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

NCT ID: NCT06331169

Last Updated: 2024-08-30

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-07-31
• Study Completion Date: 2027-06-30

Brief Summary

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.

Conditions

Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Anlotinib dose escalation + trastuzumab deruxtecan

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

Group Type: EXPERIMENTAL

Anlotinib

Intervention Type: DRUG

Anlotinib is a new, orally administered tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptors (PDGFR), and c-kit.

Trastuzumab deruxtecan

Intervention Type: DRUG

Trastuzumab deruxtecan is an antibody-drug conjugate composed of an anti-HER2 (human epidermal growth factor receptor 2) antibody, a cleavable tetrapeptide-based linker, and a cytotoxic topoisomerase I inhibitor.

Interventions

Anlotinib

Anlotinib is a new, orally administered tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptors (PDGFR), and c-kit.

Intervention Type: DRUG

Trastuzumab deruxtecan

Trastuzumab deruxtecan is an antibody-drug conjugate composed of an anti-HER2 (human epidermal growth factor receptor 2) antibody, a cleavable tetrapeptide-based linker, and a cytotoxic topoisomerase I inhibitor.

Intervention Type: DRUG

Other Intervention Names

Anlotinib dihydrochloride; DS-8201

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Fudan University

OTHER

Sponsor Role: lead

Responsible Party

Jian Zhang,MD

Director of Phase I Clinical Trial Department; Professor, Chief physician of oncology department

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Jian Zhang

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Countries

China

Facility Contacts

Jian Zhang, MD,PhD

Role: primary

syner2000@163.com

+8664175590 ext. 85000

Other Identifiers

ALTER-BC-Ib-01

Identifier Type: -

Identifier Source: org_study_id