A Study of T-DXd in Participants With or Without Brain Metastasis Who Have Previously Treated Advanced or Metastatic HER2 Positive Breast Cancer (DESTINY-Breast 12)

JRCT ID: jRCT2031210182

Registered date:02/07/2021

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Breast Cancer
• Date of first enrollment: 19/08/2021
• Target sample size: 500
• Countries of recruitment: Belgium,Japan,Denmark,Japan,Finland,Japan,Germany,Japan,Ireland,Japan,Italy,Japan,Netherlands,Japan,Norway,Japan,Poland,Japan,Portugal,Japan,Russia,Japan,Spain,Japan,Sweden,Japan,Switzerland,Japan,United Kingdom,Japan,Canada,Japan,United States,Japan,Australia,Japan
• Study type: Interventional

Intervention(s)

Drug: Trastuzumab Deruxtecan
Participants will receive T-DXd administered using an IV bag containing 5% (w/v) dextrose injection infusion solution.

Outcome(s)

Primary Outcome

-Objective Response Rate (ORR) in Participants without BM at Baseline (Cohort 1)
-Progression-free Survival in Participants with BM at Baseline (Cohort 2)

Secondary Outcome

Participants in both cohorts:
-OS
-DoR by RECIST per ICR
-Time to progression by RECIST per ICR
-DoT on subsequent lines of therapy
-PFS2
Participants without BM at baseline (Cohort 1):
-Incidence of new symptomatic CNS metastasis during treatment
In patients who develop isolated CNS progression, receive local therapy, and continue on protocol therapy:
-Time to next progression (CNS or extracranial) or death
-Site (CNS vs extracranial vs both) of next progression

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

-Participant must be >= 18 years at the time of screening.
Pathologically documented breast cancer that
-Is unresectable/advanced or metastatic, and
-Has confirmed HER2-positive status as determined according to ASCO/CAP guidelines
Participant must have untreated BM on screening contrast brain MRI/CT scan
(i)not needing immediate local therapy, or
(ii)For participants with untreated CNS lesions > 2.0 cm, discussion with and approval from the study physician is required prior to enrollment
Previously-treated stable or progressing BM
(i) Previously-treated BM with local therapy may either be radiographically stable for >= 4 weeks since treatment or may have progressed since prior local CNS therapy, provided that there is no clinical indication for immediate re-treatment with local therapy
(ii) Patients treated with CNS local therapy for newly identified lesions found on contrast brain MRI/CT scan performed during screening
-ECOG performance status 0-1
-Previous breast cancer treatment
(i)Radiologic or objective evidence of disease progression on trastuzumab, pertuzumab, or T-DM1.
(ii)No more than 2 lines/regimens of therapy in the metastatic setting.
-Adequate organ and bone marrow function

Exclude criteria

-Known or suspected LMD.
-Participants with a medical history of myocardial infarction within 6 months before screening, symptomatic CHF (NYHA Class II to IV), unstable angina pectoris, or a recent (< 6 months) cardiovascular event including stroke.
-History of (non-infectious) ILD/pneumonitis that required steroids, has current
-ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
Lung criteria:
(i) Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (eg, pulmonary emboli within 3 months of study
enrollment, severe asthma, severe COPD, restrictive lung disease, pleural effusion, etc)
(ii) Any autoimmune, connective tissue or inflammatory disorders (ie, rheumatoid arthritis, Sjogren's, sarcoidosis, etc.) where there is documented, or a suspicion of pulmonary involvement at the time of screening. Full details of the disorder should be recorded in the eCRF for participants who are included in the study.
(iii) Prior pneumonectomy
-Participation in another clinical study with a study intervention or investigational medicinal device administered in the last 30 days or 5 half-lives, whichever is longer, prior to first dose of study intervention, randomization into a prior T-DXd study regardless of treatment assignment, or concurrent enrollment in another clinical study,
unless it is an observational (noninterventional) clinical study or during the follow-up period of an interventional study.

Related Information

• Primary Sponsor: Hanai Masaharu
• Secondary Sponsor: AstraZeneca
• Secondary ID(s): NCT04739761