NCT04042701

DS8201a and Pembrolizumab in Participants With Locally Advanced/Metastatic Breast or Non-Small Cell Lung Cancer

A Phase 1b, Multicenter, Two-Part, Open-Label Study of Trastuzumab Deruxtecan (DS-8201a), An Anti-Human Epidermal Growth Factor Receptor-2 (HER2)-Antibody Drug Conjugate (ADC), In Combination With Pembrolizumab, An Anti-PD-1 Antibody, For Subjects With Locally Advanced/Metastatic Breast Or Non-Small Cell Lung Cancer (NSCLC)

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 115 (estimated)
• Sponsor: Daiichi Sankyo · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This two-part study will include a dose escalation part to determine the recommended dose for expansion of DS8201a and pembrolizumab and a dose expansion part to evaluate efficacy, safety, and tolerability of the combination.

Detailed description

This phase 1b, open-label, 2-part, multicenter, non-randomized, multiple-dose study will evaluate DS-8201a in combination with pembrolizumab in participants with advanced/metastatic breast cancer or non-small cell lung cancer (NSCLC). In the dose escalation part of the study, escalating doses of DS-8201a in combination with pembrolizumab will be assessed. DS-8201a and pembrolizumab 200 mg will be administered on Day 1 of every 21-day cycle. The initial dose administered for DS8201a will be 3.2 mg/kg Q3W. Escalation to the next dose (5.4 mg/kg Q3W) will be based on acceptable safety signals based on the earlier dose cohort. Upon completion of dose escalation with the recommended dose of escalation (RDE) established, the dose expansion part of the study will begin. The dose expansion part will include 4 cohorts: Human epidermal growth factor receptor 2 (HER2+) breast cancer participants with prior ado-trastuzumab emtansine (T-DM1), HER2 low breast cancer participants with prior failed standard treatments, HER2-expressing NSCLC participants who have not received any prior treatment with anti-PD-1, anti-PD-L1, or HER2 agents, and HER2-mutant NSCLC participants who have not received any prior treatment with anti-PD-1, anti-PD-L1, or HER2 agents.

Conditions

• Breast Cancer
• Non-small Cell Lung Carcinoma

Interventions

Type	Name	Description
DRUG	Trastuzumab deruxtecan (DS-8201a)	Part 1: Two dose levels of DS-8201a (3.2 mg/kg Q3W and 5.4 mg/kg Q3W via intravenous (IV) infusion will be administered for the dose escalation part of the study in combination with pembrolizumab. Part 2: Once Part 1 of the study is complete and a RDE for DS-8201a has been established, Part 2 will begin. All participants will receive DS-8201a at the RDE in combination with pembrolizumab.
DRUG	Trastuzumab deruxtecan (DS-8201a)	Part 1: Two dose levels of DS-8201a (3.2 mg/kg Q3W and 5.4 mg/kg Q3W via intravenous (IV) infusion will be administered for the dose escalation part of the study in combination with pembrolizumab. Part 2: Once Part 1 of the study is complete and a RDE for DS-8201a has been established, Part 2 will begin.
DRUG	Pembrolizumab	All participants will receive pembrolizumab (200 mg Q3W) via intravenous (IV) infusion prior to DS-8201a in Parts 1 and 2 of the study.

Timeline

• Start date: 2020-02-10
• Primary completion: 2025-07-21
• Completion: 2027-03-31
• First posted: 2019-08-02
• Last updated: 2025-11-18

Locations

30 sites across 4 countries: United States, France, Spain, United Kingdom

Regulatory

• FDA-regulated drug study