Testing the Biological Effects of DS-8201a on Patients With Advanced Cancer

Advanced Malignant Solid Neoplasm Clinical Trial

Official title: Pilot Study of DS-8201a Pharmacodynamics in Patients With HER2-Expressing Advanced Solid Tumors

Status Active, not recruiting

Clinical Trial Summary

This phase I trial studies the biological effects of DS-8201a on patients with HER2 positive cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). DS-8201a works by binding to a protein called HER2 that is present on the surface of tumor cells. This allows DS-8201a to kill the tumor cells by damaging their deoxyribonucleic acid (DNA), resulting in tumor cell death. This study looks at how DS-8201a may affect the levels of certain proteins and immune cells in tumors and how well the drug works against tumor cells by examining cells from a small piece tumor taken before and after DS-8201a is given.

Clinical Trial Description

PRIMARY OBJECTIVE:

I. To assess the effects of trastuzumab deruxtecan (DS-8201a) on total Top1 levels in biopsy specimens from patients with HER2-expressing advanced solid tumors, at early and late post-treatment time points, thereby establishing the degree and duration of DS-8201 target engagement.

SECONDARY OBJECTIVES:

I. To assess any associations between serum concentrations of DS-8201a and the effects of DS-8201a on total Top1 levels in tumor biopsy specimens.

II. To determine the safety and tolerability of DS-8201a administered intravenously every 3 weeks, in 21-day cycles, at a dose of 5.4 mg/kg.

III. To determine the overall response rate (complete response [CR] + partial response [PR]) for patients administered intravenously with DS-8201a every 3 weeks, in 21-day cycles, at a dose of 5.4 mg/kg.

EXPLORATORY OBJECTIVES:

I. To evaluate the effects of DS-8201a on CD8+ T cell infiltration and activation in tumor, tumor PD-L1 and HER2 expression, and DDR signaling (for example: gamma H2AX, RAD51, and phosphorylated [p]NBS1) in biopsy specimens.

II. To examine genomic alterations in circulating tumor DNA (ctDNA) that may be associated with DS-8201a response or resistance.

III. To examine any associations between baseline tumor HER2 amplification or HER2 expression level and response to DS-8201a.

IV. To evaluate the effects of DS-8201a on tumor levels of HER2 and DDR-associated proteins.

V. To examine any tumor genomic alterations that may be associated with resistance to DS-8201a.

VI. To evaluate anti-drug antibodies following administration of DS-8201a.

OUTLINE:

Patients receive trastuzumab deruxtecan intravenously (IV) over 30-90 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo echocardiography (ECHO) or multigated acquisition scan (MUGA), computed tomography (CT) or magnetic resonance imaging (MRI), biopsies, and collection of blood samples throughout the study.

After completion of study treatment, patients are followed up for 40 days. ;

Related Conditions & MeSH terms

• Advanced Malignant Solid Neoplasm
• Breast Neoplasms
• Metastatic Malignant Solid Neoplasm
• Neoplasms
• Refractory Malignant Solid Neoplasm
• Unresectable Malignant Solid Neoplasm

• NCT number: NCT04294628
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: September 1, 2020
• Completion date: December 31, 2025