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

Solid Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01688960
• Other study ID #: R910-ST-1114
• Status: Completed
• Phase: Phase 1
• First received: September 17, 2012
• Last updated: March 16, 2015
• Start date: October 2012
• Est. completion date: November 2014

Study information

• Verified date: March 2015
• Source: Regeneron Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health CanadaUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: November 2014
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Solid Tumors

Intervention

Drug:
• nesvacumab (REGN910/ SAR307746)
Dose level 1
• nesvacumab (REGN910/ SAR307746)
Dose level 2
• nesvacumab (REGN910/ SAR307746)
Dose level 3
• aflibercept (ziv-aflibercept)
Dose level 1
• aflibercept (ziv-aflibercept)
Dose level 2

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals	Sanofi

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	Pharmacokinetics (PK)	To assess PK parameters such as concentration of nesvacumab (REGN910/ SAR307746) and aflibercept (ziv-aflibercept).	Day 1 to Day 170	No
Secondary	Immunogenicity	To assess the anti-drug antibodies of nesvacumab (REGN910/ SAR307746) and aflibercept (ziv-aflibercept)	Day 1 to Day 170	No
Secondary	Antitumor activity	Objective tumor response according to RECIST (Response Evaluation Criteria in Solid Tumors) version 1.1	Day 1 to Day 170	No
Secondary	Pharmacodynamics (PD)	Target inhibition biomarker changes, serum tumor markers	Day 1 to Day 170	No