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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT06018337




Registration number
NCT06018337
Ethics application status
Date submitted
25/08/2023
Date registered
30/08/2023
Date last updated
6/06/2024

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 doseof 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 doseof 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, preferably in formalin fixation and paraffin embedding (FFPE) blocks based on a
mandatory FFPE tumor sample 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 or have
non-measurable, bone-only disease that can be assessed by computer tomography (CT) or
Magnetic Resonance Imaging (MRI) or X-Ray. Lytic or mixed lytic bone lesions that can be
assessed by CT or MRI or X-Ray in the absence of measurable disease as defined above is
acceptable; subjects with sclerotic/osteoblastic bone lesions only in the absence of
measurable disease are not eligible.

9. 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.

10. 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
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
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 as a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that
required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis
cannot be ruled out by imaging at screening.

6. Subjects with prior use of immunosuppressive medication within 14 days prior to first
study dose, except for intranasal and inhaled corticosteroids or systemic
corticosteroids at doses less than 10 mg/day of prednisone or equivalent.

7. Has unresolved toxicities from previous anticancer therapy, defined as toxicities
(other than alopecia) not yet resolved to Grade = 1 or baseline.

8. Previous treatment with anti-HER2 therapy.

9. Prior treatment with antibody-drug conjugate that comprised an exatecan derivative
that is a topoisomerase I inhibitor.

10. Prior randomization or treatment in a previous DB-1303/BNT323 study regardless of
treatment assignment.

11. 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.

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)
SA
Recruitment hospital [1] 0 0
Research Site - Adelaide
Recruitment postcode(s) [1] 0 0
2155 - Adelaide
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Illinois
Country [3] 0 0
United States of America
State/province [3] 0 0
Pennsylvania
Country [4] 0 0
United States of America
State/province [4] 0 0
Texas
Country [5] 0 0
United States of America
State/province [5] 0 0
Virginia
Country [6] 0 0
China
State/province [6] 0 0
Anhui
Country [7] 0 0
China
State/province [7] 0 0
Beijing
Country [8] 0 0
China
State/province [8] 0 0
Fujian
Country [9] 0 0
China
State/province [9] 0 0
Gansu
Country [10] 0 0
China
State/province [10] 0 0
Guangdong
Country [11] 0 0
China
State/province [11] 0 0
Guangxi
Country [12] 0 0
China
State/province [12] 0 0
Hebei
Country [13] 0 0
China
State/province [13] 0 0
Heilongjiang
Country [14] 0 0
China
State/province [14] 0 0
Henan
Country [15] 0 0
China
State/province [15] 0 0
Hubei
Country [16] 0 0
China
State/province [16] 0 0
Hunan
Country [17] 0 0
China
State/province [17] 0 0
Jiangsu
Country [18] 0 0
China
State/province [18] 0 0
Jiangxi
Country [19] 0 0
China
State/province [19] 0 0
Jilin
Country [20] 0 0
China
State/province [20] 0 0
Liaoning
Country [21] 0 0
China
State/province [21] 0 0
Shandong
Country [22] 0 0
China
State/province [22] 0 0
Shanghai
Country [23] 0 0
China
State/province [23] 0 0
Shanxi
Country [24] 0 0
China
State/province [24] 0 0
Sichuan
Country [25] 0 0
China
State/province [25] 0 0
Tianjin
Country [26] 0 0
China
State/province [26] 0 0
Yunnan
Country [27] 0 0
China
State/province [27] 0 0
Zhejiang
Country [28] 0 0
France
State/province [28] 0 0
Gard
Country [29] 0 0
France
State/province [29] 0 0
Val De Marne

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
The goal of this clinical trial is to assess the efficacy of DB-1303/BNT323 compared with
investigator's choice chemotherapy in terms of progression-free survival (PFS) by blinded
independent central review (BICR) in the HR+, HER2-low (immunohistochemistry [IHC]2+/in situ
hybridization [ISH]- and IHC 1+) population.
Trial website
https://clinicaltrials.gov/ct2/show/NCT06018337
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Diana Chen
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT06018337