NCT03523572|CompletedPhase 1ResultsDMCFDA Drug

Trastuzumab Deruxtecan With Nivolumab in Advanced Breast and Urothelial Cancer

A Phase 1b, Multicenter, Two-Part, Open-Label Study of Trastuzumab Deruxtecan, an Anti-Human Epidermal Growth Factor Receptor-2 (HER2)-Antibody Drug Conjugate (ADC), in Combination With Nivolumab, an Anti-PD-1 Antibody, for Subjects With HER2-expressing Advanced Breast and Urothelial Cancer

Daiichi Sankyo ClinicalTrials.gov

Compare

2 other identifiers

DS8201-A-U1052018-000371-32

Study Type

interventional

Target

Locations

7 countries

Sites

Timeline

RegisteredMay 2018

StartedAug 2018

CompletionSep 2023

Brief Summary

This is a study of trastuzumab deruxtecan for the treatment of HER2-positive unresectable or metastatic breast cancer following two or more prior anti-HER2 based regimens. Participants will receive this study drug along with a cancer drug, an immune checkpoint inhibitor, anti-PD1, called nivolumab. The study will be done in two parts:

Part 1 is to identify the recommended dose to use for treatment.
Part 2 is to find out how well the combination works, and how safe and tolerable it is.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at P75+ for phase_1 breast-cancer

Timeline

Completed

Started Aug 2018

Typical duration for phase_1 breast-cancer

Geographic Reach

7 countries

29 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

5.1 years study duration

First Submitted

Initial submission to the registry

April 30, 2018

Completed

14 days until next milestone

First Posted

Study publicly available on registry

May 14, 2018

Completed

3 months until next milestone

Study Start

First participant enrolled

August 2, 2018

Completed

3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 22, 2021

Completed

2.1 years until next milestone

Study Completion

Last participant's last visit for all outcomes

September 12, 2023

Completed

1.4 years until next milestone

Results Posted

Study results publicly available

January 27, 2025

Completed

Last Updated

January 27, 2025

Status Verified

December 1, 2024

Enrollment Period

3 years

First QC Date

April 30, 2018

Results QC Date

August 10, 2022

Last Update Submit

December 11, 2024

Conditions

Breast Cancer Urothelial Carcinoma

Keywords

Human epidermal growth factor receptor-2HER2RefractoryMetastaticUrothelial cancerBreast Cancer

Outcome Measures

Primary Outcomes (2)

Number of Participants With Dose-Limiting Toxicities at 3.2 mg/kg and 5.4 mg/kg Dose Level in Participants With HER2-expressing Advanced Breast Cancer in Dose Escalation
A Dose-Limiting Toxicity (DLT) is defined as any Treatment Emergent Adverse Event not attributable to disease or disease-related processes that occurs during the DLT evaluation period (2 complete cycles during Part 1) and is Grade 3 or above according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Each cycle is 21 days. Low dose was set at 3.2 mg/kg and high dose was set at 5.4 mg/kg.
Cycles 1 and 2 (each cycle is 21 days)
Percentage of Participants With Objective Response Rate (ORR) Based on Independent Central Review in Participants With HER2-expressing Advanced Breast Cancer or Urothelial Cancer
The Objective Response Rate (ORR) was the defined as the percentage of participants who achieved a best overall response of confirmed Complete Response (CR) or Partial Response (PR), assessed by independent central review (ICR) committee based on RECIST version 1.1. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. Confirmed ORR based on ICR is reported. As prespecified in the protocol, participants enrolled in Part 1 were pooled according to their trastuzumab deruxtecan dose and HER2 expressing levels (HER2 positive or HER2 low) for efficacy analyses. Participants who were dosed at 5.4 mg/kg of trastuzumab deruxtecan and have HER2-positive expression Breast Cancer (IHC score 3+ or IHC score 2+/ISH+) in Part 1 were pooled with the same participants from Part 2 (in this case, participants enrolled in Cohort 1).
Every 6 weeks in the first year after Day 1 of Cycle 1 and thereafter every 12 weeks until disease progression or initiation of additional anticancer therapy and survival, up to 2 years 11.5 months (each cycle is 21 days)

Secondary Outcomes (7)

Duration of Response (DoR) in Participants With HER2-expressing Advanced Breast Cancer or Urothelial Cancer
Every 6 weeks in the first year after Day 1 of Cycle 1 and thereafter every 12 weeks until disease progression or initiation of additional anticancer therapy and survival, up to 5 years (each cycle is 21 days)
Percentage of Participants With Disease Control Rate (DCR) in Participants With HER2-expressing Advanced Breast Cancer or Urothelial Cancer
Every 6 weeks in the first year after Day 1 of Cycle 1 and thereafter every 12 weeks until disease progression or initiation of additional anticancer therapy and survival, up to 5 years (each cycle is 21 days)
Progression-Free Survival (PFS) in Participants With HER2-expressing Advanced Breast Cancer or Urothelial Cancer
Every 6 weeks in the first year after Day 1 of Cycle 1 and thereafter every 12 weeks until disease progression or initiation of additional anticancer therapy and survival, up to 5 years (each cycle is 21 days)
Time to Response (TTR) Based on Independent Central Review in Participants With HER2-expressing Advanced Breast Cancer or Urothelial Cancer
Every 6 weeks in the first year after Day 1 of Cycle 1 and thereafter every 12 weeks until disease progression or initiation of additional anticancer therapy and survival, up to 5 years (each cycle is 21 days)
Overall Survival (OS) in Participants With HER2-expressing Advanced Breast Cancer or Urothelial Cancer
Date of first dose of study drug to the date of death due to any cause, up to 5 years
+2 more secondary outcomes

Study Arms (6)

Dose Escalation (3.2 mg/kg)

EXPERIMENTAL

Participants with HER2-expressing breast cancer who received starting intravenous dose of trastuzumab deruxtecan at 3.2 mg/kg and a fixed intravenous dose of 360mg of nivolumab every 3 weeks (Q3W). Escalating/de-escalating doses of trastuzumab deruxtecan in combination with a flat dose of nivolumab was administered on Day 1 of each 21-day cycle. The DLT observation period will be the first 2 cycles.