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A Study of DB-1303/BNT323 vs Investigator's Choice Chemotherapy in HER2-Low, Hormone Receptor Positive Metastatic Breast Cancer (DYNASTY-Breast02)

PHASE3RECRUITING

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.

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Study details:

The study is a Phase III, Randomized, Multi-center, Open-label study in HER2-low, HR+ metastatic breast cancer subjects whose disease has progressed on at least 2 lines of prior ET or within 6 months of first line ET + Cyclin-dependent kinase (CDK) 4/6 inhibitor in the metastatic setting. The primary purpose of the study is to determine the efficacy and safety of DB-1303/BNT323 compared with investigator's choice single agent chemotherapy in the target population. Approximately 532 subjects with HER2 IHC 2+/ISH- and IHC 1+ (HER2-low\] expression will be randomized 1:1 across approximately 230 centers globally to receive either DB-1303 or investigator's choice single agent chemotherapy (capecitabine, paclitaxel or nab-paclitaxel) until Response Evaluation Criteria in Solid Tumors (RECIST) 1.

1 defined disease progression (PD), unless there is unacceptable toxicity, withdrawal of consent, or another criterion for discontinuation is met.

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Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

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).

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.

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.

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).

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;

Eastern Cooperative Oncology Group performance status of 0 or 1.

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.

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.

Life expectancy ≥12 weeks at screening.

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.

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.

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.

Exclusion criteria

Ineligible for all options in the investigator's choice chemotherapy arm.

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.

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.

Uncontrolled or significant cardiovascular disease

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.

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.

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

Previous treatment with anti-HER2 therapy.

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

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

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.

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Eligibility

Age eligible for study : 18 and older

Healthy volunteers accepted : No

Gender eligible for study: All

Things to know

Study dates

Study start: 2024-01-18

Primary completion: 2025-12-01

Study completion finish: 2028-05-01

Study type

TREATMENT

Phase

PHASE3

Trial ID

NCT06018337

Intervention or treatment

DRUG: DB-1303/BNT323

DRUG: Capecitabine

DRUG: Paclitaxel

DRUG: Nab-paclitaxel

Conditions

• Metastatic Breast Cancer

Image related to Metastatic Breast Cancer

Condition: Metastatic Breast Cancer
DRUG: DB-1303/BNT323 and other drugs
South Brisbane, Queensland, Australia
Sponsor: DualityBio Inc.

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Find a site

Closest Location:

Research Site

Research sites nearby

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Research Site
South Brisbane, Queensland, Australia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/Arm	Intervention/Treatment
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	DRUG: DB-1303/BNT323 IV
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.	DRUG: Capecitabine Oral

Participant Group/Arm

Intervention/Treatment

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

DRUG: DB-1303/BNT323

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.

DRUG: Capecitabine

Oral

What is the study measuring?

Primary outcome

Primary Outcome Measure	Primary Outcome Description	Primary Outcome Time Frame
Progression-free survival (PFS) in the HR+, HER2-low population	PFS by BICR according to RECIST 1.1 in the HR+, HER2-low population	Up to approximately 51 months

Secondary outcome

Secondary Outcome Measure	Secondary Outcome Description	Secondary Outcome Time Frame
Overall survival (OS) in the HR+, HER2-low population	OS in the HR+, HER2-low population	Up to approximately 51 months
Objective response rate (ORR) in the HR+, HER2-low population	ORR by BICR and Investigator assessment according to RECIST 1.1 in the HR+, HER2-low population	Up to approximately 51 months
PFS by Investigator assessment	PFS by Investigator assessment according to RECIST 1.1 in the HR+, HER2-low population	Up to approximately 51 months
Duration of response (DoR) in the HR+, HER2-low population	DoR by BICR and Investigator assessment according to RECIST 1.1 in the HR+, HER2-low population	Up to approximately 51 months
Treatment-emergent adverse events (TEAEs)	TEAEs per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0	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
Serious adverse events (SAEs)	SAEs per NCI CTCAE v5.0	from the time of the subject signing the ICF until the follow-up period is completed (35 days after the last doseof study treatment
Patient reported outcomes (PROs): European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) - C30	Change from baseline in the functioning/symptom/global quality of life (QoL) subscales of EORTC QLQ-C30. Scale scores range from 0-100. For functioning and global QoL scales, higher scores indicate better functioning or global health status. For symptom scales, higher scores indicate greater symptom burden.	Up to approximately 51 months
Patient reported outcomes (PROs): EORTC QLQ-BR45	Change from baseline in the functioning/symptom subscales of EORTC QLQ-BR45. Scale scores range from 0-100. For functioning scales, higher scores indicate better functioning. For symptom scales, higher scores indicate greater symptom burden.	Up to approximately 51 months
Patient reported outcomes (PROs): European Quality of Life Five Dimension Five Level Scale (EQ-5D-5L)	Change from baseline in EQ-5D-5L health state utility index score and Visual Analogue Scale (VAS) score. VAS score range from 0-100, higher scores indicate better health status.	Up to approximately 51 months
European Quality of Life Five Dimension Five Level Scale (EQ-5D-5L)	EQ-5D-5L health state utility index score and Visual Analogue Scale (VAS) score. The change from baseline value will be reported.	Up to approximately 51 months

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References

Clinical Trials Gov: A Study of DB-1303/BNT323 vs Investigator's Choice Chemotherapy in HER2-Low, Hormone Receptor Positive Metastatic Breast Cancer (DYNASTY-Breast02)