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

Phase 1

Not yet recruiting

• Conditions: Breast Cancer
• Interventions: Drug: Anlotinib; Drug: Trastuzumab deruxtecan

• Registration Number: NCT06331169
• Lead Sponsor: Fudan University

Brief Summary

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

Detailed 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.

Study Timeline

• Status Verified: 2024-03
• Study First Submitted: 2024-03-20
• Study First Submitted QC: 2024-03-20
• Last Update Submitted: 2024-03-20
• Study First Posted: 2024-03-26
• Last Update Posted: 2024-03-26
• Study Start: 2024-04-01
• Primary Completion: 2026-12-31
• Study Completion: 2027-06-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 42

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Anlotinib dose escalation + trastuzumab deruxtecan	Anlotinib	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
Anlotinib dose escalation + trastuzumab deruxtecan	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

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	Up to approximately 3 years	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.
Determination of the RP2D of anlotinib in combination with trastuzumab deruxtecan	up to 1 year	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.

Secondary Outcome Measures

Name	Time	Method
Duration of Response (DCR)	Up to approximately 3 years	DCR is defined as the percentage of cases with remission (PR+CR) and stable disease (SD) after treatment in the evaluable cases.
Duration of Response (DOR)	Up to approximately 3 years	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.
Progression-free Survival (PFS)	Up to approximately 3 years	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.
Overall Survival (OS)	Up to approximately 3 years	OS is defined as the time from the participant's first dose of study treatment to the date of death.
Number of Participants With Adverse Events (AEs)	Up to approximately 3 years	Assessment of the toxicity profile of regimen according to the National Cancer Institute Common Toxicity Criteria version 5.0 (NCI CTCAE v 5.0).

Trial Locations

Locations (1)

Jian Zhang; 🇨🇳 Shanghai, Shanghai, China