Trastuzumab Deruxtecan and Lovastatin in HER2-low and Ultralow Advanced or Metastatic Breast Cancer

NCT07619365 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 26-x146
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate use of lovastatin, a drug that may lower CAV-1 levels, in order to increase HER2 expression on cells and enhance the uptake and efficacy of trastuzumab deruxtecan (T-DXd) in HER2-low and ultralow advanced metastatic breast cancer. Trastuzumab deruxtecan (T-DXd) is an FDA approved antibody drug conjugate for HER2-low and ultralow breast cancer and lovastatin is a cholesterol lowering agent.

Conditions

Breast Cancer; Advanced Breast Cancer; Metastatic Breast Cancer

Keywords

Antibody drug conjugate; HER2 low; HER2 ultralow

Outcome Measures

Primary Outcomes (1)

• 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.

  Start of treatment through end of treatment (estimated total time 12 months)

Secondary Outcomes (4)

• Progression Free Survival (PFS)

  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)

  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

  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)

  Start of treatment through 30 days post last dose of either study treatment, whichever is later (estimated total time 13 months)

Study Arms (2)

Safety Lead In: Trastuzumab Deruxtecan (T-DXd) + Lovastatin

EXPERIMENTAL

T-DXd will be administered at a standard dose intravenously (IV) every 3 weeks 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.10 patients enrolled in either the safety lead-in or enrolled after the safety lead-in is completed will undergo a pre- and on-treatment biopsy for pharmacodynamic assessment.

Drug: Trastuzumab deruxtecan; Drug: Lovastatin

Standard dose: T-DXd + Lovastatin

EXPERIMENTAL

T-DXd will be administered at a standard dose intravenously (IV) every 3 weeks and lovastatin will be administered orally at 20 mg with doses approximately 12 hours and 30 minutes before each cycle of T-DXd. 10 patients enrolled in either the safety lead-in or enrolled after the safety lead-in is completed will undergo a pre- and on-treatment biopsy for pharmacodynamic assessment.

Drug: Trastuzumab deruxtecan; Drug: Lovastatin

Interventions

Trastuzumab deruxtecan DRUG

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.

Also known as: T-DXd, Enhertu

Safety Lead In: Trastuzumab Deruxtecan (T-DXd) + Lovastatin; Standard dose: T-DXd + Lovastatin

Lovastatin DRUG

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.

Also known as: Mevacor, Altoprev, Altocor

Safety Lead In: Trastuzumab Deruxtecan (T-DXd) + Lovastatin; Standard dose: T-DXd + Lovastatin

Eligibility Criteria

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

You may qualify if:

• 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. 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:
• 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 \> 30 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Breast Neoplasms

Interventions

trastuzumab deruxtecan; Lovastatin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Andrew A Davis, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrew A Davis, MD

CONTACT

314-362-5740; aadavis@wustl.edu

Study Design

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

Study Record Dates

• First Submitted: May 21, 2026
• First Posted: June 2, 2026
• Study Start (Estimated): August 31, 2026
• Primary Completion (Estimated): August 31, 2030
• Study Completion (Estimated): August 31, 2031
• Last Updated: June 2, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)