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

Phase 1

Completed

• Conditions: Solid Tumors
• Interventions: Drug: nesvacumab (REGN910/ SAR307746); Drug: aflibercept (ziv-aflibercept)

• Registration Number: NCT01688960
• Lead Sponsor: Regeneron Pharmaceuticals

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-09-17
• Study First Submitted QC: 2012-09-17
• Study First Posted: 2012-09-20
• Study Start: 2012-10
• Primary Completion: 2014-11
• Study Completion: 2014-11
• Status Verified: 2015-03
• Last Update Submitted: 2015-03-16
• Last Update Posted: 2015-03-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 48

Inclusion Criteria

Inclusion criteria include, but are not limited to, the following:

1. Confirmed diagnosis of solid tumor malignancy
2. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
3. Adequate hepatic, renal and bone marrow function
4. 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:

1. Patients with brain metastases, spinal cord compression, carcinomatous meningitis, or other evidence of central nervous system involvement
2. Either systolic BP greater than 140 mm Hg or diastolic BP greater than 90 mm Hg
3. Patients with medical history of myocardial infarction, unstable angina pectoris, coronary/ peripheral artery bypass graft, congestive heart failure or ventricular arrhythmia
4. Patients with deep vein thrombosis or pulmonary embolism within last 3 months
5. Patients with serious non healing wound or acute ulcer
6. 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
7. Patients with history of abdominal or tracheal-esophageal fistula
8. Prior treatment with aflibercept (ziv-aflibercept), Ang2 or Tie2 inhibitors
9. Prior treatment with bevacizumab within last 6 weeks
10. Pregnant or breast-feeding women

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cohort 3b	nesvacumab (REGN910/ SAR307746)	-
Cohort 4	nesvacumab (REGN910/ SAR307746)	-
Cohort 3a	nesvacumab (REGN910/ SAR307746)	-
Cohort 2	nesvacumab (REGN910/ SAR307746)	-
Cohort 2	aflibercept (ziv-aflibercept)	-
Cohort 4	aflibercept (ziv-aflibercept)	-
Cohort 1	nesvacumab (REGN910/ SAR307746)	-
Cohort 1	aflibercept (ziv-aflibercept)	-
Cohort 3a	aflibercept (ziv-aflibercept)	-
Cohort 3b	aflibercept (ziv-aflibercept)	-

Primary Outcome Measures

Name	Time	Method
Maximum Tolerable Dose (MTD) or Recommended Phase 2 Dose (RP2D)	Day 1 to Day 28	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

Secondary Outcome Measures

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