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

Summary

Participation Requirements

Description

PRIMARY OBJECTIVE: I. To assess the effects of trastuzumab deruxtecan (DS-8201a) on Top1cc formation 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. ...

PRIMARY OBJECTIVE: I. To assess the effects of trastuzumab deruxtecan (DS-8201a) on Top1cc formation 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 Top1cc formation 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 (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. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 40 days.

Tracking Information