novel immunotherapy strategies for advanced triple negative breast cancer (tnbc) patients: tonic-3 trial

Conditions: Metastatic Breast Cancer

Summary: this is a single center, non-blinded, multi-cohort, non-comparative phase ii trial to study the safety and efficacy of tiragolumab with atezolizumab and/or ipilimumab in advanced triple-negative breast cancer.

programmed cell death protein 1 (pd1) -blockade is currently being approved for the neoadjuvant treatment of early tnbc as well as for first-line treatment in combination with chemotherapy for patients with programmed cell death-ligand 1 (pd-l1) -positive tnbc with metastatic disease. however, response rates are modest, responses are not always durable and pd-l1 is a suboptimal biomarker to select patients for this regimen. therefore, the overarching goal of this tonic-3 study is to develop novel immunomodulatory strategies for patients with advanced tnbc making use state-of-the-art research tools to better understand the underlying cancer-immune interactions of this disease

Eligibility criteria:
inclusion criteria: * metastatic or incurable locally advanced triple negative breast cancer with confirmation of estrogen receptor (er) and human epidermal growth factor receptor 2 (her2) negativity (er \<10%, her2 ihc 0, 1+ or 2+ with no amplification) on a histological biopsy of a metastatic lesion * patients with pd-l1 negative disease determined using the combined positivity score (cps\<10) (dako 22c3 ihc) or previously treated with anti-pd(l)1 in the (neo)adjuvant or metastatic setting (irrespective of pd-l1 status). * metastatic lesion accessible for histological biopsy * 18 years or older * world health organisation (who) performance status of 0 or 1 * maximum of three lines of chemotherapy, including antibody-drug conjugates and poly-adp ribose polymerase (parp)-inhibitors, for metastatic disease and with evidence of progression of disease * measurable or evaluable disease according to recist1.1 * disease free interval (defined as time between first diagnosis or locoregional recurrence and first metastasis) longer than 1 year. this does not apply to patients with de novo metastatic disease or patients who did not receive (neo)adjuvant chemotherapy. * adequate bone marrow, kidney and liver function exclusion criteria: * uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris * symptomatic brain metastases (subjects with asymptomatic brain metastases are eligible if these are free of progression for at least 4 weeks) * history of leptomeningeal disease localization * history of having received other anticancer therapies within 2 weeks of start of the study drug * history of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins * known hypersensitivy to chinese hamster ovary cell products or to any component of the atezolizumab or tiragolumab formulation * history of immunodeficiency, autoimmune disease, conditions requiring immunosuppression (\>10 mg daily prednisone equivalents) or chronic infections. * prior treatment with an anti-ctla4 or anti-tigit antibody. * administration of live vaccine within 30 days of planned start of study therapy. * active other cancer * positive test for hepatitis b, hepatitis c, hiv and/or epstein barr virus (ebv) * history of uncontrolled serious medical or psychiatric illness * current pregnancy pregnancy or breastfeeding.

Keywords: triple negative breast cancer