Combining Anlotinib and Trastuzumab Deruxtecan for Advanced HER2-Low Breast Cancer

A Prospective Phase Ib Study of Anlotinib With Trastuzumab Deruxtecan for HER2-Low Unresectable and/or Metastatic Breast Cancer (ALTER-BC-Ib-01)

This study is testing if combining two drugs, anlotinib and trastuzumab deruxtecan, can help people with advanced HER2-low breast cancer who have already had one round of chemotherapy.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 42 (estimated)
• Ages: 18 Years to 75 Years
• Sex: Female
• Sponsor: Fudan University (Academic / other)
• Drugs / interventions: chemotherapy, trastuzumab, anlotinib
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT06331169 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety, tolerability, and efficacy of the combination of anlotinib and trastuzumab deruxtecan in patients with HER2-low unresectable or metastatic breast cancer who have previously received one line of chemotherapy. Participants will be monitored for their response to treatment and any adverse effects. The study aims to determine if this combination can provide a new treatment option for patients who have limited alternatives.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with unresectable or metastatic breast cancer that has low HER2 expression and has progressed after prior chemotherapy.

Not a fit: Patients with HER2-positive breast cancer or those who have not received prior chemotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a new therapeutic option for patients with advanced HER2-low breast cancer.

How similar studies have performed: While there is ongoing research in this area, the specific combination of anlotinib and trastuzumab deruxtecan for HER2-low breast cancer is relatively novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:

* 1\. Age 18 - 75 years; ECOG PS 0 or 1. 2. Pathologically documented breast cancer that:

  1. Is unresectable or metastatic.
  2. Has a history of low HER2 expression (IHC 1+\& IHC 2+/ISH- or 0\<IHC\<1+).
  3. Is HR-positive or HR-negative.
  4. Has progressed on, and would no longer benefit from, endocrine therapy.
  5. Has been treated with ≥1 prior lines of chemotherapy/adjuvant in the recurrent or metastatic setting.

     3\. At least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors version 1.1（Previously treated lesions with radiotherapy or focal therapy and no progression cannot be included as target lesion for assessment）.

     4\. Has protocol-defined adequate bone marrow, renal, hepatic and blood clotting functions.

     5\. Male and female subjects of reproductive/childbearing potential must agree to use a highly effective form of contraception or avoid intercourse during and upon completion of the study and after the last dose for at least 6 months.

     Exclusion Criteria:
     1. Has previously been treated with anti-angiogenic targeted small molecule therapy.
     2. Prior treatment with antibody drug conjugate with a topoisomerase I inhibitor exatecan derivative.
     3. Has a history of (noninfectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
     4. Has unresolved toxicities from previous anticancer therapy.
     5. Has uncontrolled or significant cardiovascular disease.
     6. Has any bleeding event, unhealed wounds, ulcerative or fractures.
     7. Has arterial or venous thromboembolic events occurred within 6 months.
     8. Has spinal cord compression or clinically active central nervous system metastases.
     9. Has any other condition that per protocol or in the opinion of the investigator is inappropriate for the study.

Where this trial is running

Shanghai, Shanghai Municipality

• Jian Zhang — Shanghai, Shanghai Municipality, China (Recruiting)

Conditions Breast Cancer