DS-8201a and Nivolumab in Advanced Breast and Urothelial Cancer
Research type
Research Study
Full title
A Phase 1b, Multicenter, Two-Part, Open-Label Study of DS-8201a, 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
IRAS ID
244726
Contact name
Alan Mart
Contact email
Sponsor organisation
Daiichi Sankyo, Inc.
Eudract number
2018-000371-32
Clinicaltrials.gov Identifier
127553, IND NUMBER
Duration of Study in the UK
1 years, 6 months, 14 days
Research summary
This study is being carried out to see if a potential new investigational drug called DS-8201a is effective and safe in treating breast or urothelial cancer when combined with an existing drug, nivolumab. Nivolumab is an approved drug for urothelial cancer but is not approved for the treatment of HER2-expressing breast cancer. In addition, the amount of nivolumab used in this study is not the approved dose.
This study will be conducted in two parts. Study drug, DS-8201a will be given in combination with nivolumab in Part 1 and Part 2 of the study. Participants with breast and urothelial cancer will be enrolled in Part 1 and Part 2 of the study. Participants in the UK will only take part in Part 2 of the study.
In Part 2, there are 4 treatment groups. Based on the cancer type, participants with breast cancer and urothelial cancer will be assigned to one of the four treatment groups. Each group will include either 15 or 30 participants.
The study involves a screening, treatment and follow up period.Participants will continue to receive treatment in this study until they experience toxicity (side effects that are severe), their disease worsens, they withdraw their consent from the study or it is decided by the study doctor or Sponsor to stop their participation. The length of their participation will vary based on their health and the study events, but on average will be approximately 9 months.
The following tests are involved: medical history, eye tests, blood and urine sampling, CT/MRI scans, ECHO/MUGA scans, Electocardiograch (ECG), vital signs, physical examination.Lay summary of study results
This is a Phase 1b, open-label, multicenter, study to evaluate the efficacy and safety of T-DXd (an anti-human epidermal growth factor receptor 2 [HER2] antibody drug conjugate) 5.4 mg/kg every 3 weeks in combination with 360 mg nivolumab, in participants with HER2-expressing advanced breast and urothelial cancer in participants enrolled in the US and Europe.
T-DXd 5.4 mg/kg in combination with 360 mg nivolumab every 3 weeks demonstrated a clinically meaningful objective response rate (ORR), and the responses were durable. The exploratory efficacy data suggest that combination of T-DXd with nivolumab has antitumor activity in HER2-positive and HER2-low Breast Cancer, as well as HER2 high-expressing urothelial cancer participants. The response rates observed in Breast Cancer participants, however, are similar to historical data observed with T-DXd as a single-agent in these patient populations.
The overall safety profile was generally consistent with previous studies for T-DXd monotherapy in participants with Breast Cancer, and the addition of nivolumab did not appear to cause any overall synergistic toxicity.
The overall safety profile in urothelial cancer participants was also consistent with the established safety profile of T-DXd in other indications, and with nivolumab monotherapy in participants with urothelial cancer. The addition of nivolumab also did not appear to cause any overall synergistic toxicity.
The most frequently reported treatment-emergent adverse events in both Breast Cancer and urothelial cancer participants were gastrointestinal events, and they were manageable with routine clinical practice.
Interstitial lung disease/pneumonitis is an important identified risk of T-DXd and generally managed using the established interstitial lung disease management guidelines for both Breast Cancer and urothelial cancer participants. Notably, no increased risk of interstitial lung disease was observed for the combination.
The benefit-risk profile of T-DXd in combination with nivolumab remains favourable in Breast Cancer and urothelial cancer participants and further investigation is required to assess the added value of this combination.REC name
London - Chelsea Research Ethics Committee
REC reference
18/LO/1817
Date of REC Opinion
15 Apr 2019
REC opinion
Further Information Favourable Opinion