Dose Escalation Study of NKP-1339 to Treat Advanced Solid Tumors

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine the safety and maximal tolerated dose of NKP-1339, a ruthenium containing compound administered intravenously on a weekly schedule, in patients with advanced solid tumors. The responses to treatment in this population will be evaluated. In addition, the PD and PK properties of the compound will be explored.

Detailed Description
-----------------
NKP-1339 is a novel GRP78 targeted ruthenium based anti-cancer compound which is intravenously administered. GRP78 is a key regulator of misfolded protein processing, which is unregulated in cancer cells. In nonclinical anti-tumor studies, NKP-1339 showed activity against many tumor types, including those resistant to platinum and other standard anti-cancer agents. This Phase I trial evaluates the safety, tolerability, maximum tolerated dose, pharmacokinetics, and pharmacodynamics of NKP-1339.

Official Title
-----------------
A Phase I Dose Escalation Study of NKP-1339 Administered on Days 1, 8 and 15 of Each 28-Day Cycle in Patients With Advanced Solid Tumors Refractory to Treatment

Conditions
-----------------
Solid Tumors

Intervention / Treatment
-----------------
* Drug: NKP-1339


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients ≥ 18 years with histologically or cytologically confirmed advanced solid tumors refractory to standard therapies who have signed an IRB approved Informed Consent Form (ICF). ECOG PS 0 or 1. Adequate hematologic, hepatic and renal function Minimum life expectancy ≥ 12 weeks Exclusion Criteria: No supplemental Iron, i.e., therapeutic or as part of a multivitamin regimen. No chemotherapy, immunotherapy, or radiotherapy for < 4 weeks, BMTs < 9 months or major surgery < 3 weeks. No symptomatic central nervous system metastases. No primary brain tumors or known brain metastasis unless clinically stable and on stable or reducing dose of steroids. No evidence of ischemia, MI within the past 6 months, or other significant abnormality on ECG. No clinically significant active infection including HIV, hepatitis B, or hepatitis C. No Peripheral neuropathy ≥ Grade 2

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NKP-1339<br>NKP-1339 will be administered in single patient cohorts until ≥ Grade 2 toxicity encountered, at which time cohorts converted to a standard 3 + 3 dose escalation scheme. When MTD is reached, an expanded cohort of up to 25 patients will be enrolled at the MTD. | Drug: NKP-1339<br>* NKP-1339 is administered as a 30-90 minute IV infusion (based on volume to be infused) on days 1, 8, and 15 of a 28 day cycle.<br>* Other names: IT-139;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with related adverse events | The incidence and severity of related adverse events and laboratory abnormalities will be used to assess the safety and tolerability of NKP-1339. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of pharmacokinetics | Plasma and urine samples will be analyzed to determine Cmax, Tmax, AUC, terminal elimination rate, elimination half-life, clearance,and volume of distribution. | 0, 0.25, 0.5, 1, 2, 4, 6, 10 and 24 hours | 
| To report any responses to NKP-1339 in subjects with advanced tumors | Tumor assessments every 2 cycles if patients continue treatment beyond 2 Cycles. Treatment is allowed beyond 2 cycles in patients who achieved at least stable disease, at the discretion of investigator and consent of the patient. | >8 weeks | 
| To explore pharmacodynamic endpoints which may be of use in the further development of NKP-1339 | Transferrin, transferrin receptor and GRP-78 in plasma. | 8 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Phase 1, advanced solid tumors