Efficacy and Safety of the Combination of Trastuzumab Plus TUCAtinib Plus viNorelbine in Patients With HER2-positive Non-resectable Locally Advanced or Metastatic Breast Cancer

Summary

Breast cancer (BC) is the most common neoplasm in the world. In Spain, one in 8 women is diagnosed with BC. The human epidermal growth factor receptor 2 (HER2)-positive BC subtype (that represents around 20% of all BC) was associated with poor prognosis however, new therapeutic advances have significantly increased the cure rate of patients in early stages.

In the metastatic setting, anti-HER2 targeted therapies have significantly improved overall survival (OS) with good quality of life, however there is still a substantial group of patients who die, and therefore additional drugs need to be investigated.

Trastuzumab, an anti HER2 antibody has demonstrated, in combination with chemotherapy, an improvement of OS in early and metastatic stages.

Tucatinib is an oral selective inhibitor of the HER2 receptor tyrosine kinase subunit. Its high affinity for this subunit causes fewer toxicities, such as rash and diarrhea, which are common with other anti-HER tyrosine kinase inhibitors (TKIs).

Vinorelbine has been evaluated previously in combination with trastuzumab showing interesting results.

This is a single country, multicenter, single arm phase II clinical trial with a safety run-in phase, to study the efficacy, safety and tolerability of the administration of tucatinib in combination with trastuzumab and vinorelbine in HER2-positive non-resectable locally advanced or metastatic breast cancer (MBC) with measurable disease.

Conditions

• HER2-positive Metastatic Breast Cancer
• Locally Advanced HER2 Positive Breast Carcinoma

Interventions

DRUG

Tucatinib

Run-in Phase: * Trastuzumab either IV or SC: 8 mg/kg IV loading dose (if necessary), followed by 6 mg/kg intravenous (IV) or 600 mg subcutaneous (SC) every 3 weeks. * Oral vinorelbine: 50 mg/m2 (in the first cycle) and 60 mg/m2 (in the following cycles if no dose limiting toxicity \[DLT\] is seen) on days 1 and 8, every 3 weeks. * Oral tucatinib 300 mg twice a day (BID) on a continuous dosing schedule. Following patients in the phase II: * Trastuzumab either IV or SC: 8 mg/kg IV loading dose (if necessary), followed by 6 mg/kg IV or 600 mg SC every 3 weeks. * Oral vinorelbine: 50 mg/m2 or 60 mg/m2 (based on the run-in phase results) on days 1 and 8, every 3 weeks. * Oral tucatinib 300 mg BID on a continuous dosing schedule.

DRUG

Trastuzumab

Run-in Phase: * Trastuzumab either IV or SC: 8 mg/kg IV loading dose (if necessary), followed by 6 mg/kg intravenous (IV) or 600 mg subcutaneous (SC) every 3 weeks. * Oral vinorelbine: 50 mg/m2 (in the first cycle) and 60 mg/m2 (in the following cycles if no dose limiting toxicity \[DLT\] is seen) on days 1 and 8, every 3 weeks. * Oral tucatinib 300 mg twice a day (BID) on a continuous dosing schedule. Following patients in the phase II: * Trastuzumab either IV or SC: 8 mg/kg IV loading dose (if necessary), followed by 6 mg/kg IV or 600 mg SC every 3 weeks. * Oral vinorelbine: 50 mg/m2 or 60 mg/m2 (based on the run-in phase results) on days 1 and 8, every 3 weeks. * Oral tucatinib 300 mg BID on a continuous dosing schedule.

DRUG

Vinorelbine

Run-in Phase: * Trastuzumab either IV or SC: 8 mg/kg IV loading dose (if necessary), followed by 6 mg/kg intravenous (IV) or 600 mg subcutaneous (SC) every 3 weeks. * Oral vinorelbine: 50 mg/m2 (in the first cycle) and 60 mg/m2 (in the following cycles if no dose limiting toxicity \[DLT\] is seen) on days 1 and 8, every 3 weeks. * Oral tucatinib 300 mg twice a day (BID) on a continuous dosing schedule. Following patients in the phase II: * Trastuzumab either IV or SC: 8 mg/kg IV loading dose (if necessary), followed by 6 mg/kg IV or 600 mg SC every 3 weeks. * Oral vinorelbine: 50 mg/m2 or 60 mg/m2 (based on the run-in phase results) on days 1 and 8, every 3 weeks. * Oral tucatinib 300 mg BID on a continuous dosing schedule.

Sponsors & Collaborators

• Seagen Inc.

  collaborator INDUSTRY

• Spanish Breast Cancer Research Group

  lead OTHER

Principal Investigators

• Study Director · Hospital General Universitario Gregorio Marañón, Madrid, Spain

• Study Director · Hospital Universitario Donostia, San Sebastián, Spain.

• Study Director · Hospital Universitario Reina Sofía, Córdoba, Spain

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-03-08

Primary Completion

2025-05-30

Completion

2025-05-30

Countries

• Spain

Study Locations