NOvel Immunotherapy Strategies for Advanced Triple Negative Breast Cancer (TNBC) Patients: TONIC-3 Trial

Trial Title: NOvel Immunotherapy Strategies for Advanced Triple Negative Breast Cancer (TNBC) Patients: TONIC-3 Trial

NCT ID: NCT06342037

Condition: Metastatic Breast Cancer

Conditions: Official terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Ipilimumab
Atezolizumab

Conditions: Keywords:
Triple negative breast cancer

Study type: Interventional

Study phase: Phase 2

Overall status: Recruiting

Study design:

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Tiragolumab
Description: 600mg every 3 weeks (Q3W)
Arm group label: Tiragolumab and atezolizumab
Arm group label: Tiragolumab and ipilimumab
Arm group label: Tiragolumab, atezolizumab and ipilimumab

Intervention type: Drug
Intervention name: Atezolizumab
Description: 1200mg every 3 weeks (Q3W)
Arm group label: Tiragolumab and atezolizumab
Arm group label: Tiragolumab, atezolizumab and ipilimumab

Other name: Tecentriq

Intervention type: Drug
Intervention name: Ipilimumab
Description: 1 mg/kg, maximum of 4 cycles
Arm group label: Tiragolumab and ipilimumab
Arm group label: Tiragolumab, atezolizumab and ipilimumab

Other name: Yervoy

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

Criteria for 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.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Antoni van Leeuwenhoek

Address:
City: Amsterdam
Zip: 1066CX
Country: Netherlands

Status: Recruiting

Contact:
Last name: Marleen Kok, MD

Phone: +31205129111
Email: m.kok@nki.nl

Contact backup:
Last name: Manon de Graaf, MD

Start date: June 12, 2024

Completion date: April 1, 2030

Lead sponsor:
Agency: The Netherlands Cancer Institute
Agency class: Other

Collaborator:
Agency: Hoffmann-La Roche
Agency class: Industry

Source: The Netherlands Cancer Institute

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06342037