Phase 1 Safety and Tolerability Study of Andes-1537 for Injection in Patients With Advanced Unresectable Solid Tumors

Study Overview
=================
Brief Summary
-----------------
This is a first-in-human, open-label, dose escalation and expansion, 2-part study to determine the safety, tolerability, and maximum tolerated dose of Andes-1537 for Injection in patients with advanced unresectable solid tumors that are refractory to standard therapy or for which no standard therapy is available.

Detailed Description
-----------------
Part 1 is a dose-escalation study to establish the maximum tolerated dose based on dose-limiting toxicities and to evaluate the safety and tolerability of multiple doses of Andes-1537 for Injection in patients with advanced unresectable solid tumors that are refractory to standard therapy or for which no standard therapy is available. Part 2 is an open-label, dose-expansion study to determine the safety, tolerability, and preliminary efficacy of Andes-1537 in patients with advanced solid tumors. In part 2, patients will be enrolled and receive the recommended phase 2 dose established in part 1 based on the safety, tolerability, pharmacokinetics, and preliminary efficacy data.

Official Title
-----------------
A Phase 1 Open-label First-in-human Dose-escalating Safety and Tolerability Study Evaluating Subcutaneous Administration of Andes-1537 for Injection in Patients With Advanced Unresectable Solid Tumors That Are Refractory to Standard Therapy or For Which No Standard Therapy is Available

Conditions
-----------------
Advanced Unresectable Solid Tumors

Intervention / Treatment
-----------------
* Drug: Andes-1537 for Injection


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Men and women 18 years of age or older Can understand and voluntarily sign an informed consent form prior to any study-related assessments or procedures, and are able to adhere to the study visit schedule and other protocol requirements Patient with documented pathological evidence of a cancer from which has developed advanced unresectable solid tumors that are, in the opinion of their treating physician, refractory to standard therapy or for which no standard therapy is available Consent to tumor biopsy from accessible tissue (optional in Part 1 and mandatory in Part 2) Have measureable disease by RECIST Have Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 Have adequate organ function, confirmed by the following laboratory values obtained ≤ 3 days prior to the first treatment: absolute neutrophil count ≥ 1.5 × 10^9/L; hemoglobin ≥ 9 g/dL; platelets ≥ 100 × 10^9/L; aspartate transaminase and alanine transaminase ≤ 2.5 × upper limit of normal (ULN); serum total bilirubin ≤ 2.0 × ULN; serum creatinine ≤ 1.5 × ULN, or estimated or measured creatinine clearance ≥ 60 mL/min; prothrombin time, activated partial thromboplastin time ≤ 1.5 × ULN if not on anticoagulation therapy Female patients of childbearing potential must have a negative serum pregnancy test and be using adequate contraception prior to study entry and must agree to use adequate contraception from study entry through at least 6 months after discontinuation of study drug. Male patients at screening must agree to practice adequate contraception from study entry through at least 6 months after discontinuation of study drug. Exclusion Criteria: Have symptomatic central nervous system metastases. Patients with brain metastases that have been previously treated and are stable for ≥ 4 weeks or treated with gamma knife surgery and are stable for ≥ 2 weeks are allowed to enter the study. Have unstable angina, clinically significant cardiac arrhythmia, New York Heart Association Class 3 or 4 congestive heart failure, or prolonged QT interval corrected wave of greater than 470 ms. Receiving treatment with any medication known to produce QT prolongation within 7 days of study entry Have had prior systemic chemotherapy treatments or investigational modalities ≤ 5 half-lives or 4 weeks, whichever is shorter, prior to starting treatment with Andes-1537 or who have not recovered from side effects, grade 2 or greater, of such therapy (except alopecia) Have had major surgery ≤ 2 weeks prior to starting treatment with Andes-1537 or who have not recovered from side effects of such surgery Are pregnant or breastfeeding Have had DVT or venous thromboembolism within 6 weeks of study entry Have active uncontrolled bleeding or a known bleeding disorder Have any serious or unstable concomitant systemic conditions that are incompatible with this clinical study, including but not limited to substance abuse, psychiatric disturbance, or uncontrolled intercurrent illness (including active infection), arterial thrombosis, or symptomatic pulmonary embolism Have a known sensitivity to any of the components of Andes-1537 Are unable or unwilling to follow protocol instructions and requirements

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: Andes-1537 for Injection<br>Part 1 is an open-label, dose-escalation study. Part 2 is an open-label, dose-expansion study. | Drug: Andes-1537 for Injection<br>* Part 1: Andes-1537 subcutaneous injection, 100 to 1000 mg twice a week per 4-week cycle Part 2: Andes-1537 subcutaneous injection, recommended phase 2 dose administered twice a week per 4-week cycle<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of dose-limiting toxicities | Determine maximum tolerated dose | First 4-week treatment cycle | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | Incidence of treatment-emergent adverse events | Safety evaluations will be measured through 28 days after last dose of Andes-1537 | 
| Safety laboratory tests | Changes in baseline safety laboratory tests | Safety evaluations will be measured through 28 days after last dose of Andes-1537 | 
| Physical examinations | Changes in baseline physical examination | Safety evaluations will be measured through 28 days after last dose of Andes-1537 | 
| Vital signs | Changes in baseline vital signs | Safety evaluations will be measured through 28 days after last dose of Andes-1537 | 
| 12-lead electrocardiogram (ECG) | Changes in baseline ECG | First 4-week treatment cycle | 
| Injection site reactions | Incidence of injection site reactions | Safety evaluations will be measured through 28 days after last dose of Andes-1537 | 
| Pharmacokinetic parameters in Andes-1537 in blood and urine for single-dose and multiple-dose evaluation | Measure maximum concentration, time to maximum concentration, area under the curve, clearance, volume of distribution, and half-life | Pre-treatment, following first dose and last dose of cycle 1 (4-week cycle), first dose of each additional cycle through study completion, and last visit | 
| Pharmacodynamic parameters in blood and biopsy samples from accessible tissue | Evaluate biomarkers in tissue and blood | Pre-treatment and at 4 and 8 weeks for biopsy; blood samples at pre-treatment, every 8 weeks, and last visit | 
| Objective response rate by Response Evaluation Criteria in Solid Tumors (RECIST) with CT or MRI scan | Changes in tumor size from baseline measurements | Every 8 weeks following completion of 2 treatment cycles to cover from date of initiation until date of first documented progression or toxicity to Andes-1537, which ever comes first | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Neoplasms, Solid Tumors, Advanced Malignancy, Cancer