of 3 parts
Part 1 a dose escalation part to define the Maximum tolerated dose and the Recommended Phase II dose MTD RP2D of NP137 as well as to research some PD biomarkers Biological collection cohorts - This part is now completed with Last Patient In on December 20th 2018 - Part 2 an expansion part1 to investigate NP137 clinical activity as a single agent by collecting the 3-month objective response rate ORR3m
Part 3 an expansion part2 to investigate NP137 clinical activity as a single agent by collecting the 3-month objective response rate ORR3m in RH patients with endometrial carcinoma
Part 1 a dose escalation part to define the Maximum tolerated dose and the Recommended Phase II dose MTD RP2D of NP137 as well as to research some PD biomarkers Biological collection cohorts - This part is now completed with Last Patient In on December 20th 2018 - Part 2 an expansion part1 to investigate NP137 clinical activity as a single agent by collecting the 3-month objective response rate ORR3m
Part 3 an expansion part2 to investigate NP137 clinical activity as a single agent by collecting the 3-month objective response rate ORR3m in RH patients with endometrial carcinoma
Detailed 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 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 33 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 mgkg
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
In expansion parts patients are treated at the RP2D defined in Part 1 14 mgkg
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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2015-003907-41 | EUDRACT_NUMBER | None | None |