Anlotinib With Trastuzumab Deruxtecan for Previously Treated HER2-Low Advanced 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)

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

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Anlotinib; Drug: Trastuzumab deruxtecan

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 Type: Interventional
• Enrollment (Estimated): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200433
      • Jian Zhang
      • Contact: Jian Zhang, MD,PhD; Phone Number: 85000 +8664175590; Email: syner2000@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	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.; Other Names: Anlotinib dihydrochloride; 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.; Other Names: DS-8201
Experimental: Anlotinib + trastuzumab deruxtecan combination therapy (dose expansion); Anlotinib at the RP2D + trastuzumab deruxtecan 5.4 mg/kg combination therapy .	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.; Other Names: Anlotinib dihydrochloride; 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.; Other Names: DS-8201

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: March 20, 2024
• First Submitted That Met QC Criteria: March 20, 2024
• First Posted (Actual): March 26, 2024

Study Record Updates

• Last Update Posted (Actual): March 26, 2024
• Last Update Submitted That Met QC Criteria: March 20, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Immunoconjugates; Trastuzumab; Trastuzumab deruxtecan
• Other Study ID Numbers: ALTER-BC-Ib-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No