Glembatumumab Vedotin, Nivolumab, and Ipilimumab in Treating Patients With Advanced Metastatic Solid Tumors That Cannot Be Removed by Surgery

Metastatic Melanoma Clinical Trial

Official title: Phase Ib/II Clinical Trial of Glembatumumab Vedotin and Nivolumab in Advanced Solid Tumors

Status Withdrawn

Clinical Trial Summary

This phase Ib/II trial studies the best dose of glembatumumab vedotin when giving together with nivolumab and ipilimumab in treating patients with solid tumor that has spread to other places in the body and cannot be removed by surgery. Monoclonal antibodies, such as glembatumumab vedotin, nivolumab, and ipilimumab, may interfere with the ability of tumor cells to grow and spread.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To determine the recommended phase 2 dose (RP2D) for the combination of glembatumumab vedotin and nivolumab in patients with solid tumors. (Phase Ib) II. To evaluate the antitumor activity of the combination in 4 expansion cohorts (melanoma, uveal melanoma, GPNMB overexpressing triple negative breast cancer [TNBC], other GPNMB overexpressing solid tumors) as measured by overall response by Immune-Modified Response Evaluation Criteria in Solid Tumors (iRECIST)/Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. (Phase II)

SECONDARY OBJECTIVES:

I. To characterize the safety and toxicity profile of the combination. II. To evaluate the clinical benefit rate (no disease progression within 6 months), progression free survival (PFS), and overall survival (OS) in patients receiving the combination treatment.

III. To evaluate the pharmacokinetics (PK) of glembatumumab vedotin and nivolumab in combination in serum and in mononuclear phagocyte system (MPS) cells in peripheral blood mononuclear cells.

IV. Profile differences in the type, number and density of Fc-receptors (FcgammaR) on MPS cells in blood of patients prior to and after administration of glembatumumab vedotin and nivolumab as a method to evaluate the factors affecting PK and pharmacodynamics (PD) variability and mechanisms of drug-drug interactions.

V. Characterize differences in chemokines (CCL2 and CCL5) and other cytokines in blood of patients prior to and after administration of glembatumumab vedotin and nivolumab as a method to evaluate the factors affecting PK and PD variability and mechanisms of drug-drug interactions.

VI. To evaluate the pharmacodynamic (PD) effects of the combination in plasma and tissue biomarkers.

OUTLINE:

Patients receive glembatumumab vedotin intravenously (IV) over 90 minutes and nivolumab IV over 60 minutes on day 8 of course 1 and on day 1 of subsequent courses. Patients in melanoma expanded cohort also receive ipilimumab IV over 90 minutes on day 1. Treatment with ipilimumab repeats every 21 days for 4 courses in the absence of disease progression or unaccepted toxicity and courses with glembatumumab vedotin and nivolumab repeat every 21 days in the absence of disease progression or unaccepted toxicity.

After completion of study treatment, patients are followed up for 4 weeks and then at 30 and 70 days. ;

Related Conditions & MeSH terms

• Advanced Malignant Solid Neoplasm
• Breast Neoplasms
• Estrogen Receptor Negative
• GPNMB Positive
• HER2/Neu Negative
• Melanoma
• Metastatic Malignant Solid Neoplasm
• Metastatic Melanoma
• Neoplasms
• Progesterone Receptor Negative
• Stage III Breast Cancer AJCC v7
• Stage III Cutaneous Melanoma AJCC v7
• Stage III Uveal Melanoma AJCC v7
• Stage IIIA Cutaneous Melanoma AJCC v7
• Stage IIIB Cutaneous Melanoma AJCC v7
• Stage IIIC Cutaneous Melanoma AJCC v7
• Stage IV Breast Cancer AJCC v6 and v7
• Stage IV Cutaneous Melanoma AJCC v6 and v7
• Stage IV Uveal Melanoma AJCC v7
• Triple Negative Breast Neoplasms
• Triple-Negative Breast Carcinoma
• Unresectable Solid Neoplasm
• Uveal Neoplasms

• NCT number: NCT03326258
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• Start date: April 20, 2018
• Completion date: April 20, 2018