Resources Marleen Kok Group
Marleen Kok is the (co) principal investigator of several investigator-initiated clinical trials, focusing on the improvement of immunotherapy for breast cancer patients. These trials have a large translational research component, aiming to gain a better understanding of the cancer-immune interactions in breast cancer and identify potential novel treatment options for these patients.
In the BELLINI-trial, we aim to study the efficacy and biological effects of short-term neo-adjuvant immunotherapy in patients with early-stage hormone sensitive breast cancer (ER+/HER2-) or hormone insensitive breast cancer (triple negative, ER-/PR-/HER2-). Patients will be treated with 2 cycles of nivolumab (anti-PD1) or a combination of nivolumab and ipilimumab (anti-CTLA4), followed by neo-adjuvant chemotherapy or surgery.
The GELATO-trial is a multicenter, phase-II study, evaluating the efficacy of immunotherapy in patients with metastatic lobular breast cancer. Patients receive 12 cycles of weekly (low-dose) carboplatin, from the third cycle onwards atezolizumab (anti-PDL1) is added every 3 weeks. Biopsies and peripheral blood are taken before the start of treatment, after 2 cycles of carboplatin and after 2 cycles of atezolizumab to study the intratumoral and systemic effects of carboplatin alone and in combination with atezolizumab.
In the MIMOSA-trial, we investigate the efficacy and safety of trastuzumab in combination with monalizumab (anti-NKG2A) in patients with metastatic HER2-positive breast cancer with progressive disease after previous trastuzumab treatment. Monalizumab targets the NK2GA checkpoint present on both NK cells and CD8 T cells. By combining monalizumab with trastuzumab, we hypothesize that monalizumab can enhance the immunological effects of trastuzumab and thereby unleash NK and CD8 T cells.
The TONIC-2 trial aims to improve responses to immunotherapy in patients with metastatic, triple negative breast cancer by priming the tumor microenvironment before the administration of immunotherapy. In the current cohorts, nivolumab (anti-PD1) monotherapy is administered with or without a two-week induction treatment with weekly cisplatin. Biopsies and peripheral blood are taken before the start of treatment, after 1 cycle of nivolumab or 2 cycles of cisplatin and after 3 cycles of nivolumab to study the immunological effects of cisplatin and the enhancement of these effects by nivolumab.
In the TONIC-trial, patients with metastatic triple-negative breast cancer were randomized between nivolumab without induction treatment or one of four immune induction treatments (irradiation, cisplatin, doxorubicin, cyclophosphamide) followed by nivolumab The results of the first stage of the trial were published in 2019 in Nature Medicine. It was found that doxorubicin and cisplatin may induce a more favorable tumor microenvironment and might increase the likelihood of response to nivolumab. Based on these results, the doxorubicin cohort was expanded in the second stage of the TONIC-trial and the cisplatin cohort is further expanded in the TONIC-2 trial.
The TRIPLE-B trial aims to identify an effective first-line treatment regimen in patients with metastatic or locally advanded incurable triple negative breast cancer. Patients are randomized between carboplatin/cyclophosphamide versus paclitaxel with or without the addition of atezolizumab (anti-PD-L1). Furthermore, the value of the BRCA1-like test to predict for a differential benefit from carboplatin / cyclophosphamide compared to paclitaxel (with or without atezolizumab) will be validated in these patients.