Breast CancerNCT07582887
Impact of Genetic Variants on the Toxicity of Antibody-Drug Conjugates in Locally Advanced or Metastatic Breast Cancer: The Role of the UGT1A1 Gene as a Predictive Biomarker of Therapeutic Response
An observational study of Breast Cancer and Metastatic Breast Cancer, run by Fundación Pública Andaluza para la Investigación Biomédica Andalucía Oriental at 1 site in Spain.
Trial summary
The metabolism of anticancer drugs is influenced by genetic variants that affect their bioavailability and toxicity. In the case of antibody-drug conjugates (ADCs), such as sacituzumab-govitecan (SG), trastuzumab-deruxtecan (T-DXd), and datopotamab-deruxtecan (Dato-DXd), the enzyme UDP-glucuronosyltransferase 1A1… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer, Metastatic Breast Cancer, Drug-Related Side Effects and Adverse Reactions
- What is being tested?
- Sacituzumab Govitecan, Trastuzumab deruxtecan and Datopotamab Deruxtecan
- How many people
- 70 participants
- Where
- 1 siteSpain
- Study dates
- 15 Jul 2025to 31 Mar 2027
- How long will I take part?
- 2 Years
- Phase
- Observational
- 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
Study population: Patients with early, locally advanced, or metastatic breast cancer treated with antibody-drug conjugates in a real-world clinical setting at a single tertiary hospital.
Who may be able to join
- Patients aged 18 years or older.
- Patients diagnosed with breast cancer starting or undergoing treatment with Sacituzumab Govitecan, Trastuzumab Deruxtecan, or Datopotamab Deruxtecan.
- Provision of signed informed consent for the genetic study.
Who cannot join
- Patients who are ultimately not treated with the specified Antibody-Drug Conjugates.
- Refusal to provide informed consent for genetic analysis.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Isabel Blancas López-Barajas, MD, PhD contact
Spain1 site, 1 recruiting
- Recruiting
Hospital Universitario Clínico San Cecilio
Granada, Granada, 18016
Isabel Blancas López-Barajas, MD, PhD, +34 958 023265, ensayosclinicosom.husc.sspa@juntadeandalucia.es
Isabel Blancas López-Barajas, MD, PhD
About this study
The metabolism of anticancer drugs is influenced by genetic variants that affect their bioavailability and toxicity. In the case of antibody-drug conjugates (ADCs), such as sacituzumab-govitecan (SG), trastuzumab-deruxtecan (T-DXd), and datopotamab-deruxtecan (Dato-DXd), the enzyme UDP-glucuronosyltransferase 1A1 (UGT1A1) plays a central role in the glucuronidation and elimination of their cytotoxic components. In particular, the metabolism of SN-38, the active metabolite of irinotecan and SG, is highly influenced by variants in UGT1A1, leading to drug accumulation and the development of severe toxicities. Patients with variants such as UGT1A1*28 (rs3064744) and UGT1A1*6 (rs4148323) exhibit reduced enzyme activity, increasing the risk of neutropenia and severe diarrhea.
The relevance of UGT1A1 is not limited to sacituzumab-govitecan; its role in the elimination of camptothecin derivatives suggests it could also impact the toxicity of trastuzumab-deruxtecan and datopotamab-deruxtecan, which contain deruxtecan, a cytotoxic agent 10 times more potent than irinotecan. Despite strong evidence linking the UGT1A1 genotype to irinotecan toxicity, there are currently no established pharmacogenetic recommendations for antidiuretic peptides (ADCs) in metastatic breast cancer.
- Conditions
- Breast Cancer, Metastatic Breast Cancer, Drug-Related Side Effects and Adverse Reactions, Pharmacogenetic Variant
- Being tested
- Sacituzumab Govitecan, Trastuzumab deruxtecan, Datopotamab Deruxtecan
- Keywords
- UGT1A1, Genetic Variants, Toxicity, polymorphism, Breast Cancer, Sacituzumab Govitecan, Trastuzumab Deruxtecan, Datopotamab Deruxtecan
- Medical subject headings
- Breast Neoplasms, Drug-Related Side Effects and Adverse Reactions
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sacituzumab GovitecanDrug
Administered according to standard clinical practice and product label.
Trastuzumab deruxtecanDrug
Administered according to standard clinical practice and product label.
Datopotamab DeruxtecanDrug
Administered according to standard clinical practice and product label.
| Study group | Role | What they receive |
|---|---|---|
| Patients undergoing treatment with sacituzumab govitecan | Standard clinical dose of sacituzumab govitecan administered as per routine clinical practice. Receives: Drug: Sacituzumab Govitecan | |
| Patients undergoing treatment with trastuzumab-deruxtecan | Standard clinical dose of trastuzumab-deruxtecan administered as per routine clinical practice. Receives: Drug: Trastuzumab deruxtecan | |
| Patients undergoing treatment with datopotamab deruxtecan | Standard clinical dose of datopotamab deruxtecan administered as per routine clinical practice. Receives: Drug: Datopotamab Deruxtecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Severe Drug-Related Toxicities (Grade ≥ 3)
Number of patients experiencing severe hematological or gastrointestinal toxicities (defined as Grade 3 or higher according to CTCAE v5.0) that are definitely, probably, or possibly related to the treatment with Sacituzumab Govitecan, Trastuzumab Deruxtecan, or Datopotamab Deruxtecan.
Measured: From the start of treatment until the end of the follow-up period (up to 2 years).
Secondary outcomes (3)
Frequency of UGT1A1*28 Allele
Distribution and allelic frequency of the UGT1A1*28 variant in the study population of breast cancer patients.
Measured: At baseline (once the genetic study is performed).
Correlation Between Genetic Variants and Toxicity Severity
Statistical association (using Odds Ratio) between the identified genetic variants (rs4148323, rs35350906, rs3064744, rs887829, rs111741722) and the severity of adverse events.
Measured: Analyzed at the completion of the 2-year study period.
Predictive Model for Severe Toxicity
Design of a predictive model based on genetic markers to anticipate the appearance of severe toxicities for each ADC studied.
Measured: At the end of the study (2 years).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2026
- Study start15 Jul 2025
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Other
- Enrolment
- 70 participants (estimated)
- Target duration
- 2 Years
Sponsor and investigators
- Lead sponsor
- Fundación Pública Andaluza para la Investigación Biomédica Andalucía Oriental
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Isabel Blancas López Barajas, Fundación Pública Andaluza para la Investigación Biomédica Andalucía Oriental
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07582887
- Sponsor's protocol ID
- FIB-MAM-2025-04
- Status last verified
- May 2026
- First submitted
- 6 May 2026
- Last updated
- 13 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data will not be shared to ensure patient confidentiality and compliance with data protection regulations. Aggregate results will be available through scientific publications.
Publications
Trita AS, Biafora A, Pichette Drapeau M, Weber P, Goossen LJ. Regiospecific ortho-C-H Allylation of Benzoic Acids. Angew Chem Int Ed Engl. 2018 Oct 26;57(44):14580-14584. doi: 10.1002/anie.201712520. Epub 2018 Mar 5.
PubMed 29411933Sony M, Antony J, McDermott O. The Impact of Healthcare 4.0 on the Healthcare Service Quality: A Systematic Literature Review. Hosp Top. 2023;101(4):288-304. doi: 10.1080/00185868.2022.2048220. Epub 2022 Mar 24.
PubMed 35324390Bardia A, Hurvitz SA, Tolaney SM, Loirat D, Punie K, Oliveira M, Brufsky A, Sardesai SD, Kalinsky K, Zelnak AB, Weaver R, Traina T, Dalenc F, Aftimos P, Lynce F, Diab S, Cortes J, O'Shaughnessy J, Dieras V, Ferrario C, Schmid P, Carey LA, Gianni L, Piccart MJ, Loibl S, Goldenberg DM, Hong Q, Olivo MS, Itri LM, Rugo HS; ASCENT Clinical Trial Investigators. Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer. N Engl J Med. 2021 Apr 22;384(16):1529-1541. doi: 10.1056/NEJMoa2028485.
PubMed 33882206
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Genetic Variants on the Toxicity of Antibody-Drug Conjugates in Locally Advanced or Metastatic Breast Cancer: The Role of the UGT1A1 Gene as a Predictive Biomarker of Therapeutic Response
- ClinicalTrials.gov ID
- NCT07582887
- Acronym / sponsor ID
- FIB-MAM-2025-04
- Conditions
- Breast Cancer, Metastatic Breast Cancer, Drug-Related Side Effects and Adverse Reactions, Pharmacogenetic Variant
- Keywords
- UGT1A1, Genetic Variants, Toxicity, polymorphism, Breast Cancer, Sacituzumab Govitecan, Trastuzumab Deruxtecan, Datopotamab Deruxtecan
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- Fundación Pública Andaluza para la Investigación Biomédica Andalucía OrientalUniversity, hospital or other
- Study start
- 15 Jul 2025 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Mar 2027 (estimated)
- First posted
- 13 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.
The metabolism of anticancer drugs is influenced by genetic variants that affect their bioavailability and toxicity. In the case of antibody-drug conjugates (ADCs), such as sacituzumab-govitecan (SG), trastuzumab-deruxtecan (T-DXd), and datopotamab-deruxtecan (Dato-DXd), the enzyme UDP-glucuronosyltransferase 1A1 (UGT1A1) plays a central role in the glucuronidation and elimination of their cytotoxic components. In particular, the metabolism of SN-38, the active metabolite of irinotecan and SG, is highly influenced by variants in UGT1A1, leading to drug accumulation and the development of severe toxicities. Patients with variants such as UGT1A1*28 (rs3064744) and UGT1A1*6 (rs4148323) exhibit reduced enzyme activity, increasing the risk of neutropenia and severe diarrhea.
The relevance of UGT1A1 is not limited to sacituzumab-govitecan; its role in the elimination of camptothecin derivatives suggests it could also impact the toxicity of trastuzumab-deruxtecan and datopotamab-deruxtecan, which contain deruxtecan, a cytotoxic agent 10 times more potent than irinotecan. Despite strong evidence linking the UGT1A1 genotype to irinotecan toxicity, there are currently no established pharmacogenetic recommendations for antidiuretic peptides (ADCs) in metastatic breast cancer.
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Target follow-up
- 2 Years
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Patients undergoing treatment with sacituzumab govitecan | – | Drug: Sacituzumab GovitecanStandard clinical dose of sacituzumab govitecan administered as per routine clinical practice. |
| Patients undergoing treatment with trastuzumab-deruxtecan | – | Drug: Trastuzumab deruxtecanStandard clinical dose of trastuzumab-deruxtecan administered as per routine clinical practice. |
| Patients undergoing treatment with datopotamab deruxtecan | – | Drug: Datopotamab DeruxtecanStandard clinical dose of datopotamab deruxtecan administered as per routine clinical practice. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with early, locally advanced, or metastatic breast cancer treated with antibody-drug conjugates in a real-world clinical setting at a single tertiary hospital.
Key inclusion criteria (3 listed)
- Patients aged 18 years or older.
- Patients diagnosed with breast cancer starting or undergoing treatment with Sacituzumab Govitecan, Trastuzumab Deruxtecan, or Datopotamab Deruxtecan.
- Provision of signed informed consent for the genetic study.
Key exclusion criteria (2 listed)
- Patients who are ultimately not treated with the specified Antibody-Drug Conjugates.
- Refusal to provide informed consent for genetic analysis.
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 |
|---|---|---|
| Sacituzumab GovitecanAdministered according to standard clinical practice and product label. | Drug | Patients undergoing treatment with sacituzumab govitecan |
| Trastuzumab deruxtecanAdministered according to standard clinical practice and product label. | Drug | Patients undergoing treatment with trastuzumab-deruxtecan |
| Datopotamab DeruxtecanAdministered according to standard clinical practice and product label. | Drug | Patients undergoing treatment with datopotamab deruxtecan |
Primary outcome
Incidence of Severe Drug-Related Toxicities (Grade ≥ 3)
Time frame: From the start of treatment until the end of the follow-up period (up to 2 years).
Number of patients experiencing severe hematological or gastrointestinal toxicities (defined as Grade 3 or higher according to CTCAE v5.0) that are definitely, probably, or possibly related to the treatment with Sacituzumab Govitecan, Trastuzumab Deruxtecan, or Datopotamab Deruxtecan.
3 secondary outcomes
Frequency of UGT1A1*28 Allele
Time frame: At baseline (once the genetic study is performed).
Correlation Between Genetic Variants and Toxicity Severity
Time frame: Analyzed at the completion of the 2-year study period.
Predictive Model for Severe Toxicity
Time frame: At the end of the study (2 years).
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 13 May 2026.
- Results publication: PubMed 29411933Trita AS, Biafora A, Pichette Drapeau M, Weber P, Goossen LJ. Regiospecific ortho-C-H Allylation of Benzoic Acids. Angew Chem Int Ed Engl. 2018 Oct 26;57(44):14580-14584. doi: 10.1002/anie.201712520. Epub 2018 Mar 5.
- Results publication: PubMed 35324390Sony M, Antony J, McDermott O. The Impact of Healthcare 4.0 on the Healthcare Service Quality: A Systematic Literature Review. Hosp Top. 2023;101(4):288-304. doi: 10.1080/00185868.2022.2048220. Epub 2022 Mar 24.
- Results publication: PubMed 33882206Bardia A, Hurvitz SA, Tolaney SM, Loirat D, Punie K, Oliveira M, Brufsky A, Sardesai SD, Kalinsky K, Zelnak AB, Weaver R, Traina T, Dalenc F, Aftimos P, Lynce F, Diab S, Cortes J, O'Shaughnessy J, Dieras V, Ferrario C, Schmid P, Carey LA, Gianni L, Piccart MJ, Loibl S, Goldenberg DM, Hong Q, Olivo MS, Itri LM, Rugo HS; ASCENT Clinical Trial Investigators. Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer. N Engl J Med. 2021 Apr 22;384(16):1529-1541. doi: 10.1056/NEJMoa2028485.
- FIBAO - Fundación para la Investigación Biosanitaria de Andalucía Oriental.Link provided by the sponsor.
- Individual participant dataSharing planned: No. Individual participant data will not be shared to ensure patient confidentiality and compliance with data protection regulations. Aggregate results will be available through scientific publications.
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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.
Isabel Blancas López-Barajas, MD, PhD contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Breast Cancer and Metastatic Breast Cancer, run by Fundación Pública Andaluza para la Investigación Biomédica Andalucía Oriental at 1 site in Spain.
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 3 inclusion and 2 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 13 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 Spain. 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 Isabel Blancas López-Barajas, MD, PhD (+34 958 023265, ensayosclinicosom.husc.sspa@juntadeandalucia.es), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Severe Drug-Related Toxicities (Grade ≥ 3) (time frame: From the start of treatment until the end of the follow-up period (up to 2 years).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07582887, which also lists 3 linked publications.
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 13 May 2026.