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Breast Diseases

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Trastuzumab

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Tucatinib

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Tucatinib (ONT-380)

T-DM1

JoAl Mayor, PharmD, BCOP

Corinna Palanca-Wessels, MD, PhD

The purpose of this study is to determine the maximal tolerated dose (MTD) or recommended dose (RD) and to assess the safety and tolerability of tucatinib (ONT-380) combined with ado-trastuzumab emtansine (T-DM1) in patients with HER2+ breast cancer.

This is a Phase 1b, open-label study of tucatinib (ONT-380) given in combination with ado-trastuzumab emtansine (T-DM1) to patients with HER2+ breast cancer.

This study will use a 3+3 dose escalation design to evaluate up to four dose levels of tucatinib ONT-380 in order to identify the maximal tolerated dose/recommended dose (MTD/RD) of tucatinib (ONT-380) in combination with T-DM1. T-DM1 will be administered intravenously on day 1 of each cycle (except cycle 1, when it will be administered on day 2 to allow for PK assessments of tucatinib (ONT-380) alone).Tucatinib (ONT-380) will be administered orally, twice per day on days 1-21 of each cycle.

There will be 3-6 evaluable patients enrolled in each cohort in the dose escalation phase, unless that dose is found to be intolerable prior to completion of enrollment. At least 6 evaluable patients are to be treated at a dose level in order for an MTD/RD to be declared. Once an MTD/RD is declared, an additional 24 evaluable patients will be in enrolled in a MTD/RD expansion cohort for a total of 30 evaluable patients to be treated at the MTD/RD.

In addition to the MTD/RD expansion cohort, an optional additional cohort of up to 15 evaluable patients with either untreated, asymptomatic CNS metastases not needing immediate local therapy or progressive CNS metastasis following local therapy may also be enrolled and treated at the MTD/RD. Up to 63 evaluable patients may be treated in this study.

A Study of Tucatinib (ONT-380) Combined With Ado-trastuzumab Emtansine (T-DM1) in Patients With HER2+ Breast Cancer

A Phase 1b, Open-label Study to Assess the Safety and Tolerability of Tucatinib (ONT-380) Combined With Ado-trastuzumab Emtansine (Trastuzumab Emtansine; T-DM1)

Defined as best response of complete response (CR), partial response (PR), or stable disease (SD)

Seagen Inc.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Tucatinib (ONT-380) Combined With Ado-trastuzumab Emtansine (T-DM1) in Patients With HER2+ Breast Cancer	NCT01983501	HER2 Positive B...	Tucatinib (ONT-... T-DM1	18 Years -	Seagen Inc.
A Study of Tucatinib (ONT-380) Combined With Ado-trastuzumab Emtansine (T-DM1) in Patients With HER2+ Breast Cancer	NCT01983501	HER2 Positive B...	Tucatinib (ONT-... T-DM1	18 Years -	Seagen Inc.
A Study of Tucatinib (ONT-380) Combined With Ado-trastuzumab Emtansine (T-DM1) in Patients With HER2+ Breast Cancer	NCT01983501	HER2 Positive B...	Tucatinib (ONT-... T-DM1	18 Years -	Seagen Inc.

Spots Global Cancer Trial Database for her2 positive breast cancers