Metastatic Breast CancerPhase 2TONIC-3NCT06342037
NOvel Immunotherapy Strategies for Advanced Triple Negative Breast Cancer (TNBC) Patients: TONIC-3 Trial
A Phase 2 study testing Tiragolumab, Atezolizumab and Ipilimumab in people with Metastatic Breast Cancer, run by The Netherlands Cancer Institute at 1 site in Netherlands.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Breast Cancer
- What is being tested?
- Tiragolumab, Atezolizumab and Ipilimumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteNetherlands
- Study dates
- 12 Jun 2024to 1 Apr 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Manon de Graaf, MD contact
Netherlands1 site, 1 recruiting
- Recruiting
Antoni van Leeuwenhoek
Amsterdam, North Holland, 1066CX
Marleen Kok, MD, +31205129111, m.kok@nki.nl
Manon de Graaf, MD
About this study
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.
Read the 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
- Conditions
- Metastatic Breast Cancer
- Being tested
- Tiragolumab, Atezolizumab, Ipilimumab
- Keywords
- Triple negative breast cancer
- Medical subject headings
- Breast Neoplasms, Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TiragolumabDrug
600mg every 3 weeks (Q3W)
AtezolizumabDrug
Also called Tecentriq
1200mg every 3 weeks (Q3W)
IpilimumabDrug
Also called Yervoy
1 mg/kg, maximum of 4 cycles
| Study group | Role | What they receive |
|---|---|---|
| Tiragolumab and atezolizumab | Experimental | Tiragolumab 600mg and atezolizumab 1200 mg, both every three weeks Receives: 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 Receives: 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 Receives: Drug: Tiragolumab; Drug: Atezolizumab; Drug: Ipilimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
PFS-12
Progression-free survival rate as measured by the proportion of patients free of progression after 12-weeks of treatment
Measured: Assessed at 12 weeks
Incidence of adverse events
Number of patients with adverse events as measured according to CTCAE v5.0
Measured: 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
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)
Measured: Assessed at week 6, week 12 and every 12 weeks thereafter; assessed up to 120 months
Clinical benefit rate
Complete response, partial response or stable disease for at least 24 weeks according to iRECIST and RECIST1.1
Measured: Assessed at week 6, week 12 and every 12 weeks thereafter; assessed up to 120 months
Progression-free survival
Time from randomization to data of first tumor progression
Measured: Assessed at week 6, week 12 and every 12 weeks thereafter; median 12 months
Overall survival
Time from therapy initiation to death from any cause
Measured: Assessed monthly until date of death; median 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2024
- Study start12 Jun 2024
- Primary completion1 Apr 2026 (estimated)
- Study completion1 Apr 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Breast CancerStudies of the same condition, open and under way.
- More trials run by The Netherlands Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Netherlands Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Hoffmann-La Roche
- Responsible party
- Sponsor
- Investigators
- Marleen Kok, MD, Principal investigator, Antoni van Leeuwenhoek
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06342037
- Sponsor's protocol ID
- N22TON
- Acronym
- TONIC-3
- Status last verified
- Apr 2024
- First submitted
- 7 Mar 2024
- Last updated
- 19 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- NOvel Immunotherapy Strategies for Advanced Triple Negative Breast Cancer (TNBC) Patients: TONIC-3 Trial
- ClinicalTrials.gov ID
- NCT06342037
- Acronym / sponsor ID
- TONIC-3 / N22TON
- Conditions
- Metastatic Breast Cancer
- Keywords
- Triple negative breast cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- The Netherlands Cancer InstituteUniversity, hospital or other
- Collaborators
- Hoffmann-La Roche
- Study start
- 12 Jun 2024 (actual)
- Primary completion
- 1 Apr 2026 (estimated)
- Study completion
- 1 Apr 2030 (estimated)
- First posted
- 2 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Tiragolumab and atezolizumab | Experimental | Drug: Tiragolumab, Drug: AtezolizumabTiragolumab 600mg and atezolizumab 1200 mg, both every three weeks |
| Tiragolumab and ipilimumab | Experimental | Drug: Tiragolumab, Drug: IpilimumabTiragolumab 600mg every 3 weeks and ipilimumab 1mg/kg every 3 weeks for the first 4 cycles |
| Tiragolumab, atezolizumab and ipilimumab | Experimental | Drug: Tiragolumab, Drug: Atezolizumab, Drug: IpilimumabTiragolumab 600mg and atezolizumab 1200mg both every 3 weeks, plus ipilimumab 1mg/kg every 3 weeks for the first 4 cycles |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tiragolumab600mg every 3 weeks (Q3W) | Drug | Tiragolumab and atezolizumab, Tiragolumab and ipilimumab, Tiragolumab, atezolizumab and ipilimumab |
| AtezolizumabAlso: Tecentriq1200mg every 3 weeks (Q3W) | Drug | Tiragolumab and atezolizumab, Tiragolumab, atezolizumab and ipilimumab |
| IpilimumabAlso: Yervoy1 mg/kg, maximum of 4 cycles | Drug | Tiragolumab and ipilimumab, Tiragolumab, atezolizumab and ipilimumab |
Primary outcome
PFS-12
Time frame: 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
Time frame: 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
4 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Manon de Graaf, MD contact
Marleen Kok, MD principal investigator
Antoni van Leeuwenhoek
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tiragolumab, Atezolizumab and Ipilimumab in people with Metastatic Breast Cancer, run by The Netherlands Cancer Institute at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Marleen Kok, MD (+31205129111, m.kok@nki.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PFS-12 (time frame: Assessed at 12 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.