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

NCT06331169 | Recruiting Phase 1

• 1 other identifier: ALTER-BC-Ib-01
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (5)

• Duration of Response (DCR)

  Up to approximately 3 years

• Duration of Response (DOR)

  Up to approximately 3 years

• Progression-free Survival (PFS)

  Up to approximately 3 years

• Overall Survival (OS)

  Up to approximately 3 years

• Number of Participants With Adverse Events (AEs)

  Up to approximately 3 years

Study Arms (1)

Anlotinib dose escalation + trastuzumab deruxtecan

EXPERIMENTAL

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

Drug: Anlotinib; Drug: Trastuzumab deruxtecan

Interventions

Anlotinib 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.

Also known as: Anlotinib dihydrochloride

Anlotinib dose escalation + trastuzumab deruxtecan

Trastuzumab deruxtecan 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.

Also known as: DS-8201

Anlotinib dose escalation + trastuzumab deruxtecan

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Age 18 - 75 years; ECOG PS 0 or 1. 2. Pathologically documented breast cancer that:
• Is unresectable or metastatic.
• Has a history of low HER2 expression (IHC 1+\& IHC 2+/ISH- or 0\<IHC\<1+).
• Is HR-positive or HR-negative.
• Has progressed on, and would no longer benefit from, endocrine therapy.
• Has been treated with ≥1 prior lines of chemotherapy/adjuvant in the recurrent or metastatic setting.
• \. 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）.
• \. Has protocol-defined adequate bone marrow, renal, hepatic and blood clotting functions.
• \. 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.

You may not qualify if:

• Has previously been treated with anti-angiogenic targeted small molecule therapy.
• Prior treatment with antibody drug conjugate with a topoisomerase I inhibitor exatecan derivative.
• 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.
• Has unresolved toxicities from previous anticancer therapy.
• Has uncontrolled or significant cardiovascular disease.
• Has any bleeding event, unhealed wounds, ulcerative or fractures.
• Has arterial or venous thromboembolic events occurred within 6 months.
• Has spinal cord compression or clinically active central nervous system metastases.
• Has any other condition that per protocol or in the opinion of the investigator is inappropriate for the study.

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Jian Zhang

Shanghai, Shanghai Municipality, 200433, China

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

anlotinib; trastuzumab deruxtecan

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Phase I Clinical Trial Department; Professor, Chief physician of oncology department

Study Record Dates

• First Submitted: March 20, 2024
• First Posted: March 26, 2024
• Study Start: July 31, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): June 30, 2027
• Last Updated: August 30, 2024

Record last verified: 2024-03

Locations

CN (1)