Nerofe administered intravenously 3x/week

Nerofe

Yoram Devary, PhD

This study will be the first to test the anti-cancer peptide Nerofe in humans. It will evaluate the safety, pharmacokinetic behavior, and pharmacodynamic and clinical effects of Nerofe given intravenously every other day to patients with advanced malignant disease.

This is a Phase 1 single-center, open-label, non-randomized, dose-escalation study, to be conducted in 2 phases. The Dose Escalation Phase will determine the maximum tolerated dose (MTD) of Nerofe and evaluate its safety and tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary clinical effects. The subsequent Dose Confirmation Phase will be a cohort expansion at or below the MTD of Nerofe. Subjects will be treated with IV doses of Nerofe thrice weekly (on alternating days) in consecutive, 28-day cycles. Subjects will be evaluated regularly for safety. Subjects who tolerate the drug and who do not experience progressive disease, intolerable toxicity, or meet any of the other withdrawal criteria may continue to receive Nerofe for up to 6 cycles, at the discretion of the Principal Investigator. Throughout the trial, oversight will be provided by the Clinical Safety Committee.

Phase 1 Trial of Intravenously Administered Nerofe™ in Subjects With Advanced Malignancies

A Phase 1, Open-Label, Dose-Escalation Study Evaluating the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Effects of Intravenously Administered Nerofe™ in Subjects With Advanced Malignancies

Immune System Key Ltd

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Doxorubicin

Liposomal doxorubicin

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

weekly doses of NEROFE at 96 mg/m2, intravenously over 60 minutes

weekly doses of NEROFE at 48 mg/m2, intravenously over 60 minutes

weekly doses of NEROFE at 192 mg/m2, intravenously over 60 minutes

weekly doses of NEROFE at 288 mg/m2, intravenously over 60 minutes

weekly doses of NEROFE (48-288 mg/m2) (dose level 1: 96 mg/m2, dose level -1: 48 mg/m2, dose level 2: 192 mg/m2, dose level 3: 288 mg/m2), intravenously over 60 minutes

NEROFE

weekly doses of 8 mg/m2 (fixed dose), intravenous push over 3 mins;

Jennifer Montcalm

Benjamin Weinberg, MD

The goal of this clinical trial is to learn about the safety of NEROFE and doxorubicin and how well it works in patients with advanced/unresectable or metastatic solid KRAS-mutated and ST-positive solid tumors. The main question it aims to answer is to find the recommended dose and scheduled for the combination of NEROFE and doxorubicin. Participants will receive weekly doses of NEROFE and doxorubicin.

NEROFE and Doxorubicin in KRAS-mutated ST2-positive Solid Tumors

Phase I Study of NEROFE and Doxorubicin in KRAS-mutated ST2-positive Solid Tumors

Safety and tolerability of NEROFE and doxorubicin in patients with advanced KRAS-mutated and ST2-positive solid tumors

Pharmacokinetics of NEROFE and doxorubicin in patients with advanced KRAS-mutated and ST2-positive solid tumors; AUC 0-24 hours calculated using the trapezoidal rule \[(Concentration at 0 hour + concentration at 24 hours) x 24\]/2

Pharmacokinetics of NEROFE and doxorubicin in patients with advanced KRAS-mutated and ST2-positive solid tumors; maximum 24 hour concentration

Pharmacokinetics of NEROFE and doxorubicin in patients with advanced KRAS-mutated and ST2-positive solid tumors; minimum 24 hours concentration

Pharmacokinetics of NEROFE and doxorubicin in patients with advanced KRAS-mutated and ST2-positive solid tumors; hour at which Cmax occurs

Pharmacokinetics of NEROFE and doxorubicin in patients with advanced KRAS-mutated and ST2-positive solid tumors; the time at which the concentration is at half its initial value

Pharmacodynamics of NEROFE and doxorubicin in patients with advanced KRAS--mutated and ST2-positive solid tumors; Change in ST2 expression by IHC will be quantified by percentage of positively stained cells in pre- vs. on-treatment tumor biopsies

Pharmacodynamics of NEROFE and doxorubicin in patients with advanced KRAS-mutated and ST2-positive solid tumors; Change in KRAS mRNA will be quantified by qPCR in blood and tissue (pre- vs. on-treatment blood samples and tumor biopsies).

time from the date of the initial treatment to the date of first documented disease progression or death due to any cause, whichever occurs first.

Overall Survival (OS): defined as the date of the initial treatment to the date of the participant's death.

The proportion of participants who achieve a PR or better according to the RECIST version 1.1 criteria.

Georgetown University

Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Rare Diseases

Syndrome

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Myelodysplastic Syndromes

Neoplasms by Histologic Type

Hematologic Diseases

Bone Marrow Diseases

Precancerous Conditions

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Hormones

Daunorubicin

48mg/m2 IV Nerofe + Doxorubicin 10mg/m2 - once a week

96mg/m2 IV Nerofe + Doxorubicin 10mg/m2 - once a week

Nerofe is a first-in-class hormone-peptide with cancer suppressive properties. Nerofe is a derivative of the human hormone-peptide Tumor-Cells Apoptosis Factor (TCApF). It contains 14 amino-acids. Binding Nerofe to the T1/ST2 receptor caused a rapid activation both of Caspase 8 and Bcl-2 mediated downstream in proliferating cancer cells.

Doxorubicin is an anthracycline antibiotic with antineoplastic activity. Doxorubicin, isolated from the bacterium Streptomyces peucetius var. caesius, is the hydroxylated congener of daunorubicin. Doxorubicin intercalates between base pairs in the DNA helix, thereby preventing DNA replication and ultimately inhibiting protein synthesis.

Yoram Devary

This is a Phase 2a, Open-label, one arm study in which the eligible patients will be treated with IV Nerofe, three times a week in 28 days cycles (up to 12 cycles).

Evaluation will include safety procedures, blood level of study drug in certain time points, immune system response and tests checking the mechanism of the drug action.

Nerofe is a first-in-class hormone peptide with cancer suppressive properties. It works in three mechanisms of action. The purpose of this research is to study Nerofe's effect in patients diagnosed with AML and MDS.

2 stage study:

1. Dose Range Finder (4 treatment arms)
2. Dose Confirmation (1 chosen treatment arm)

A Phase 2a, Open-Label, Two Stage Study of Nerofe or Nerofe With Doxorubicin in Subjects With AML or MDS

A Phase 2a, Open-Label, Two Stage Study: Stage A: Dose-Range Finder Study to Assess the Safety and Efficacy of Two Doses of Nerofe and Two Doses of Nerofe in Combination With Doxorubicin in Subjects With Acute Myelogenous Leukemia or High Risk Myelodysplastic Syndrome (AML/High Risk MDS). Stage B: Dose Confirmation Study to Assess the Safety and Efficacy of Nerofe or Nerofe in Combination With Doxorubicin in Subjects With AML/ High Risk MDS

Bone Marrow samples and CBC will be done every 2 cycles

Bone Marrow samples to measure percentage of blasts (%). Range 0-30% (the higher the percentage the worse outcome).

Complete Blood Count (CBC) to measure hemoglobin (g/dL). Range 4-20 (4 worse outcome and 20 best outcome).

Complete Blood Count (CBC) to measure absolute neutrophil count (x10\^9/L). Range 0-15 (the higher the score the better outcome).

Complete Blood Count (CBC) to measure platelets (x10\^9/L). Range 0-2000 (the higher the score the better outcome)

Measuring cytogenetic abnormalities. Range from very good (0) to very poor (4)

Done at Cycle 1 and 2: pre-dose, 15 minutes, 1, 2, 4, 6, 8 and 24 hours.

At Cycle 1 and 2 on Day 1 and Day 15 and on day 1 of each consecutive cycle (up to 12 cycles)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase 1 Trial of Intravenously Administered Nerofe™ in Subjects With Advanced Malignancies	NCT01690741	Cancer	Nerofe	18 Years -	Immune System Key Ltd
NEROFE and Doxorubicin in KRAS-mutated ST2-positive Solid Tumors	NCT05661201	Solid Tumor KRAS Mutation-R...	NEROFE Doxorubicin	18 Years -	Georgetown University
NEROFE and Doxorubicin in KRAS-mutated ST2-positive Solid Tumors	NCT05661201	Solid Tumor KRAS Mutation-R...	NEROFE Doxorubicin	18 Years -	Georgetown University
NEROFE and Doxorubicin in KRAS-mutated ST2-positive Solid Tumors	NCT05661201	Solid Tumor KRAS Mutation-R...	NEROFE Doxorubicin	18 Years -	Georgetown University
A Phase 2a, Open-Label, Two Stage Study of Nerofe or Nerofe With Doxorubicin in Subjects With AML or MDS	NCT03059615	Acute Myelogeno... Myelodysplastic...	Nerofe Doxorubicin	18 Years -	Immune System Key Ltd

Spots Global Cancer Trial Database for nerofe

Every month we try and update this database with for nerofe 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 nerofe

Every month we try and update this database with for nerofe 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 nerofe 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.