A Phase Ib study evaluating MNRP1685A, a fully human anti-NRP1 monoclonal antibody, in combination with bevacizumab and paclitaxel in patients with advanced solid tumors
Related Experiment Video
Updated: May 2, 2026
Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma
Published on: October 27, 2014
Amita Patnaik1, Patricia M LoRusso, Wells A Messersmith
1South Texas Accelerated Research Therapeutics, 4383 Medical Drive, San Antonio, TX, 78229, USA, amita.patnaik@start.stoh.com.
Purpose:
MNRP1685A is a human monoclonal antibody that blocks binding of vascular endothelial growth factor (VEGF), VEGF-B, and placental growth factor 2 to neuropilin-1 resulting in vessel immaturity and VEGF dependency. The safety of combining MNRP1685A with bevacizumab, with or without paclitaxel, was examined.
Methods:
Patients with advanced solid tumors received escalating doses of MNRP1685A (7.5, 15, 24, and 36 mg/kg) with bevacizumab 15 mg/kg every 3 weeks in Arm A (n = 14). Arm B (n = 10) dosing consisted of MNRP1685A (12 and 16 mg/kg) with bevacizumab 10 mg/kg (every 2 weeks) and paclitaxel 90 mg/m(2) (weekly, 3 of 4 weeks). Objectives were to determine safety, pharmacokinetics, pharmacodynamics, and the maximum tolerated dose of MNRP1685A.
Results:
Infusion reactions (88 %) and transient thrombocytopenia (67 %) represent the most frequent study drug-related adverse events (AEs). Drug-related Grade 2 or 3 proteinuria occurred in 13 patients (54 %). Additional study drug-related AEs occurring in >20 % of patients included neutropenia, alopecia, dysphonia, fatigue, and nausea. Neutropenia occurred only in Arm B. Grade ≥3 study drug-related AEs in ≥3 patients included neutropenia (Arm B), proteinuria, and thrombocytopenia. Two confirmed and three unconfirmed partial responses were observed.
Conclusions:
The safety profiles were consistent with the single-agent profiles of all study drugs. However, a higher than expected rate of clinically significant proteinuria was observed that does not support further testing of MNRP1685A in combination with bevacizumab.
Insights
This study evaluated the safety of combining MNRP1685A with bevacizumab, finding infusion reactions and thrombocytopenia as common adverse events. High rates of proteinuria suggest this combination is not suitable for further clinical trials.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- MNRP1685A is a monoclonal antibody targeting neuropilin-1, inhibiting VEGF, VEGF-B, and PlGF-2.
- This inhibition leads to vessel immaturity and VEGF dependency in tumors.
Purpose of the Study:
- To assess the safety of combining MNRP1685A with bevacizumab.
- To evaluate combinations with or without paclitaxel.
- To determine safety, pharmacokinetics, pharmacodynamics, and maximum tolerated dose of MNRP1685A.
Main Methods:
- Two arms evaluated escalating doses of MNRP1685A with bevacizumab.
- Arm B additionally included paclitaxel.
- Safety, pharmacokinetics, and pharmacodynamics were primary objectives.
Main Results:
- Most frequent adverse events included infusion reactions (88%) and thrombocytopenia (67%).
- Clinically significant proteinuria (Grade 2/3) occurred in 54% of patients.
- Other AEs: neutropenia, alopecia, dysphonia, fatigue, nausea. Two partial responses were observed.
Conclusions:
- Safety profiles were consistent with individual drug profiles.
- A higher-than-expected rate of proteinuria was observed.
- Further testing of MNRP1685A in combination with bevacizumab is not supported.
