Anlotinib With Trastuzumab Deruxtecan for Previously Treated HER2-Low Advanced Breast Cancer

Fudan University

Status and phase: Enrolling; Phase 1

Conditions: Breast Cancer

Treatments: Drug: Trastuzumab deruxtecan; Drug: Anlotinib

Study type: Interventional

Funder types: Other

Identifiers

NCT06331169

ALTER-BC-Ib-01

Details and patient eligibility

About

This study will evaluate the safety, tolerability and efficacy of anlotinib and trastuzumab deruxtecan in human epidermal growth factor receptor 2 (HER2)-low unresectable and/or metastatic breast cancer who had received ≤1 line of prior chemotherapy.

Enrollment: 42 estimated patients

Sex: Female

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

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

  2. Is unresectable or metastatic.

  3. Has a history of low HER2 expression (IHC 1+& IHC 2+/ISH- or 0<IHC<1+).

  4. Is HR-positive or HR-negative.

  5. Has progressed on, and would no longer benefit from, endocrine therapy.

  6. 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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Sequential Assignment

Masking: None (Open label)

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42 participants in 1 patient group

Anlotinib dose escalation + trastuzumab deruxtecan

Experimental group

Description:

Various doses of anlotinib (8 mg QD, 10 mg QD, and 12 mg QD) administered during dose escalation to determine the recommended phase 2 Dose (RP2D) + trastuzumab deruxtecan 5.4 mg/kg. Anlotinib at the RP2D + trastuzumab deruxtecan 5.4 mg/kg combination therapy

Treatment:

Drug: Trastuzumab deruxtecan

Drug: Anlotinib