NCT02129556

Anti-PD-1 Monoclonal Antibody in Advanced, Trastuzumab-resistant, HER2-positive Breast Cancer

A Phase Ib/II Trial Evaluating the Efficacy of MK-3475 and Trastuzumab in Patients With Trastuzumab-resistant, HER2-positive Metastatic Breast Cancers

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 58 (actual)
• Sponsor: ETOP IBCSG Partners Foundation · Network
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Panacea is a phase Ib/II trial evaluating the efficacy of MK-3475 and trastuzumab in patients with trastuzumab-resistant, HER2- positive metastatic breast cancers

Detailed description

A significant amount of preclinical and correlative clinical data suggest that HER2-positive breast cancer could be amenable to immune¬therapeutic approaches. The presence of HER2-overexpression in breast cancers is associated with higher levels of proliferation, high histologic grade and higher levels of tumor infiltrating lymphocytes (TILs) compared with HER2-negative tumors. The investigators therefore hypothesize that for HER2-positive tumors, avoidance of destruction by the host immune system must be an important mechanism contributing to tumor growth and progression. The term "immune evasion" refers to the ability of the tumor to suppress and change host anti-tumor immune reactions. The programmed cell death 1 (PD-1) pathway represents a major immune control switch which may be engaged by tumor cells to overcome active T-cell immune surveillance. The ligands for PD-1 (PD-L1 and PD-L2) are constitutively expressed or can be induced in various tumors. High expression of PD-L1 on tumor cells (and to a lesser extent of PD-L2) has been found to correlate with poor prognosis and survival in various other solid tumor types. Furthermore, PD-1 has been suggested to regulate tumor-specific T-cell expansion in patients with malignant melanoma. These observations suggest that the PD-1/PD-L1 pathway plays a critical role in the tumor immune evasion and could be considered an attractive target for therapeutic intervention in several solid organ types. MK-3475 (previously known as SCH 900475) is a potent and highly-selective humanized mAb of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. MK-3475 strongly enhances T lymphocyte immune responses in cultured blood cells from healthy human donors, cancer patients, and primatesMK-3475 also modulates the level of interleukin-2 (IL-2), tumor necrosis factor alpha (TNFα), interferon gamma (IFNγ), and other cytokines. The investigators therefore propose to evaluate if the addition of an immunotherapy can reverse trastuzumab resistance and improve clinical outcomes in HER2-positive disease. In this study the investigators will determine if a monoclonal antibody targeted against PD-1, a T cell negative regulator, can reverse trastuzumab resistance in patients previously progressing on trastuzumab.

Conditions

• Metastatic Breast Cancer

Interventions

Type	Name	Description
DRUG	MK-3475	The phase Ib trial will determine the recommended dose from three MK-3475 dose levels: 1mg/kg, 2 mg/kg or 10 mg/kg.

Timeline

• Start date: 2014-12-01
• Primary completion: 2017-08-04
• Completion: 2017-08-04
• First posted: 2014-05-02
• Last updated: 2019-02-15
• Results posted: 2019-02-15

Locations

11 sites across 5 countries: Australia, Austria, Belgium, France, Italy