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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06018337




Registration number
NCT06018337
Ethics application status
Date submitted
25/08/2023
Date registered
30/08/2023

Titles & IDs
Public title
A Study of DB-1303/BNT323 vs Investigator's Choice Chemotherapy in HER2-Low, Hormone Receptor Positive Metastatic Breast Cancer (DYNASTY-Breast02)
Scientific title
A Phase 3, Randomized, Multi-center, Open-Label Study of DB-1303 Versus Investigator's Choice Chemotherapy in Human Epidermal Growth Factor Receptor 2 (HER2)-Low, Hormone Receptor Positive (HR+) Metastatic Breast Cancer Patients Whose Disease Has Progressed on Endocrine Therapy (ET) (DYNASTY-Breast02)
Secondary ID [1] 0 0
CTR20233708
Secondary ID [2] 0 0
DB-1303-O-3002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - DB-1303/BNT323
Treatment: Drugs - Capecitabine
Treatment: Drugs - Paclitaxel
Treatment: Drugs - Nab-paclitaxel

Experimental: DB-1303/BNT323 - Enrolled Subjects will be randomized to receive a 8 mg/kg IV dose of DB-1303/BNT323 on Day 1 of each cycle Q3W

Active comparator: investigator's choice single agent chemotherapy - Enrolled Subjects will be randomized to receive investigator's choice single agent chemotherapy (capecitabine:1000 or 1250 mg/m2, Oral, Twice daily orally for 2 weeks followed by a 1-week rest period in 3-week cycles; paclitaxel:80 mg/m2, IV, Every week (QW) in 3-week cycles; or nab-paclitaxel: 100 mg/m2, IV, Every week (QW) for 3 weeks followed by a one-week rest period in 4-week cycles) until RECIST 1.1 defined disease progression (PD), unless there is unacceptable toxicity, withdrawal of consent, or another criterion for discontinuation is met.


Treatment: Drugs: DB-1303/BNT323
IV

Treatment: Drugs: Capecitabine
Oral

Treatment: Drugs: Paclitaxel
IV

Treatment: Drugs: Nab-paclitaxel
IV
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free survival (PFS) in the HR+, HER2-low population
Timepoint [1] 0 0
Up to approximately 51 months
Secondary outcome [1] 0 0
Overall survival (OS) in the HR+, HER2-low population
Timepoint [1] 0 0
Up to approximately 51 months
Secondary outcome [2] 0 0
Objective response rate (ORR) in the HR+, HER2-low population
Timepoint [2] 0 0
Up to approximately 51 months
Secondary outcome [3] 0 0
PFS by Investigator assessment
Timepoint [3] 0 0
Up to approximately 51 months
Secondary outcome [4] 0 0
Duration of response (DoR) in the HR+, HER2-low population
Timepoint [4] 0 0
Up to approximately 51 months
Secondary outcome [5] 0 0
Treatment-emergent adverse events (TEAEs)
Timepoint [5] 0 0
from the time of the subject signing the informed consent form (ICF) until the follow-up period is completed (35 days after the last dose of study treatment
Secondary outcome [6] 0 0
Serious adverse events (SAEs)
Timepoint [6] 0 0
from the time of the subject signing the ICF until the follow-up period is completed (35 days after the last dose of study treatment
Secondary outcome [7] 0 0
Patient reported outcomes (PROs): European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) - C30
Timepoint [7] 0 0
Up to approximately 51 months
Secondary outcome [8] 0 0
Patient reported outcomes (PROs): EORTC QLQ-BR45
Timepoint [8] 0 0
Up to approximately 51 months
Secondary outcome [9] 0 0
Patient reported outcomes (PROs): European Quality of Life Five Dimension Five Level Scale (EQ-5D-5L)
Timepoint [9] 0 0
Up to approximately 51 months
Secondary outcome [10] 0 0
European Quality of Life Five Dimension Five Level Scale (EQ-5D-5L)
Timepoint [10] 0 0
Up to approximately 51 months

Eligibility
Key inclusion criteria
1. Male or female adults (defined as = 18 years of age or acceptable age according to local regulations at the time of voluntarily signing of informed consent).

2. Pathologically documented breast cancer that:

1. Is advanced or metastatic
2. Has HER2-low expression (IHC 1+ or IHC 2+/ISH-) as determined by the central laboratory result.
3. Was never previously reported as HER2-positive (IHC 3+ or ISH+) as per American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines.
4. Is documented as HR+ (either estrogen receptor [ER] and/or progesterone receptor [PgR] positive [ER or PgR =1%]) per ASCO/CAP guidelines (Allison et al 2020).

3. Must have an adequate tumor tissue sample available for assessment of HER2 by central laboratory, in formalin fixation and paraffin embedding (FFPE) blocks based on a mandatory FFPE tumor sample preferably obtained at the time of metastatic disease or later;

4. Eastern Cooperative Oncology Group performance status of 0 or 1.

5. Must have had either:

1. Disease progression on endocrine therapy + CDK4/6 inhibitor within 6 months of starting first line treatment for metastatic disease and considered appropriate for chemotherapy as the next treatment by the investigator, OR
2. Disease progression on at least 2 previous lines of ET with or without a targeted therapy (such as CDK4/6, mammalian target of rapamycin [mTOR] or phosphoinositide 3-kinase [PI3-K] inhibitors) administered for the treatment of metastatic disease.

6. No prior chemotherapy for advanced or metastatic breast cancer. Subjects who have received chemotherapy in the neo-adjuvant or adjuvant setting are eligible, as long as they have had a disease-free interval (defined as completion of systemic chemotherapy to diagnosis of advanced or metastatic disease) of >12 months.

7. Life expectancy =12 weeks at screening.

8. Subjects must have at least one measurable lesion as defined per RECIST v1.1 (For bone only disease, subjects with lytic or mixed lytic bone lesions that can be measured by CT or MRI are eligible; subjects with sclerotic/osteoblastic bone lesions are not eligible).

9. Has LVEF = 50% by either echocardiography (ECHO) or multiple-gated acquisition (MUGA) within 28 days before randomization.

10. Adequate organ and bone marrow function within 14 days before randomization.

11. Has adequate treatment washout period before randomization.

12. Evidence of post-menopausal status or negative serum pregnancy test for females of childbearing potential who are sexually active with a non-sterilized male partner. For women of childbearing potential, a negative result for serum pregnancy test (test must have a sensitivity of at least 25 mIU/mL) must be available at the screening visit and urine beta-human chorionic gonadotropin (ß-HCG) pregnancy test prior to each administration of study treatment.

Women of childbearing potential are defined as those who are not surgically sterile (i.e., underwent bilateral salpingectomy, bilateral oophorectomy, or complete hysterectomy) or post-menopausal.

13. Female subjects of childbearing potential who are sexually active with a non-sterilized male partner must use at least one highly effective method of contraception from the time of screening and must agree to continue using such precautions for 7 months after the last dose of study treatment. Not all methods of contraception are highly effective. Abstinence is acceptable only as true abstinence when this is in line with the preferred and usual lifestyle of the subject for the duration of the study treatment and the drug washout period (7 months). Periodic abstinence (e.g., calendar ovulation, symptothermal, post ovulation methods), the rhythm method, and the withdrawal method are not acceptable methods of contraception. Female subjects must not donate ova, or retrieve for their own use, from the time of screening and throughout the study treatment period, and for at least 7 months after the last dose of study treatment. They should refrain from breastfeeding throughout this time. Preservation of ova may be considered prior to randomization in this study.

14. Non-sterilized male subjects who are sexually active with a female partner of childbearing potential must use a condom with spermicide from screening and throughout the duration of the study treatment and the washout period (4 months after the last dose of DB-1303, 6 months after the last dose of paclitaxel or nab-paclitaxel, and 3 months after the last dose of capecitabine). Abstinence is acceptable only as true abstinence when this is in line with the preferred and usual lifestyle of the subject for the duration of the study treatment and the drug washout period. Periodic abstinence (e.g., calendar ovulation, symptothermal, post ovulation methods), the rhythm method, and the withdrawal method are not acceptable methods of contraception. It is strongly recommended for the female partners of a male subject also use at least one highly effective method of contraception throughout this period. In addition, male subjects should refrain from fathering a child or donating sperm throughout the duration of the study and the washout period (4 months after the last dose of DB-1303, 6 months after the last dose of paclitaxel or nab paclitaxel, and 3 months after the last dose of capecitabine). Preservation of sperm should be considered prior to randomization in this study.

15. Must be able and willing to comply with the protocol requirements and must sign and date the informed consent form prior to any screening evaluations.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Ineligible for all options in the investigator's choice chemotherapy arm.
2. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, uncontrolled or significant cardiovascular disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring adverse events or compromise the ability of the subject to give written informed consent.
3. Clinically uncontrolled pleural effusion, ascites or pericardial effusion requiring repeated drainage, peritoneal shunt or cell-free concentrated ascites reinfusion therapy within 2 weeks prior to the randomization.
4. Uncontrolled or significant cardiovascular disease
5. Has a medical history of interstitial lung diseases (e.g., non-infectious interstitial pneumonia, pneumonitis, pulmonary fibrosis, and radiation pneumonitis which needs glucocorticoids and antibiotics) or current interstitial lung diseases or who are suspected to have these diseases by imaging at screening.
6. Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade = 1 or baseline or Grade = 2 anemia.
7. Previous treatment with anti-HER2 therapy.
8. Prior treatment with antibody-drug conjugate that comprised an exatecan derivative that is a topoisomerase I inhibitor.
9. Prior randomization or treatment in a previous DB-1303/BNT323 study regardless of treatment assignment.
10. Has substance abuse or any other medical conditions such as psychological conditions, that may, in the opinion of the Investigator, interfere with the subject's participation in the clinical study or evaluation of the clinical study results.
11. Individuals who are dependent on the Sponsor, clinical site, or Investigator (e.g., is an employee of the Sponsor or the clinical trial site, a dependent of the Investigator, or any site staff member otherwise supervised by the Investigator).
12. Individuals who are committed to an institution by virtue of an order issued either by the judicial or the administrative authorities, in accordance with local regulations.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
18/01/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/05/2028
Actual
Sample size
Target
532
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Research Site 6108-0 - Camperdown
Recruitment hospital [2] 0 0
Research Site 6109-0 - Liverpool
Recruitment hospital [3] 0 0
Research Site 6102-0 - Sydney
Recruitment hospital [4] 0 0
Research Site 6106-0 - Birtinya
Recruitment hospital [5] 0 0
Research Site 6101-0 - South Brisbane
Recruitment hospital [6] 0 0
Research Site 6107-0 - Southport
Recruitment hospital [7] 0 0
Research Site 6104-0 - Townsville
Recruitment hospital [8] 0 0
Research Site 6110-0 - Adelaide
Recruitment hospital [9] 0 0
Research Site 6103-0 - Bendigo
Recruitment hospital [10] 0 0
Research Site 6105-0 - St. Albans
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2170 - Liverpool
Recruitment postcode(s) [3] 0 0
2109 - Sydney
Recruitment postcode(s) [4] 0 0
4575 - Birtinya
Recruitment postcode(s) [5] 0 0
4101 - South Brisbane
Recruitment postcode(s) [6] 0 0
4215 - Southport
Recruitment postcode(s) [7] 0 0
4814 - Townsville
Recruitment postcode(s) [8] 0 0
2155 - Adelaide
Recruitment postcode(s) [9] 0 0
3550 - Bendigo
Recruitment postcode(s) [10] 0 0
3021 - St. Albans
Recruitment outside Australia
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United States of America
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Arizona
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California
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Colorado
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Florida
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United States of America
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Georgia
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Illinois
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Kansas
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Kentucky
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Maryland
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Missouri
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Oregon
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Santa Fe
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Gyor
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Bergamo
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Italy
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Brescia
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Italy
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Catania
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Italy
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Catanzaro
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Milano
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Italy
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Napoli
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Italy
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Verona
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Korea, Republic of
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Gangwon-do
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Korea, Republic of
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Gyeonggi-do
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Korea, Republic of
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Busan
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Korea, Republic of
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Incheon
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Seoul
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Poland
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Rzeszów
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Poland
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Torun
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Lódz
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Barcelona
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Sevilla
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Spain
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Valencia
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United Kingdom
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Cornwall
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United Kingdom
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Greater London
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United Kingdom
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Greater Manchester
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West Yorkshire
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United Kingdom
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Nottingham

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
DualityBio Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
BioNTech SE
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Lily Hu
Address 0 0
DualityBio Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Helen Liu
Address 0 0
Country 0 0
Phone 0 0
86-21-26018730
Fax 0 0
Email 0 0
helen.liu@dualitybiologics.com
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT06018337