Safety And PK Study Of CVX-060 In Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety and tolerability of CVX-060 in patients with advanced solid tumors.

Official Title
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A Phase 1, Multicenter, Open-label, Dose-escalation, Safety, Pharmacokinetic, And Pharmacodynamic Trial Of Cvx-060, A Selective Angiopoietin-2 (Ang-2) Binding, Anti-angiogenic Covx-body, In Patients With Advanced Solid Tumors

Conditions
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Advanced Solid Tumors, Neoplasms, Carcinoma, Cancer, Malignancy

Intervention / Treatment
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* Biological: CVX-060


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed advanced solid tumors unresponsive to currently available therapies or for which there is no standard therapy. Adequate coagulation, liver, and renal function. Candidate for DCE-MRI evaluations. ECOG (Eastern Cooperative Oncology Group) performance status of 0 or 1. Exclusion Criteria: Evidence of significant bleeding problems. History of certain gastrointestinal problems including fistula and abscess. Chronic, uncontrolled hypertension. Patients with any history of primary or metastatic tumor involvement of the brain or with tumors that encase great vessels.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Biological: CVX-060<br>* Weekly, intravenous dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) | Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. Relatedness to CVX-060 was assessed by the investigator (Yes/No). Participants with multiple occurrences of an AE within a category were counted once within the category. | Baseline (Day 0) up to 30 days after last dose of study medication | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Serum Concentration (Cmax) |  | 0 hour (pre-dose) on Day 0 up to Day 7 of cycle 1 (28 days cycle) | 
| Serum Decay Half-Life (t1/2) | Serum decay half-life is the time measured for the serum concentration to decrease by one half. | 0 hour (pre-dose) on Day 0 up to Day 7 of cycle 1 (28 days cycle) | 
| Area Under the Curve From Time Zero to 168 Hours [AUC (0-168)] | AUC (0-168)= Area under the serum concentration versus time curve from time zero (pre-dose) to 168 hours after dosing (Day 7). | 0 hour (pre-dose) on Day 0 up to Day 7 of cycle 1 (28 days cycle) | 
| Apparent Volume of Distribution (Vss) | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after intravenous infusion dose (Vss) is influenced by the fraction absorbed. | 0 hour (pre-dose) on Day 0 up to Day 7 of cycle 1 (28 days cycle) | 
| Apparent Clearance (CL) | Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood (rate at which a drug is metabolized or eliminated by normal biological processes). Clearance obtained after intravenous infusion dose (apparent clearance) is influenced by the fraction of the dose absorbed. | 0 hour (pre-dose) on Day 0 up to Day 7 of cycle 1 (28 days cycle) | 
| Time to Reach Maximum Observed Serum Concentration (Tmax) |  | 0 hour (pre-dose) on Day 0 up to Day 7 of cycle 1 (28 days cycle) | 
| Recommended Phase 2 Dose (RP2D): Stage 1 | RP2D was determined as the highest dose where none out of 3 (0/3) or less than or equal to 1 out of 6 (<=1/6) participants experienced a dose limiting toxicity (DLT) or was determined based on the safety, pharmacokinetic, and pharmacodynamic findings. DLT was first course AE defined based on National Cancer Institute common toxicity criteria for adverse events version 3 (NCI-CTCAE Version 3) as any hematologic or non-hematologic toxicity greater than or equal to (>=) Grade 3. | Baseline (Day 0) up to 42 days after the last dose of study medication | 
| Number of Participants With Anti-CVX-060 Antibodies |  | Baseline (Day 0) up to 42 days after last dose | 
| Number of Samples From Participants With Anti-CVX-060 Antibodies |  | Baseline (Day 0) up to 42 days after last dose | 
| Number of Participants With Best Overall Response (BOR) | BOR: best response recorded from treatment start until disease progression/recurrence based on Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response (CR): disappearance of all lesions. Partial Response (PR): >=30% decrease in sum of longest diameters (SLDs) of target lesions taking as reference baseline SLDs, associated to non-progressive disease (non-PD) response for non-target (NT) lesions. PD: >=20% increase in SLDs of target lesions taking as reference smallest SLDs since treatment start, or appearance of >=1 new lesion, or unequivocal progression in NT lesions. Stable disease (SD): neither shrinkage for CR/PR nor increase for PD taking as reference smallest SLDs since treatment start. CR and PR had to be confirmed on a follow up imaging assessment >=4 weeks after initial objective documentation of response. SD criteria should be met at least once after start of treatment in a minimum interval of 8 weeks. Participants with >=3 treatments cycles were reported. | Day 0 (predose), assessed every 8 weeks (2 cycles) until disease progression, unacceptable toxicity, or withdrawal for other reasons (up to Week 133) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 1, Tumors, CVX-060