Title
A Phase 1b/2 Open-Label Study of Disitamab Vedotin Monotherapy or in Combination with Other Anticancer Therapies in Solid Tumors

Description
This clinical trial is studying solid tumor cancers. A solid tumor is one that starts in part of your body like your lungs or liver instead of your blood. Once they've grown bigger in one spot or spread to other parts of the body, they're harder to treat. This is called advanced or metastatic cancer.

Participants in this study must have breast cancer or gastric cancer. Participants must have tumors that have HER2 on them. This allows the cancer to grow more quickly or spread faster. There are few treatment options for patients with advanced or metastatic solid tumors that express HER2.

This clinical trial uses an experimental drug called disitamab vedotin (DV). Disitamab vedotin is a type of antibody drug conjugate or ADC. ADCs are designed to stick to cancer cells and kill them.

This clinical trial uses a drug called tucatinib, which has been approved to treat cancer in the United States and some other countries. This drug is sold under the brand name TUKYSA®.

This study will test how safe and how well DV, with or without tucatinib, is for participants with solid tumors. This study will also test what side effects happen when participants take these drugs. A side effect is anything a drug does to the body besides treating the disease.

Objective
Primary:
-To identify the maximum tolerated dose (MTD) and/or optimal dose of disitamab vedotin when administered in combination with tucatinib.

-To characterize the safety and tolerability of disitamab vedotin monotherapy regimens in:
-HER2-low 2L or 3L advanced BC
-HER2+ 3L+ advanced BC
-HER2-low 2L advanced GC/GEJC

-To characterize the safety and tolerability of disitamab vedotin plus tucatinib in:
-HER2-low 2L or 3L advanced BC
-HER2+ 3L+ advanced BC
-HER2-low 2L advanced GC/GEJC

-To assess the antitumor activity of disitamab vedotin monotherapy in:
-HER2-low 2L or 3L advanced BC
-HER2+ 3L+ advanced BC
-HER2-low 2L advanced GC/GEJC

-To assess the antitumor activity of disitamab vedotin plus tucatinib in:
-HER2-low 2L or 3L advanced BC
-HER2+ 3L+ advanced BC
-HER2-low 2L advanced GC/GEJC

Treatment This clinical trial is to evaluate disitamab vedotin alone and in combination with tucatinib in subjects with LA/metastatic breast cancer or gastric cancer/GEJC that express HER2. The study has a dose escalation phase evaluating disitamab vedotin plus tucatinib followed by a dose optimization phase. The 2 dose levels identified in the dose escalation phase will be assessed in the optimization phase for both safety and efficacy in HER2-low LA/mBC subjects. Once the safety and efficacy profile of disitamab vedotin plus tucatinib has been established and a disitamab vedotin dose with the optimum benefit/risk ratio has been determined the disitamab vedotin plus tucatinib combination therapy will be evaluated in an expansion phase with 2 expansion cohorts in subjects with HER2 low mGC/GEJC and HER2 + LA/mBC.

Key Eligibility For full study eligibility, see this study's ClinicalTrials.gov record.

Applicable Disease Sites
Breast; Esophagus; Stomach

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital