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

Metastatic Breast Cancer Clinical Trial

— TONIC-3  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06342037
• Other study ID #: N22TON
• Status: Recruiting
• Phase: Phase 2
• Start date: June 12, 2024
• Est. completion date: April 1, 2030

Study information

• Verified date: April 2024
• Source: The Netherlands Cancer Institute
• Contact: Marleen Kok, MD
• Phone: +3120512
• Email: m.kok[@]nki.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: April 1, 2030
• Est. primary completion date: April 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

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

Locations

Country	Name	City	State
Netherlands	Antoni van Leeuwenhoek	Amsterdam	Noord-Holland

Sponsors (2)

Lead Sponsor	Collaborator
The Netherlands Cancer Institute	Hoffmann-La Roche

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PFS-12	Progression-free survival rate as measured by the proportion of patients free of progression after 12-weeks of treatment	Assessed at 12 weeks
Primary	Incidence of adverse events	Number of patients with adverse events as measured according to CTCAE v5.0	Assessed until 90 days after the last dose of study treatment or until initiation of new anti-cancer therapy, whichever occurs first
Secondary	Objective response rate	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)	Assessed at week 6, week 12 and every 12 weeks thereafter; assessed up to 120 months
Secondary	Clinical benefit rate	Complete response, partial response or stable disease for at least 24 weeks according to iRECIST and RECIST1.1	Assessed at week 6, week 12 and every 12 weeks thereafter; assessed up to 120 months
Secondary	Progression-free survival	Time from randomization to data of first tumor progression	Assessed at week 6, week 12 and every 12 weeks thereafter; median 12 months
Secondary	Overall survival	Time from therapy initiation to death from any cause	Assessed monthly until date of death; median 12 months