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

Regeneron Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Solid Tumors

Treatments: Drug: aflibercept (ziv-aflibercept); Drug: nesvacumab (REGN910/ SAR307746)

Study type: Interventional

Funder types: Industry

Identifiers

NCT01688960

R910-ST-1114

Details and patient eligibility

About

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

Enrollment: 48 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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48 participants in 5 patient groups

Cohort 1

Experimental group

Treatment:

Drug: nesvacumab (REGN910/ SAR307746)

Drug: nesvacumab (REGN910/ SAR307746)

Drug: aflibercept (ziv-aflibercept)

Drug: nesvacumab (REGN910/ SAR307746)

Drug: aflibercept (ziv-aflibercept)

Cohort 2

Experimental group

Treatment:

Drug: nesvacumab (REGN910/ SAR307746)

Drug: nesvacumab (REGN910/ SAR307746)

Drug: aflibercept (ziv-aflibercept)

Drug: nesvacumab (REGN910/ SAR307746)

Drug: aflibercept (ziv-aflibercept)

Cohort 3a

Experimental group

Treatment:

Drug: nesvacumab (REGN910/ SAR307746)

Drug: nesvacumab (REGN910/ SAR307746)

Drug: aflibercept (ziv-aflibercept)

Drug: nesvacumab (REGN910/ SAR307746)

Drug: aflibercept (ziv-aflibercept)

Cohort 3b

Experimental group

Treatment:

Drug: nesvacumab (REGN910/ SAR307746)

Drug: nesvacumab (REGN910/ SAR307746)

Drug: aflibercept (ziv-aflibercept)

Drug: nesvacumab (REGN910/ SAR307746)

Drug: aflibercept (ziv-aflibercept)

Cohort 4

Experimental group

Treatment:

Drug: nesvacumab (REGN910/ SAR307746)

Drug: nesvacumab (REGN910/ SAR307746)

Drug: aflibercept (ziv-aflibercept)

Drug: nesvacumab (REGN910/ SAR307746)

Drug: aflibercept (ziv-aflibercept)