ALICE
A randomized placebo-controlled phase II study evaluating atezolizumab combined with immunogenic chemotherapy in patients with metastatic triple-negative breast cancer
PI: JA Kyte
We conduct a randomized, placebo-controlled phase IIb study (ALICE) evaluating anti-PDL1 (atezolizumab) combined with immunogenic chemotherapy in patients with metastatic triple-negative breast cancer (mTNBC). TNBC is the most aggressive form of breast cancer, does not respond to endocrine/targeted therapies and is incurable after metastasis (median survival ~13 months). The host immune response is strongly predictive for the effect of chemotherapy against TNBC. We will enhance this immune response by use of atezolizumab which has a favourable safety profile and has shown clinical activity against TNBC. In ALICE, we utilize chemotherapy for inducing immunogenic cell death, which represents a personalized in vivo vaccination covering the entire repertoire of antigens expressed in each individual tumor. Such antigen release does not necessarily lead to an effective immune response. However, the chemotherapeutic agents chosen in ALICE, Caelyx (pegylated liposomal doxorubicin) and cyclophosphamide, induce “danger signals” that trigger the immune system. The prospect of clinical benefit from PD-L1-blockade is probably best in patients that have not received multiple previous lines of chemotherapy. We therefore test atezolizumab in 1st/2nd line.
Study design and objectives
ALICE is a randomized, double-blind, placebo-controlled phase IIb study evaluating the efficacy and safety of atezolizumab when combined with immunogenic chemotherapy in subjects with metastatic TNBC. A total of 75 patients will be included and randomized 2:3, as follows:
- Arm A (n=30): Chemo (Caelyx + cyclophosphamide) + placebo
- Arm B (n=45): Chemo (Caelyx + cyclophosphamide) + atezolizumab
Primary objectives:
- Assessment of clinical response: Progression-free survival
- Assessment of toxicity of combined treatment with atezolizumab and chemotherapy
Secondary objectives:
- Assessment of clinical response: Overall tumor response rate (ORR), duration of response (DR), durable tumor response rate (DRR; >6 months), overall survival (OS)
- Assessment of immunological response
- Assessment of health-related quality of life
- Identification of biomarkers for clinical response, toxicity and immune response
- Characterization of tumor evolution and changes in immunological milieu induced by the combination therapy (atezolizumab+chemo), as compared to chemo only