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

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.

Timeline

Start

2018-01-21

Primary completion

2022-05-11

Completion

2022-05-11

Outcome

Missed primary endpoint

paper with HR 0.94 (95% CI 0.59 to 1.51). PMID 38242720 ↗

paper The addition of ipi/nivo to chemotherapy increased toxicity without improving efficacy. PMID 38242720 ↗

Publications

• Results Andresen NK, Rossevold AH, Quaghebeur C, Gilje B, Boge B, Gombos A, Falk RS, Mathiesen RR, Julsrud L, Garred O, Russnes HG, Lereim RR, Chauhan SK, Lingjaerde OC, Dunn C, Naume B, Kyte JA. Ipilimumab and nivolumab combined with anthracycline-based chemotherapy in metastatic hormone receptor-positive breast cancer: a randomized phase 2b trial. J Immunother Cancer. 2024 Jan 19;12(1):e007990. doi: 10.1136/jitc-2023-007990.
• Kyte JA, Andresen NK, Russnes HG, Fretland SO, Falk RS, Lingjaerde OC, Naume B. ICON: a randomized phase IIb study evaluating immunogenic chemotherapy combined with ipilimumab and nivolumab in patients with metastatic hormone receptor positive breast cancer. J Transl Med. 2020 Jul 3;18(1):269. doi: 10.1186/s12967-020-02421-w.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Ipilimumab	Monoclonal antibody	1 mg/kg	Intravenous
Subject	Nivolumab	Monoclonal antibody	240 mg	Intravenous
Background	Cyclophosphamide	Other / unclassified	50 mg	Oral
Background	Doxorubicin	Other / unclassified	20 mg/m2	Intravenous

Indications