NCT03409198

Phase IIb Study Evaluating Immunogenic Chemotherapy Combined With Ipilimumab and Nivolumab in Breast Cancer

A Randomized Phase IIb Study Evaluating Immunogenic Chemotherapy Combined With Ipilimumab and Nivolumab in Patients With Metastatic Hormone Reseptor Positive Breast Cancer

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 82 (actual)
• Sponsor: Oslo University Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Breast cancer is rarely curable after metastasis, and the therapeutic options are limited. Interestingly, the host immune response is strongly predictive for the effect of chemotherapy in subgroups of patients with breast cancer. The aim is to release the brake on the immune response by use of ipilimumab, which blocks CTLA-4 and may deplete regulatory T cells, combined with nivolumab (anti PD1). Importantly, it is possible that non-responders to nivolumab/ipilimumab (nivo/ipi) can be turned responders by use of immunogenic chemotherapy.

Detailed description

There is compelling evidence from animal studies, supported by data from humans, that some chemotherapeutic agents are immunogenic. Doxorubicin and cyclophosphamide have been shown to be particularly powerful inducers of immunogenic cell death. Both agents fulfil 5/5 criteria established for assessing the immunogenicity of different chemotherapeutic drugs. There is also strong evidence from humans, particularly in breast cancer, indicating that the clinical effect of doxorubicin and cyclophosphamide depends on the host immune response. Further, these agents have been shown to induce a Type I interferon immune response in breast cancer. Taken together, there is a strong rationale for synergy between doxorubicin/cyclophosphamide and PD-1/CTLA-4 blockade. The trial combines nivolumab and ipilimumab with established 1st choice chemotherapy in patients with metastatic hormone reseptor positive breast cancer. Nivolumab/ipilimumab (nivo/ipi) may i) potentiate the patient´s spontaneous anti-tumor immune response ii) synergize with chemotherapeutic agents that induce immunological cell death

Conditions

• Breast Cancer
• Hormone Receptor Positive Tumor
• Metastatic Breast Cancer

Interventions

Type	Name	Description
DRUG	Ipilimumab	Ipilimumab blocks CTLA-4 and may deplete regulatory T cells
DRUG	Nivolumab	Nivolumab blocks PD-1 and thereby enhances the effector phase of the immune reaction, by enabling T cells to kill tumor cells and engage effectively with other PD-L1 expressing targets.
DRUG	Pegylated liposomal doxorubicin	Chemotherapy
DRUG	Cyclophosphamide	Chemotherapy

Timeline

• Start date: 2018-01-21
• Primary completion: 2022-05-11
• Completion: 2022-05-11
• First posted: 2018-01-24
• Last updated: 2024-10-15

Locations

6 sites across 2 countries: Belgium, Norway