Metastatic Breast Cancer
Conditions
Keywords
Triple negative breast cancer
Brief 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.
Detailed description
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
Interventions
DRUGTiragolumab
600mg every 3 weeks (Q3W)
DRUGAtezolizumab
1200mg every 3 weeks (Q3W)
DRUGIpilimumab
1 mg/kg, maximum of 4 cycles
Sponsors
Hoffmann-La Roche
The Netherlands Cancer Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PFS-12 | Assessed at 12 weeks | Progression-free survival rate as measured by the proportion of patients free of progression after 12-weeks of treatment |
| Incidence of adverse events | Assessed until 90 days after the last dose of study treatment or until initiation of new anti-cancer therapy, whichever occurs first | Number of patients with adverse events as measured according to CTCAE v5.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate | Assessed at week 6, week 12 and every 12 weeks thereafter; assessed up to 120 months | Complete response or partial response according to Response Evaluation Criteria in Solid Tumours in cancer immunotherapy trials (iRECIST) and Response Evaluation Criteria in Solid Tumours (RECIST version 1.1) |
| Clinical benefit rate | Assessed at week 6, week 12 and every 12 weeks thereafter; assessed up to 120 months | Complete response, partial response or stable disease for at least 24 weeks according to iRECIST and RECIST1.1 |
| Progression-free survival | Assessed at week 6, week 12 and every 12 weeks thereafter; median 12 months | Time from randomization to data of first tumor progression |
| Overall survival | Assessed monthly until date of death; median 12 months | Time from therapy initiation to death from any cause |
Countries
Netherlands
Contacts
Primary ContactMarleen Kok, MD
Backup ContactManon de Graaf, MD
Outcome results
None listed