Neoplasms

Digestive System Diseases

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Antineoplastic Agents

All Drugs and Chemicals

Folfirinox

Patient receive two doses of the study drug, NP137, approximately two weeks apart. This will be followed by surgery. After the surgery if feasible, patients will begin post-surgical treatment with a standard-of-care chemotherapy regimen called FOLFIRINOX, combined with the study drug, NP137, for a total duration of about 6 months. Upon completing this phase, patients will receive an additional 6 months of treatment with only the study drug NP137.

NP137 for the Treatment of Resectable Pancreatic Cancer

NP137

Nabeel Badri

The objective of this study is to investigate whether adding the study drug, NP137, to a patient's treatment regimen (before surgery and in combination with chemotherapy afterward) can alter the behavior of pancreatic cancer..

The aim of this study is to evaluate the mechanism of action for a novel anti-Netrin-1 antibody (NP137) in patients with pancreatic ductal adenocarcinoma. Pre-clinical data indicates that anti-Netrin-1 therapy can prevent/delay metastatic progression of disease by inducing cancer cell death through its dependence receptor Unc5b as well as prevent epithelial to mesenchymal transition (EMT).

This pilot study is designed to provide vital translational scientific information that will inform the design of future clinical trials for NP137. This information includes determining the optimal use of NP137 with cytotoxic, as well as the treatment setting of resectable pancreatic cancer.

Study of Perioperative NP137 and FOLFIRINOX in Resectable Pancreatic Cancer

A Pilot Study of Perioperative NP137 and FOLFIRINOX in Resectable Pancreatic Cancer

EMT score is determined by the mean expression of mesenchymal genes minus the mean expression of epithelial genes Therefore, a positive EMT score suggests a mesenchymal status (worse outcome), whereas a negative score indicates an epithelial status (better outcome).

Pathologic response rate after treatment with NP137. The Pathological Response definition will follow the College of American Pathologists criteria

Metastasis-free survival at two years. Metastasis-free survival is defined as the time between the date of enrollment and the date of the 1st distant event occurrence .

Disease free survival defined as time from the date of enrollment until the date of the first cancer-related event, second cancer, or death from any cause.

Overall survival is defined by the date of enrollment to date of death from any cause

Descriptive of Adverse event during the trial.

NETRIS Pharma

Assistant Professor

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Micronutrients

Bone Density Conservation Agents

Hematinics

Vitamins

Oxaliplatin

Leucovorin

Fluorouracil

Irinotecan

Levoleucovorin

Calcium

Calcium, Dietary

Hormones

Topoisomerase I Inhibitors

Enzyme Inhibitors

Antidotes

Protective Agents

Folic Acid

Vitamin B Complex

Trace Elements

Folinic Acid

Folate

Vitamin B9

NP137 will be administrated at the first day of each cycle (CnD1) of 14 days as an IV infusion at 9 or 14 mg/kg.

Oxaliplatin will be administreted at the first day of each cycle (CnD1) of 14 days as an IV infusion at 85 mg/m²

Irinotecan will be administreted at the first day of each cycle (CnD1) of 14 days as an IV infusion at 150 mg/m²

Calcium levofolinate will be administreted at the first day of each cycle (CnD1) of 14 days as an IV infusion at 100 mg/m²

Calcium levofolinate

5 FU will be administreted at the first day of each cycle (CnD1) of 14 days as an IV infusion at 2400 mg/m2 as a continuous intravenous infusion over 46 hours.

5 FU

Anna BOROWIK

Laure Bordy

Gaël ROTH

Jean Fredéric BLANC

Anthony TURPIN

Pascal ARTRU

Jean-Baptiste BACHET

Camille EVRARD

Olivier BOUCHE

Astrid LIEVRE

Nicolas WILLIET

Gaël ROTH, MD PHD

The study will assess the safety of the association of NP137 with the standard of care mFOLFIRINOX in the treatment of locally advanced pancreatic ductal adenocarcinoma.The study drug which is tested is the NP137 in association with mFOLFIRINOX to allow a better tumor response as well as better survival outcomes with an acceptable safety.

The study is a multicentric, prospective, single arm phase 1b trial. This study will enroll 43 to 52 patients and consists of 2 parts: Safety Lead-in Phase and Expansion Phase. Initially, 3 to 12 patients will be enrolled into a Safety Lead-in Phase based on a 3 + 3 design, with the possibility of dose de-escalation, to confirm the recommended dose of NP137.The Expansion Phase will start after completion of Safety Lead-in Phase at the confirmed dose and will include 40 patients. Patients will be assigned to the experimental arm (NP137 + mFOLFIRINOX).

Multicentric prospective single arm phase 1b trial.

Study Investigating the Association of NP137 With mFOLFIRINOX in Locally Advanced Pancreatic Ductal Adenocarcinoma

Percentage Proportion of patients experiencing adverse events (AEs) of any grade and grade 3/4 AEs as defined by the National Cancer Institute - Common Terminology Criteria for Adverse Events (CTCAE v 5.0) at 6 months.

Best overall objective response rate (ORR) according to RECIST 1.1

Median Overall survival (OS) and 12 months-OS rates. OS is defined as the time between inclusion and death (all causes). Patients alive will be censored at the date of last news.

Median Progression-Free Survival (PFS) and 12 months-PFS rates. PFS is defined as the time between inclusion and progression according to RECIST 1.1 or death (all causes). Patients alive without progression will be censored at the date of last news.

Median Duration of response is defined as the time between first dose of treatment and progression according to RECIST 1.1. Patients alive without progression will be censored at the date of last news.

Quality of life will be studied by using the EORTC QLQ-C30 questionnaire (European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire for Cancer). A 5-point decrease of QLQ-C30 score will be considered as the minimal clinically significant deterioration of QoL.

TTD will be defined as the time from inclusion in the study to deterioration of EORTC QLQ-C30 score with a decrease ≥5 points at any time point after the baseline score.

PK-PD evaluation: based on available PopPK modelisation and PK samples collected at the time of the response evaluation in this study

Percentage surgical resection with R0/R1 margins

University Hospital, Grenoble

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Endometrial Neoplasms

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Antibodies

Antibodies, Monoclonal

Paclitaxel

Carboplatin

Pembrolizumab

Albumin-Bound Paclitaxel

Immunomodulating Agents

Immunoglobulins

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Standard Chemotherapy will be adminitred in 2 independant cohorts: Endometrial carcinoma or Cervix Carcinoma

Experimental double combination \[Standard Chemotherapy +NP137\] will be administred in 2 independant cohorts: Endometrial carcinoma or Cervix Carcinoma

Experimental double combination \[Pembrolizumab +NP137\] will be administred in 2 independant cohorts: Endometrial carcinoma or Cervix Carcinoma

Experimental triple combination \[Pembrolizumab+ Standard Chemotherapy + NP137\] will be administred in 2 independant cohorts: Endometrial carcinoma or Cervix Carcinoma

Recombinant humanized IgG1 monoclonal antibody against Netrin 1. NP137 will be administred IV, Q3W until disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, pregnancy or SMPC guidance, whichever occurs first.

Humanised monoclonal anti-programmed cell death-1 (PD-1) antibody will be administred in IV Q3W. A maximum 35 cycles of treatments (approximately 2 years) with pembrolizumab can be administered to patients.

Standard Chemotherapy agent will be administred IV, Q3W, up to 6 cycles of treatment.

Ray-Coquard Isabelle, MD, PhD

Elsa KALBACHER, MD

Coriolan LEBRETON, MD

Florence JOLY, MD

Jean-David FUMET, MD

Cyril ABDEDDAIM, MD

Isabelle RAY COQUARD, MD,PhD

Magali PROVANSAL, MD

Michel FABBRO, MD

Jean-Sébastien FRENEL, MD

Frederic SELLE, MD

Alexandre DE MOURA, MD

Alexandra LEARY, MD

Jerome ALEXANDRE, MD, PhD

Thibault DE LA MOTTE ROUGE, MD

Laurence GLADIEFF, MD

The aim of this study is to investigate the safety and the clinical activities of NP137 when combined with pembrolizumab and/or chemotherapies in patients with advanced/metastatic gynecological cancers (2 types: endometrial carcinoma and cervix carcinoma).

The prognosis of patients with locally advanced/metastatic uterine (endometrial or cervical) cancer progressing/relapsing after at least one prior systemic treatment remains poor. The development of new innovative anti-tumor drug candidates as single agent or in combination with chemotherapy or check point inhibitors is needed.

NP137 is a first-in-class humanized monoclonal antibody targeting specifically and selectively Netrin-1. By blocking Netrin-1, NP137 is capable of restoring apoptosis in tumor cells in vitro and in vivo, leading to therapeutic activity in various animal cancer models.

Dependence receptors inhibitor such as NP137 might be a novel choice to improve the clinical outcomes of these patients.

The herein proposed study will be a multicenter, open-label, randomized, Phase I/II trial with:

A safety run in part to assess the safety of the therapeutic combinations for the first 6 patients enrolled in each of the therapeutic combinations independently of the tumor type. According to safety rules, these therapeutic combinations will be investigated or not in the Phase II part.

A Phase II part will be then conducted using an adaptive Bayesian approach allowing to quickly stop treatment cohorts without evidence of efficacy and/or select promising treatment cohorts. The Phase II part will be initiated with a preliminary step to assess the clinical activity of the proposed therapeutic combinations in 2 tumor types before proceeding to the activation of extension phase II part of the study. For each cohorts, clinical activity will be assessed through by sequential statistical analysis at specific timepoints.

GYNecological Cancers Treated With NETrin mAbs in Combination With Chemotherapy and /or Pembrolizumab

A Randomized, Multicenter, Open Label, Phase I/II Study to Evaluate the Safety, Clinical and Biological Activity of a Humanized Monoclonal Antibody Targeting Netrin-1 (NP137) in Combination With Carboplatin Plus Paclitaxel and/or Pembrolizumab in Patients With Locally Advanced/Metastatic Endometrial Carcinoma or Cervix Carcinoma Progressing/Relapsing After at Least One Prior Systemic Chemotherapy.

Any pre-definied toxicities graded by using NCI CTCAE Version 5.0 and assessed by the investigator to be possibly, probably, or definitely related to study treatments administration during the safety run in period

Rate of patients with CR or PR as per RECIST 1.1

The proportion of evaluable patients with an objective response according to RECIST 1.1.

Time interval from the date of first occurrence of a documented objective response (CR or PR, whichever status is recorded first) until the first date that disease progression or death is documented,

Time from first study drug intake until disease progression or death, whichever occurs first

Time from the first day of study treatment to the date of death due to any cause.

The best response designation between the date of the first study treatment and the date of objectively documented progression or the date of subsequent anti-cancer therapy

Area under the concentration-time curve from time zero to the last sample with the quantifiable concentration

Area under the concentration-time curve from time zero to infinity corresponding to the definite integral of a curve that describes the variation of a drug concentration in blood plasma as a function of time (drug exposure in plasma)

Clearance: volume of plasma from which NP137 is completely removed per unit time.

Terminal elimination half-life: time required for the amount of NP137 in the body to decrease by half.

Merck Sharp & Dohme LLC

Centre Leon Berard

Blood and Lymph Conditions

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Venetoclax

Azacitidine

Antimetabolites

Patients who meet primary refractory disease definition according to ELN criteria after 2 cycles of standard \[AZACITIDINE +VENETOCLAX\] (i.e: patients who have failed to have a complete remission (with complete (CR) or incomplete hematologic recovery (CRi))

IV infusion, 14mg/kg or 9mg/kg, every 2 weeks

Subcutaneous injection, 75 mg/m², on cycle Days 1-7 (28-days cycle)

Azacitidine Injection

Anne-Sophie MICHALET, MD

The aim of this study is to investigate the safety and the clinical activities of NP137 when combined with Azacitidine and Venetoclax in patients with refractory acute myeloid leukemia after 2 cycles of Azacitidine and Venetoclax.

The dual treatment, VENETOCLAX and AZACITIDINE, is the standard of care for patients with newly diagnosed AML who are ineligible for intensive chemotherapy. However, upfront resistance as well as relapse following initial response demonstrate the need to improve this therapeutic strategy.

NP137 is a first-in-class humanized monoclonal antibody targeting specifically and selectively Netrin-1. Based on data collected from non clinical studies NP137 should act in synergy with VENETOCLAX and AZACITIDINE to reactivate and enhance the apoptotic pathway in AML cells.

The herein proposed study to assess the safety (Safety run in/ phase I part) and the preliminary efficacy signal (extension phase II part) of the NP137 when combined to AZACITIDINE AND VENETOCLAX in patients with refractory acute myeloid leukemia after 2 cycles of Azacitidine and Venetoclax.

This study will be an open-label, Phase I/II trial. the first part, consists to a safety run to assess the security and the tolerability of the drugs combination from the first 6 to 12 first patients enrolled into the study. All patients will receive a fixed dose of NP137 at the RP2D (Recommended Phase 2 Dose) determined from the First in human NP137 study(DL1) . A dose deescalation of NP137 is planned to DL-1 according to the Dose Limiting Toxicities observed during this period. The second part will be will be then conducted as a phase II using an adaptive Bayesian approach allowing to quickly stop treatment without evidence of efficacy. The clinical activity will be assessed based on ELN (European LeukemiaNet) criteria 2027 for the Acute Myeloid Leukemia.

The therapeutic combinations NP137 + \[AZACITIDINE+VENETOCLAX\] will be administered on the first 6 patients enrolled in the study at Dose Level (14 mg/kg). According to safety rules based on the dose limiting toxicities occurence, a dose reduction of NP137 at Dose Level -1 (9 mg/kg) will be assessed in 6 additional patients.

After the safety run in part, study will be opened with 35 patients (including patients from the safety run in) at DL or DL-1.

Acute Myeloid Leukemia Treated With With NETrin Abs in Combination With [AZACITIDINE + VENETOCLAX]

A Phase I/II Study to Evaluate the Safety Clinical and Biological Activity of a Humanized Monoclonal Antibody Targeting Netrin-1 (NP137) in Combination With Standard AZACITIDINE+ VENETOCLAX in Patients With Refractory Acute Myeloid Leukemia

To assess the safety of the proposed therapeutic combination \[NP137 + AZACITIDINE VENETOCLAX\] according to the incidence of Dose Limiting Toxicities (DLT) as defined per protocol.

To investigate the clinical activity of the proposed therapeutic combination \[NP137 + AZACITIDINE + VENETOCLAX\] through the Objective Response Rate (ORR) over the 4 cycles of AZACITIDNE +VENETOCLAX+ NP137 administration.

ORR will be defined as the proportion of patients with a complete remission (CR) or complete remission with incomplete hematologic recovery (CRi), as best overall response over the 4 cycles of the study combination.

Incidence of any adverse events graded according to NCI-CTCAE V5.0

Measurement of the duration of response (CR/CRi)

Best overall response, is determined by the best response designation. For subjects without documented progression or subsequent anticancer therapy, all available response designations will contribute to the BOR determination :from the date of first intake of study drug until progression or at time of initiation of a new anti-cancer treatment

Objective Response Rate after 2 cycles of study treatment defined as the proportion of participants who achieve: complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) after 2 cycles of treatment (2 cycles of A+V including 4 injections of NP137)

Overall survival measured from the date of treatment start to the date of death from any cause; patients not known to have died at last follow-up are censored on the date they were last known to be alive.

Progression Free survival defined as the time from the initiation of the study treatment until first evidence of disease treatment failure : from the date of first intake of study drug until progression

Time to Treatment Failure Rate (TTF) defined as the time from the initiation of study treatment to its early discontinuation. Reasons for prematurely discontinuing treatment can include cancer progression but also adverse events, patient choice, or death.

Death in Medullary Aplasia Rate based on cytological assessment: Deaths occurring ≥7 days following completion of initial treatment while cytopenic, with an aplastic or hypoplastic bone marrow obtained within 7 days of death, without evidence of persistent leukemia.

Time to neutrophil / platelet count recovery (absolute neutrophil count (ANC) \> 1 × 109/L (defined as neutrophil recovery) and platelet count \> 100 × 109/L (defined as platelet recovery)).

Carcinoma, Hepatocellular

Liver Neoplasms

Liver Diseases

Bevacizumab

Atezolizumab

Angiogenesis Inhibitors

Growth Inhibitors

NP137 at 9 or 14 mg/kg IV will be administered every 21 days.

Atezolizumab will be administered by IV infusion at a fixed dose of 1200 mg on Day 1 of each 21-days cycle

Bevacizumab will be administered by IV infusion at a dose of 15 mg/kg on Day 1 of each 21-day cycle

ROTH, Gaël

The study will assess the safety of the association of NP137 with the standard of care Atezolizumab-Bevacizumab in first line setting in patients with unresectable hepatocellular carcinoma.The study drug which is tested is the NP137 in association with Atezolizumab-Bevacizumab to allow a better tumor response as well as better survival outcomes with an acceptable safety.

The study is a multicentric, prospective, single arm phase 1b trial. This study will enroll 43 to 52 patients and consists of 2 parts: Safety Lead-in Phase and Expansion Phase. Initially, 3 to 12 patients will be enrolled into a Safety Lead-in Phase based on a 3 + 3 design, with the possibility of dose de-escalation, to confirm the recommended dose of NP137 .The Expansion Phase will start after completion of Safety Lead-in Phase at the confirmed dose and will include 40 patients. Patients will be assigned to the experimental single arm (NP137+ Atezolizumab-Bevacizumab).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Perioperative NP137 and FOLFIRINOX in Resectable Pancreatic Cancer	NCT06203821	Pancreatic Canc...	NP137	18 Years -	University of Rochester
Study Investigating the Association of NP137 With mFOLFIRINOX in Locally Advanced Pancreatic Ductal Adenocarcinoma	NCT05546853	Pancreatic Duct...	NP137 Oxaliplatin Irinotecan Calcium levofol... 5 FU	18 Years -	University Hospital, Grenoble
GYNecological Cancers Treated With NETrin mAbs in Combination With Chemotherapy and /or Pembrolizumab	NCT04652076	Endometrial Car... Cervix Carcinom...	NP137 Pembrolizumab Paclitaxel Carboplatin	18 Years -	NETRIS Pharma
Acute Myeloid Leukemia Treated With With NETrin Abs in Combination With [AZACITIDINE + VENETOCLAX]	NCT06150040	Acute Myeloid L...	NP137 Azacitidine Inj... Venetoclax	65 Years -	Centre Leon Berard
Acute Myeloid Leukemia Treated With With NETrin Abs in Combination With [AZACITIDINE + VENETOCLAX]	NCT06150040	Acute Myeloid L...	NP137 Azacitidine Inj... Venetoclax	65 Years -	Centre Leon Berard
Acute Myeloid Leukemia Treated With With NETrin Abs in Combination With [AZACITIDINE + VENETOCLAX]	NCT06150040	Acute Myeloid L...	NP137 Azacitidine Inj... Venetoclax	65 Years -	Centre Leon Berard
Study Investigating the Association of NP137 With Atezolizumab-Bevacizumab Combination in First Line in Unresectable HCC	NCT05546879	Hepatocellular ...	NP137 Atezolizumab Bevacizumab	18 Years -	University Hospital, Grenoble

Spots Global Cancer Trial Database for np137

Every month we try and update this database with for np137 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for np137

Every month we try and update this database with for np137 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for np137 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.