Nesvacumab (REGN910/ SAR307746) and Aflibercept (Ziv-aflibercept in the U.S.) in Patients With Advanced Solid Malignancies

Study Overview
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Brief Summary
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This is an open-label, multicenter, ascending, multiple dose study of nesvacumab (REGN910/ SAR307746) in combination with aflibercept (ziv-aflibercept in the U.S.)

Official Title
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A Phase 1b Study of Combined Angiogenesis Inhibition by Administering REGN910 and Aflibercept (Ziv-aflibercept) in Patients With Advanced Solid Malignancies

Conditions
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Solid Tumors

Intervention / Treatment
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* Drug: nesvacumab (REGN910/ SAR307746)
* Drug: nesvacumab (REGN910/ SAR307746)
* Drug: nesvacumab (REGN910/ SAR307746)
* Drug: aflibercept (ziv-aflibercept)
* Drug: aflibercept (ziv-aflibercept)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion criteria include, but are not limited to, the following: Confirmed diagnosis of solid tumor malignancy Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Adequate hepatic, renal and bone marrow function Resolution of toxicity from prior therapy (except alopecia) to grade less than or equal to 1 Exclusion Criteria: Exclusion criteria include, but are not limited to, the following: Patients with brain metastases, spinal cord compression, carcinomatous meningitis, or other evidence of central nervous system involvement Either systolic BP greater than 140 mm Hg or diastolic BP greater than 90 mm Hg Patients with medical history of myocardial infarction, unstable angina pectoris, coronary/ peripheral artery bypass graft, congestive heart failure or ventricular arrhythmia Patients with deep vein thrombosis or pulmonary embolism within last 3 months Patients with serious non healing wound or acute ulcer Patients with treatment resistant or bleeding peptic ulcer disease, erosive esophagitis or gastritis, grade 3 or gastrointestinal bleeding/hemorrhage, infectious or inflammatory bowel disease, diverticulitis, or other uncontrolled thromboembolic event within last 3 months Patients with history of abdominal or tracheal-esophageal fistula Prior treatment with aflibercept (ziv-aflibercept), Ang2 or Tie2 inhibitors Prior treatment with bevacizumab within last 6 weeks Pregnant or breast-feeding women

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: Cohort 1<br> | Drug: nesvacumab (REGN910/ SAR307746)<br>* Dose level 1<br>Drug: aflibercept (ziv-aflibercept)<br>* Dose level 1<br>* Other names: In US: aflibercept is known as ziv-aflibercept;|
| Experimental: Cohort 2<br> | Drug: nesvacumab (REGN910/ SAR307746)<br>* Dose level 2<br>Drug: aflibercept (ziv-aflibercept)<br>* Dose level 1<br>* Other names: In US: aflibercept is known as ziv-aflibercept;|
| Experimental: Cohort 3a<br> | Drug: nesvacumab (REGN910/ SAR307746)<br>* Dose level 3<br>Drug: aflibercept (ziv-aflibercept)<br>* Dose level 1<br>* Other names: In US: aflibercept is known as ziv-aflibercept;|
| Experimental: Cohort 3b<br> | Drug: nesvacumab (REGN910/ SAR307746)<br>* Dose level 2<br>Drug: aflibercept (ziv-aflibercept)<br>* Dose level 2<br>* Other names: In US: aflibercept is known as ziv-aflibercept;|
| Experimental: Cohort 4<br> | Drug: nesvacumab (REGN910/ SAR307746)<br>* Dose level 3<br>Drug: aflibercept (ziv-aflibercept)<br>* Dose level 2<br>* Other names: In US: aflibercept is known as ziv-aflibercept;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerable Dose (MTD) or Recommended Phase 2 Dose (RP2D) | Determine the maximum tolerable dose or recommended phase 2 dose of nesvacumab (REGN910/ SAR307746) administered in combination with aflibercept (ziv-aflibercept) in patients with advanced solid malignancies | Day 1 to Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK) | To assess PK parameters such as concentration of nesvacumab (REGN910/ SAR307746) and aflibercept (ziv-aflibercept). | Day 1 to Day 170 | 
| Immunogenicity | To assess the anti-drug antibodies of nesvacumab (REGN910/ SAR307746) and aflibercept (ziv-aflibercept) | Day 1 to Day 170 | 
| Antitumor activity | Objective tumor response according to RECIST (Response Evaluation Criteria in Solid Tumors) version 1.1 | Day 1 to Day 170 | 
| Pharmacodynamics (PD) | Target inhibition biomarker changes, serum tumor markers | Day 1 to Day 170 |