Breast Cancer Early Stage Breast Cancer (Stage 1-3)ONSETNCT07597642
ON-treatment Single-cell Analysis for the Identification of Early Tumor Response Biomarkers on Prospective Collected Serial Tumor Biopsies in Triple Negative Breast Cancer Patient During Standard Neoadjuvant Chemo-immunotherapy
A study testing on treatment biopsy (after C1) in people with Breast Cancer Early Stage Breast Cancer (Stage 1-3), run by IRCCS San Raffaele at 1 site in Italy.
Trial summary
This study explores early breast cancer, focusing on triple-negative and high-risk luminal subtypes. It combines single-cell RNA sequencing and spatial imaging of tumor samples collected at different time points during treatment. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer Early Stage Breast Cancer (Stage 1-3)
- What is being tested?
- on treatment biopsy (after C1)
- Type of treatment
- Surgery or procedure
- How many people
- 55 participants
- Where
- 1 siteItaly
- Study dates
- Sep 2026to Mar 2029
- Phase
- Interventional
- 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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female patients aged ≥18 years.
- ECOG performance status 0-1.
- Histologically confirmed early breast cancer with one of the following molecular profiles:
- TNBC: ER and PR negative (IHC <10%) and HER2 negative (IHC 0-1+ or FISH non-amplified).
- High-risk luminal (ER+/HER2-): ER positive (IHC ≥10%) HER2 negative (IHC 0-1+ or FISH non-amplified), with high-risk features (e.g., Grade 3, PR-negative, high proliferation, high TILS).
- Clinical indication for neoadjuvant treatment according to standard practice:
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- TNBC: cT1c and/or cN positive, or cT2 (>2 cm) and/or cN positive (stage II,III).
- High-risk luminal: features as defined above (Grade 3, PR-negative, high proliferation, ER low).
- Ability to understand and sign written informed consent for participation in the study, approved by the local Ethics Committee.
Who cannot join
- HER2-positive tumors.
- Multifocal tumors - exclusion if a single index lesion cannot be identified and sampled; otherwise allowed if a representative lesion can be biopsied.
- Known metastatic disease. 4 Clinical contraindications to the planned neoadjuvant therapy.
- 5. Decision for upfront surgery as determined by the multidisciplinary team. 6. Inability to provide informed consent. 7. Pregnancy or breastfeeding. 8. Prior systemic therapy (chemotherapy, immunotherapy, or endocrine therapy) for the current breast cancer before baseline biopsy 9. On-treatment biopsy clinically not feasible or controindicated
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site
IRCCS Ospedale San Raffaele
Milan, Lombardy, 20132
Giulia Viale, MD, +390226437627, callcenter.mammella@hsronline.it
About this study
This study explores early breast cancer, focusing on triple-negative and high-risk luminal subtypes. It combines single-cell RNA sequencing and spatial imaging of tumor samples collected at different time points during treatment. The aim is to better understand how cancer cells and immune cells interact and to identify biomarkers that can predict whether a patient will respond to chemo-immunotherapy or develop resistance.
The study assumes that early molecular and spatial changes at the single-cell level can predict treatment response. This knowledge could help doctors adapt therapies, avoiding unnecessary treatment while improving effectiveness. The project seeks to reveal, for the first time, how cellular diversity and spatial relationships contribute to treatment resistance and disease progression.
Tumor samples will be analyzed before treatment, after the first treatment cycle (C1D1), and at surgery. Only the biopsy taken after C1D1 is collected specifically for this study; all other samples come from routine clinical care.
Read the detailed description
This exploratory translational study investigates early breast cancer (EBC), focusing on triple-negative (TNBC) and high-risk luminal (ER+/HER2-) subtypes. By integrating single-cell RNA sequencing, using the 10x Genomics platform (or similar technologies if it will be not available at the time of experiment), and spatial imaging analyses from serial tumor biopsies, the project aims to characterize tumor-immune interactions and identify predictive biomarkers of response or resistance to neoadjuvant chemo-immunotherapy.
We hypothesize that early molecular and spatial features, when detected at the single-cell level, can predict treatment sensitivity or resistance. This would enable adaptive therapeutic strategies that minimize overtreatment while maximizing efficacy in EBC. Our goal is to reveal, for the first time, the cellular heterogeneity and spatial interactions that drive therapy resistance and disease progression.
The analysis will be performed on tumor biopsies collected before the start of treatment, after C1D1 and on surgical material. The only tissue sample collected specifically for the study is the biopsy after C1D1.
- Being tested
- on treatment biopsy (after C1)
- Keywords
- triple negative breast cancer, high-risk luminal (ER+/HER2neg)
- Medical subject headings
- Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
on treatment biopsy (after C1)Procedure or surgery
Serial tumor tissue collection and analysis for the identification of early tumor response biomarkers. Tumor samples will be obtained at three predefined time points: (i) prior to initiation of treatment (baseline biopsy), (ii) after Cycle 1 Day 1 (C1D1) of therapy, and (iii) at the time of surgery (surgical specimen)
What is being measured
The primary outcome is the main question the study is designed to answer.
To characterize the dynamic changes in tumor and immune cell populations in TNBC and to prospectively collect serial samples from high-risk luminal (ER+/HER2-) breast cancer patients.
Gene expression levels per single-cell and relative cell clustering (%) by comparing pre-treatment, on-treatment (after first cycle of standard of care neoadiuvant therapy), and post-treatment (surgery or residual disease)
Measured: Pre-treatment, on-treatment (after first cycle of therapy), and post-treatment (surgery or residual disease)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2026
- Study startSep 2026 (estimated)
- Primary completionSep 2028 (estimated)
- Study completionMar 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast Cancer Early Stage Breast Cancer (Stage 1-3)Studies of the same condition, open and under way.
- More trials run by IRCCS San RaffaeleThe 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 N/A
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- the intervention is about the on treatment biopsy that is not required for standard of care
- Masking
- None (open label)
- Enrolment
- 55 participants (estimated)
Sponsor and investigators
- Lead sponsor
- IRCCS San Raffaele
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Giulia Viale, IRCCS San Raffaele
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07597642
- Sponsor's protocol ID
- ONSET
- Acronym
- ONSET
- Status last verified
- May 2026
- First submitted
- 8 May 2026
- Last updated
- 22 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ON-treatment Single-cell Analysis for the Identification of Early Tumor Response Biomarkers on Prospective Collected Serial Tumor Biopsies in Triple Negative Breast Cancer Patient During Standard Neoadjuvant Chemo-immunotherapy
- ClinicalTrials.gov ID
- NCT07597642
- Acronym / sponsor ID
- ONSET / ONSET
- Keywords
- triple negative breast cancer, high-risk luminal (ER+/HER2neg)
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 55 participants (estimated)
- Lead sponsor
- IRCCS San RaffaeleUniversity, hospital or other
- Study start
- Sep 2026 (estimated)
- Primary completion
- Sep 2028 (estimated)
- Study completion
- Mar 2029 (estimated)
- First posted
- 19 May 2026 (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 study explores early breast cancer, focusing on triple-negative and high-risk luminal subtypes. It combines single-cell RNA sequencing and spatial imaging of tumor samples collected at different time points during treatment. The aim is to better understand how cancer cells and immune cells interact and to identify biomarkers that can predict whether a patient will respond to chemo-immunotherapy or develop resistance.
The study assumes that early molecular and spatial changes at the single-cell level can predict treatment response. This knowledge could help doctors adapt therapies, avoiding unnecessary treatment while improving effectiveness. The project seeks to reveal, for the first time, how cellular diversity and spatial relationships contribute to treatment resistance and disease progression.
Tumor samples will be analyzed before treatment, after the first treatment cycle (C1D1), and at surgery. Only the biopsy taken after C1D1 is collected specifically for this study; all other samples come from routine clinical care.
Detailed description
This exploratory translational study investigates early breast cancer (EBC), focusing on triple-negative (TNBC) and high-risk luminal (ER+/HER2-) subtypes. By integrating single-cell RNA sequencing, using the 10x Genomics platform (or similar technologies if it will be not available at the time of experiment), and spatial imaging analyses from serial tumor biopsies, the project aims to characterize tumor-immune interactions and identify predictive biomarkers of response or resistance to neoadjuvant chemo-immunotherapy.
We hypothesize that early molecular and spatial features, when detected at the single-cell level, can predict treatment sensitivity or resistance. This would enable adaptive therapeutic strategies that minimize overtreatment while maximizing efficacy in EBC. Our goal is to reveal, for the first time, the cellular heterogeneity and spatial interactions that drive therapy resistance and disease progression.
The analysis will be performed on tumor biopsies collected before the start of treatment, after C1D1 and on surgical material. The only tissue sample collected specifically for the study is the biopsy after C1D1.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Model description
- the intervention is about the on treatment biopsy that is not required for standard of care
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Female patients aged ≥18 years.
- ECOG performance status 0-1.
- Histologically confirmed early breast cancer with one of the following molecular profiles:
- Clinical indication for neoadjuvant treatment according to standard practice:
- Ability to understand and sign written informed consent for participation in the study, approved by the local Ethics Committee.
Key exclusion criteria (4 listed)
- HER2-positive tumors.
- Multifocal tumors - exclusion if a single index lesion cannot be identified and sampled; otherwise allowed if a representative lesion can be biopsied.
- Known metastatic disease. 4 Clinical contraindications to the planned neoadjuvant therapy.
- 5. Decision for upfront surgery as determined by the multidisciplinary team. 6. Inability to provide informed consent. 7. Pregnancy or breastfeeding. 8. Prior systemic therapy (chemotherapy, immunotherapy, or endocrine therapy) for the current breast cancer before baseline biopsy 9. On-treatment biopsy clinically not feasible or controindicated
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 |
|---|---|---|
| on treatment biopsy (after C1)Serial tumor tissue collection and analysis for the identification of early tumor response biomarkers. Tumor samples will be obtained at three predefined time points: (i) prior to initiation of treatment (baseline biopsy), (ii) after Cycle 1 Day 1 (C1D1) of therapy, and (iii) at the time of surgery (surgical specimen) | Procedure or surgery | – |
Primary outcome
To characterize the dynamic changes in tumor and immune cell populations in TNBC and to prospectively collect serial samples from high-risk luminal (ER+/HER2-) breast cancer patients.
Time frame: Pre-treatment, on-treatment (after first cycle of therapy), and post-treatment (surgery or residual disease)
Gene expression levels per single-cell and relative cell clustering (%) by comparing pre-treatment, on-treatment (after first cycle of standard of care neoadiuvant therapy), and post-treatment (surgery or residual disease)
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 22 May 2026.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing on treatment biopsy (after C1) in people with Breast Cancer Early Stage Breast Cancer (Stage 1-3), run by IRCCS San Raffaele at 1 site in Italy.
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 4 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: opening soon, as of the sponsor's last update on 22 May 2026. 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 Italy. 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.
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 Giulia Viale, MD (+390226437627, callcenter.mammella@hsronline.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To characterize the dynamic changes in tumor and immune cell populations in TNBC and to prospectively collect serial samples from high-risk luminal (ER+/HER2-) breast cancer patients. (time frame: Pre-treatment, on-treatment (after first cycle of therapy), and post-treatment (surgery or residual disease)). 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 22 May 2026.