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

NCT06342037 | Recruiting Phase 2

• 1 other identifier: N22TON
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Metastatic Breast Cancer

Keywords

Triple negative breast cancer

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (4)

• Objective response rate

  Assessed at week 6, week 12 and every 12 weeks thereafter; assessed up to 120 months

• Clinical benefit rate

  Assessed at week 6, week 12 and every 12 weeks thereafter; assessed up to 120 months

• Progression-free survival

  Assessed at week 6, week 12 and every 12 weeks thereafter; median 12 months

• Overall survival

  Assessed monthly until date of death; median 12 months

Study Arms (3)

Tiragolumab and atezolizumab

EXPERIMENTAL

Tiragolumab 600mg and atezolizumab 1200 mg, both every three weeks

Drug: Tiragolumab; Drug: Atezolizumab

Tiragolumab and ipilimumab

EXPERIMENTAL

Tiragolumab 600mg every 3 weeks and ipilimumab 1mg/kg every 3 weeks for the first 4 cycles

Drug: Tiragolumab; Drug: Ipilimumab

Tiragolumab, atezolizumab and ipilimumab

EXPERIMENTAL

Tiragolumab 600mg and atezolizumab 1200mg both every 3 weeks, plus ipilimumab 1mg/kg every 3 weeks for the first 4 cycles

Drug: Tiragolumab; Drug: Atezolizumab; Drug: Ipilimumab

Interventions

Tiragolumab DRUG

600mg every 3 weeks (Q3W)

Tiragolumab and atezolizumab; Tiragolumab and ipilimumab; Tiragolumab, atezolizumab and ipilimumab

Atezolizumab DRUG

1200mg every 3 weeks (Q3W)

Also known as: Tecentriq

Tiragolumab and atezolizumab; Tiragolumab, atezolizumab and ipilimumab

Ipilimumab DRUG

1 mg/kg, maximum of 4 cycles

Also known as: Yervoy

Tiragolumab and ipilimumab; Tiragolumab, atezolizumab and ipilimumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• The Netherlands Cancer Institute: lead
• Hoffmann-La Roche: collaborator

Study Sites (1)

Antoni van Leeuwenhoek

Amsterdam, North Holland, 1066CX, Netherlands

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

Tiragolumab; atezolizumab; Ipilimumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Marleen Kok, MD

  Antoni van Leeuwenhoek

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marleen Kok, MD

CONTACT

+31205129111; m.kok@nki.nl

Manon de Graaf, MD

CONTACT

+31205129111

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 7, 2024
• First Posted: April 2, 2024
• Study Start: June 12, 2024
• Primary Completion: April 1, 2026
• Study Completion (Estimated): April 1, 2030
• Last Updated: September 19, 2024

Record last verified: 2024-04

Locations

NL (1)