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Recruiting NCT06342037

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

Phase II Interventional Metastatic Breast Cancer

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Tiragolumab, Atezolizumab, Ipilimumab.
Who it may be relevant to
Registry conditions: Metastatic Breast Cancer. Basic parameters: from 18 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
Netherlands
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Overview

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

  • Drug Tiragolumab
    600mg every 3 weeks (Q3W)
  • Drug Atezolizumab
    1200mg every 3 weeks (Q3W)
  • Drug Ipilimumab
    1 mg/kg, maximum of 4 cycles

Primary outcome measures

  • PFS-12 [Time frame: Assessed at 12 weeks]
  • Incidence of adverse events [Time frame: Assessed until 90 days after the last dose of study treatment or until initiation of new anti-cancer therapy, whichever occurs first]
Secondary outcome measures (4)
  • Objective response rate [Time frame: Assessed at week 6, week 12 and every 12 weeks thereafter; assessed up to 120 months]
  • Clinical benefit rate [Time frame: Assessed at week 6, week 12 and every 12 weeks thereafter; assessed up to 120 months]
  • Progression-free survival [Time frame: Assessed at week 6, week 12 and every 12 weeks thereafter; median 12 months]
  • Overall survival [Time frame: Assessed monthly until date of death; median 12 months]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Randomized
Model
Parallel assignment
Masking
Open label
Primary purpose
Treatment

Study locations

Netherlands · 1 center
  • Antoni van Leeuwenhoek — Amsterdam

Identifiers

NCT: NCT06342037 · N22TON

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗