Metastatic triple negative breast cancer has poor prognosis and limited treatment options. Immunotherapy with anti-PD-L1 monoclonal antibodies has shown promising results in several types of cancer including triple negative breast cancer. We have initiated a clinical trial to test the safety and efficacy of a combination of the investigational anti-PD-L1 monoclonal antibody durvalumab and paclitaxel for the treatment of metastatic breast cancer. The rationale behind this trial is that treatment with paclitaxel correlates with development of tumor infiltrating lymphocytes (Demaria et al. 2001; Sardella et al. 2006), and the upregulation of PD-L1 on tumor cells. On the other hand, response to targeted anti-PD-L1 therapy correlates with the level of expression of PD-L1 on tumor cells and the pre-existing tumor immunity like CD8+ infiltrating cells and type I helper CD4+ activated lymphocytes (Herbst, Soria et al. 2014). In addition, PD-L1 has anti-apoptotic function that its blockade will synergize with the apoptotic effect of chemotherapeutic agents like paclitaxel. Therefore, the combination of these two agents is likely to be synergistic.
The treatment is designed to start with one cycle of paclitaxel alone to enhance the immunogenicity and immune cell infiltration followed by the combination of the two agents. Paclitaxel will be delivered weekly on days 1, 8 and 15 of each 28 days cycle while Durvalumab will be given every two weeks (Days 1 and 15 of each cycle). Paclitaxel is given for 6 cycles only while Durvalumab is given until disease progression, or unacceptable toxicity. The primary endpoint of the study is to measure safety and tolerability of the combination while the secondary endpoints include efficacy monitoring.
Clinical trial identification
Legal entity responsible for the study
T. Al‐Tweigeri, M.D.
This clinical trial is an investigator-initiated trial sponsored partially by AstraZeneca as an externally sponsored research (ESR 14 10649).
All authors have declared no conflicts of interest.