Breast CancerPhase 2NCT07619365
Trastuzumab Deruxtecan and Lovastatin in HER2-low and Ultralow Advanced or Metastatic Breast Cancer
A Phase 2 study testing Trastuzumab deruxtecan and Lovastatin in people with Breast Cancer and Advanced Breast Cancer, run by Washington University School of Medicine at 1 site in United States.
Trial summary
The purpose of this study is to evaluate the use of lovastatin, a cholesterol-depleting pro-drug that may lower CAV-1 levels, in order to increase HER2 expression on the cell surface of cancer cells and enhance the uptake and efficacy of trastuzumab deruxtecan (T-DXd) in HER2-low and ultralow breast tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer, Advanced Breast Cancer, Metastatic Breast Cancer
- What is being tested?
- Trastuzumab deruxtecan and Lovastatin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Nov 2026to 30 Nov 2031
- 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
- Histologically or cytologically confirmed HER2 low (IHC 1+ or 2+ with negative in-situ hybridization) or ultralow (IHC 0 with incomplete/faint membrane staining in >0 but ≤10% of tumor cells) breast cancer based on the most recent biopsy. Patients may be advanced/unresectable or metastatic.
- Patients must have received no more than 1 prior line of chemotherapy (e.g. capecitabine). There is no limit on the prior number of endocrine-based therapies for patients with hormone-receptor positivity.
- Measurable disease per RECIST 1.1.
- At least 18 years of age.
- ECOG performance status ≤ 2
- Adequate bone marrow and organ function as defined below:
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- Absolute neutrophil count ≥ 1.5 K/cumm
- Platelets ≥ 100 K/cumm
- Hemoglobin ≥ 9.0 g/dL
- Total bilirubin ≤ 1.5 x IULN
- AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
- Creatinine clearance > 45 mL/min by Cockcroft-Gault
- The effects of T-DXd and lovastatin on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 7 months after the last dose of either study drug. Should a woman become pregnant or suspect she is pregnant while participating in this study or should a man suspect he has fathered a child, s/he must inform her treating physician immediately.
- Patients must have left ventricular ejection fraction (LVEF) of ≥50% by either an echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 days before C1D-1.
- Agreement to adhere to Lifestyle Considerations throughout study duration
- Ability to understand and willingness to sign an IRB approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.
Who cannot join
- Prior treatment with T-DXd or other topoisomerase I ADC including sacituzumab govitecan, datopotamab deruxtecan, or investigational ADCs with topoisomerase I payloads.
- Prior statin use within 7 days prior to C1D-1.
- Patients with unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to grade ≤1 or baseline. Participants with chronic grade 2 toxicities may be eligible per the discretion of the Investigator after consultation with the Study PI or designee (e.g., grade 2 chemotherapy-induced neuropathy).
- Prior or concurrent malignancy whose natural history has the potential to interfere with the safety or efficacy assessment of the investigational regimen. Patients with prior or concurrent malignancy that does NOT meet that definition are eligible for this trial
- Currently receiving any other investigational agents, or receipt of any investigational agents within 3 weeks or 5 half-lives, whichever is shorter, prior to C1D-1.
- Receipt of chemotherapy, immunotherapy, endocrine therapy, or other systemic anticancer therapy within 3 weeks or 5 half-lives, whichever is shorter, prior to C1D-1.
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- Patients with untreated brain metastases. Patients with treated brain metastases are allowed if post-treatment brain-imaging after CNS-directed therapy shows no evidence of progression, and patients are not taking steroids to control edema or other symptoms.
- A history of allergic reactions attributed to compounds of similar chemical or biologic composition to T-DXd, lovastatin, or other agents used in the study.
- Patients with clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (i.e. pulmonary emboli within three months of the study enrollment, severe asthma, severe COPD, restrictive lung disease, etc.), and any autoimmune, connective tissue or inflammatory disorders with potential pulmonary involvement (i.e. Rheumatoid arthritis, Sjogren's, sarcoidosis, etc.), or prior pneumonectomy.
- Patients with a history of non-infectious ILD/pneumonitis that required steroids or has current ILD/pneumonitis. Patients with a history of infectious ILD/pneumonitis should be discussed with the study PI.
- Prior intolerance to statin therapy, defined as intolerable muscle symptoms or significant transaminitis elevation (>3x ULN) or CK elevation (>5x ULN) attributed to statin therapy within the last 2 years prior to C1D-1.
- Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or clinically significant cardiac arrhythmia.
- History or current significant cardiovascular disease, stroke, severe dyslipidemia, or vascular disorders that require continuous statin dosing. Uncertain cases should be discussed with the study PI for clarification of eligibility.
- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative serum or urine pregnancy test within 14 days of C1D1.
- HIV-infected if not on effective anti-retroviral therapy with undetectable viral load for 6 months. Patients with HIV who are receiving effective anti-retroviral therapy and have had an undetectable viral load for at least 6 months are eligible. HIV testing not required in the absence of known history of infection.
- Evidence of chronic hepatitis B virus (HBV) that is detectable on suppressive therapy. Patients with evidence of chronic HBV infection with undetectable HBV viral load on suppressive therapy are eligible. HBV testing not required in the absence of known history of infection.
- History of hepatitis C virus (HCV) infection that has not been cured or that has a detectable viral load. Patients with a history of HCV that has been treated and cured are eligible. Patients with HCV infection who are currently on treatment and have an undetectable HCV viral load are eligible. HCV testing not required in the absence of known history of infection.
- Use of strong inhibitors of CYP3A4 within 5 half-lives of the medication prior to C1D-1.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
Andrew A Davis, MD, 314-362-5740, aadavis@wustl.edu
Andrew A Davis, MD
About this study
Official title: Phase II Trial Evaluating Trastuzumab Deruxtecan and Lovastatin in HER2-low and Ultralow Advanced or Metastatic Breast Cancer (MBC)
The purpose of this study is to evaluate the use of lovastatin, a cholesterol-depleting pro-drug that may lower CAV-1 levels, in order to increase HER2 expression on the cell surface of cancer cells and enhance the uptake and efficacy of trastuzumab deruxtecan (T-DXd) in HER2-low and ultralow breast tumors.
- Being tested
- Trastuzumab deruxtecan, Lovastatin
- Keywords
- Antibody drug conjugate, HER2 low, HER2 ultralow
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Trastuzumab deruxtecanDrug
Also called T-DXd, Enhertu
Standard of care trastuzumab deruxtecan is administered at a starting dose of 5.4 mg/kg intravenously every 3 weeks according to package guidelines. The first infusion is administered over 90 minutes, and subsequent infusions may be administered over 30 minutes if prior infusions were well tolerated.
LovastatinDrug
Also called Mevacor, Altoprev, Altocor
Lovastatin is provided in 10 mg and 20mg tablets for oral administration. It will be taken approximately 12 hours and 10 minutes before each T-DXd cycle.
| Study group | Role | What they receive |
|---|---|---|
| Safety Lead In: Trastuzumab Deruxtecan (T-DXd) + Lovastatin | Experimental | T-DXd will be administered at a standard dose intravenously (IV) every 21 days and lovastatin will be administered orally at 20 mg with doses approximately 12 hours and 30 minutes before each cycle of T-DXd. Patients will be assessed for unacceptable toxicities during the first two treatment cycles. Receives: Drug: Trastuzumab deruxtecan; Drug: Lovastatin |
| Standard dose: Trastuzumab Deruxtecan (T-DXd) + Lovastatin | Experimental | T-DXd will be administered at a standard dose intravenously (IV) every 21 days and lovastatin will be administered orally at 20 mg with doses approximately 12 hours and 30 minutes before each cycle of T-DXd. Receives: Drug: Trastuzumab deruxtecan; Drug: Lovastatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR)
ORR is defined as the proportion of patients who achieve complete response (CR) or partial response (PR) according to RECIST v1.1.
CR is defined as disappearance of all target lesions. Disappearance of all non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Measured: Start of treatment through end of treatment (estimated total time 12 months)
Secondary outcomes (4)
Progression Free Survival (PFS)
PFS is defined from treatment start date to date of progression or date of death due to any cause or date of last follow up, whichever is earlier. PFS will be analyzed by the Kaplan-Meier method.
Progressive disease (PD) is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).
Measured: Start of treatment to date of progression, death, or date of last follow up whichever is earlier (total estimated time to be 24 months)
Overall Survival (OS)
OS is defined from start of treatment to date of death due to any cause or last date of follow up. OS will be analyzed by the Kaplan-Meier method.
Measured: Start of treatment to date of progression, death, or date of last follow up (total estimated time to be 24 months)
Safety lead-in only: Rate of unacceptable toxicities
Unacceptable toxicities are assessed according to CTCAE v6.0 and specified in study protocol.
Measured: Start of treatment to completion of Cycle 2 (each cycle is 3 weeks in length, estimated total time 6 weeks)
Number and type of adverse events (AEs)
AEs assessed according to CTCAE v6.0.
Measured: Start of treatment through 30 days post last dose of either study treatment, whichever is later (estimated total time 13 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2026
- Study start30 Nov 2026 (estimated)
- Primary completion30 Nov 2030 (estimated)
- Study completion30 Nov 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe 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
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), The Foundation for Barnes-Jewish Hospital
- Responsible party
- Sponsor
- Investigators
- Andrew A Davis, MD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07619365
- Sponsor's protocol ID
- 202606082
- Status last verified
- Oct 2026
- First submitted
- 21 May 2026
- Last updated
- 2 Nov 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial Evaluating Trastuzumab Deruxtecan and Lovastatin in HER2-low and Ultralow Advanced or Metastatic Breast Cancer (MBC)
- ClinicalTrials.gov ID
- NCT07619365
- Acronym / sponsor ID
- 202606082
- Keywords
- Antibody drug conjugate, HER2 low, HER2 ultralow
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), The Foundation for Barnes-Jewish Hospital
- Study start
- 30 Nov 2026 (estimated)
- Primary completion
- 30 Nov 2030 (estimated)
- Study completion
- 30 Nov 2031 (estimated)
- First posted
- 2 Jun 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 purpose of this study is to evaluate the use of lovastatin, a cholesterol-depleting pro-drug that may lower CAV-1 levels, in order to increase HER2 expression on the cell surface of cancer cells and enhance the uptake and efficacy of trastuzumab deruxtecan (T-DXd) in HER2-low and ultralow breast tumors.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Safety Lead In: Trastuzumab Deruxtecan (T-DXd) + Lovastatin | Experimental | Drug: Trastuzumab deruxtecan, Drug: LovastatinT-DXd will be administered at a standard dose intravenously (IV) every 21 days and lovastatin will be administered orally at 20 mg with doses approximately 12 hours and 30 minutes before each cycle of T-DXd. Patients will be assessed for unacceptable toxicities during the first two treatment cycles. |
| Standard dose: Trastuzumab Deruxtecan (T-DXd) + Lovastatin | Experimental | Drug: Trastuzumab deruxtecan, Drug: LovastatinT-DXd will be administered at a standard dose intravenously (IV) every 21 days and lovastatin will be administered orally at 20 mg with doses approximately 12 hours and 30 minutes before each cycle of T-DXd. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Histologically or cytologically confirmed HER2 low (IHC 1+ or 2+ with negative in-situ hybridization) or ultralow (IHC 0 with incomplete/faint membrane staining in >0 but ≤10% of tumor cells) breast cancer based on the most recent biopsy. Patients may be advanced/unresectable or metastatic.
- Patients must have received no more than 1 prior line of chemotherapy (e.g. capecitabine). There is no limit on the prior number of endocrine-based therapies for patients with hormone-receptor positivity.
- Measurable disease per RECIST 1.1.
- At least 18 years of age.
- ECOG performance status ≤ 2
Key exclusion criteria (18 listed)
- Prior treatment with T-DXd or other topoisomerase I ADC including sacituzumab govitecan, datopotamab deruxtecan, or investigational ADCs with topoisomerase I payloads.
- Prior statin use within 7 days prior to C1D-1.
- Patients with unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to grade ≤1 or baseline. Participants with chronic grade 2 toxicities may be eligible per the discretion of the Investigator after consultation with the Study PI or designee (e.g., grade 2 chemotherapy-induced neuropathy).
- Prior or concurrent malignancy whose natural history has the potential to interfere with the safety or efficacy assessment of the investigational regimen. Patients with prior or concurrent malignancy that does NOT meet that definition are eligible for this trial
- Currently receiving any other investigational agents, or receipt of any investigational agents within 3 weeks or 5 half-lives, whichever is shorter, prior to C1D-1.
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 |
|---|---|---|
| Trastuzumab deruxtecanAlso: T-DXd, EnhertuStandard of care trastuzumab deruxtecan is administered at a starting dose of 5.4 mg/kg intravenously every 3 weeks according to package guidelines. The first infusion is administered over 90 minutes, and subsequent infusions may be administered over 30 minutes if prior infusions were well tolerated. | Drug | Safety Lead In: Trastuzumab Deruxtecan (T-DXd) + Lovastatin, Standard dose: Trastuzumab Deruxtecan (T-DXd) + Lovastatin |
| LovastatinAlso: Mevacor, Altoprev, AltocorLovastatin is provided in 10 mg and 20mg tablets for oral administration. It will be taken approximately 12 hours and 10 minutes before each T-DXd cycle. | Drug | Safety Lead In: Trastuzumab Deruxtecan (T-DXd) + Lovastatin, Standard dose: Trastuzumab Deruxtecan (T-DXd) + Lovastatin |
Primary outcome
Objective Response Rate (ORR)
Time frame: Start of treatment through end of treatment (estimated total time 12 months)
ORR is defined as the proportion of patients who achieve complete response (CR) or partial response (PR) according to RECIST v1.1. CR is defined as disappearance of all target lesions. Disappearance of all non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
4 secondary outcomes
Progression Free Survival (PFS)
Time frame: Start of treatment to date of progression, death, or date of last follow up whichever is earlier (total estimated time to be 24 months)
Overall Survival (OS)
Time frame: Start of treatment to date of progression, death, or date of last follow up (total estimated time to be 24 months)
Safety lead-in only: Rate of unacceptable toxicities
Time frame: Start of treatment to completion of Cycle 2 (each cycle is 3 weeks in length, estimated total time 6 weeks)
Number and type of adverse events (AEs)
Time frame: Start of treatment through 30 days post last dose of either study treatment, whichever is later (estimated total time 13 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 2 Nov 2026.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Andrew A Davis, MD principal investigator
Washington University School of Medicine
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 Trastuzumab deruxtecan and Lovastatin in people with Breast Cancer and Advanced Breast Cancer, run by Washington University School of Medicine at 1 site in United States.
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 16 inclusion and 18 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 2 Nov 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 United States. 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 Andrew A Davis, MD (314-362-5740, aadavis@wustl.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: Start of treatment through end of treatment (estimated total time 12 months)). 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 2 Nov 2026.