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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06331169
• Other study ID #: ALTER-BC-Ib-01
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: April 1, 2024
• Est. completion date: June 30, 2027

Study information

• Verified date: March 2024
• Source: Fudan University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A Prospective Phase Ib Study of Anlotinib with Trastuzumab Deruxtecan for HER2-Low Unresectable and/or Metastatic Breast Cancer

Description:

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 42
• Est. completion date: June 30, 2027
• Est. primary completion date: December 31, 2026
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Age 18 - 75 years;

2. ECOG PS 0 or 1.

3. . 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 = 2 prior lines of chemotherapy/adjuvant in the recurrent or metastatic setting.

4. At least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors version 1.1.

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

6. 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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• 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.
• 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.

Locations

Country	Name	City	State
China	Jian Zhang	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Fudan University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determination of the RP2D of anlotinib in combination with trastuzumab deruxtecan	The RP2D is defined as the dose level for the dose expansion phase, based on safety, tolerability, efficacy collected during the dose escalation portion of the study.	up to 1 year
Primary	Objective Response Rate (ORR)	ORR defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.	Up to approximately 3 years
Secondary	Duration of Response (DCR)	DCR is defined as the percentage of cases with remission (PR+CR) and stable disease (SD) after treatment in the evaluable cases.	Up to approximately 3 years
Secondary	Duration of Response (DOR)	DOR is defined as the time from the participant's initial objective response to the first date of either disease progression or death, whichever occurs first.	Up to approximately 3 years
Secondary	Progression-free Survival (PFS)	PFS is defined as the time from the participant's first dose of study treatment to the first date of either disease progression or death, whichever occurs first.	Up to approximately 3 years
Secondary	Overall Survival (OS)	OS is defined as the time from the participant's first dose of study treatment to the date of death.	Up to approximately 3 years
Secondary	Number of Participants With Adverse Events (AEs)	Assessment of the toxicity profile of regimen according to the National Cancer Institute Common Toxicity Criteria version 5.0 (NCI CTCAE v 5.0).	Up to approximately 3 years