A Phase 3 Study of DB-1303 vs Investigator's Choice Chemotherapy in HER2-low, Hormone Receptor Positive, Metastatic Breast Cancer
- Conditions
- HER2-low, Hormone Receptor Positive, Metastatic Breast Cancer, HER2-low, Hormone Receptor Positive, Metastatic Breast CancerMedDRA version: 23.0Level: LLTClassification code: 10070575Term: Estrogen receptor positive breast cancer Class: 10029104MedDRA version: 23.0Level: PTClassification code: 10083232Term: HER2 negative breast cancer Class: 100000004864Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2023-507333-17-00
- Lead Sponsor
- Dualitybio Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 532
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), Adequate organ and bone marrow function within 14 days before randomization., Has adequate treatment washout period before randomization, as defined in the protocol., 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., 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 (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)., Pathologically documented breast cancer that: 1) Is advanced or metastatic 2) Has HER2low expression (IHC 1+ or IHC 2+/ISH-) 3) Was never previously reported as HER2-positive (IHC 3+ or ISH+) as per ASCO/CAP guidelines. 4) Is documented as HR+ (either ER and/or 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., ECOG 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, mTOR or 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 CT or 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., Has LVEF = 50% by either echocardiography (ECHO) or multiple-gated acquisition (MUGA) within 28 days before randomization.
Ineligible for all options in the investigator’s choice chemotherapy arm. Subjects with contraindications to capecitabine, paclitaxel, and nab-paclitaxel treatment, per local prescribing information, cannot be enrolled to the study., Active primary immunodeficiency, known human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection. Subjects should be tested for HIV prior to randomization if required by local regulations or by the institutional review board (IRB)/independent ethics committee (IEC), Receipt of live, attenuated vaccine (mRNA and replication-deficient adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first dose of study treatment. Note: Subjects, if enrolled, should not receive live vaccine during the study and up to 30 days after the last dose of study treatment., Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade = 1 or baseline., Pregnant or breastfeeding female subjects, or subjects who are planning to become pregnant., Subjects with a known hypersensitivity to either the drug substances, inactive ingredients in the drug product or to other monoclonal antibodies., History of another primary malignancy within 3 years, except adequately resected non melanoma skin cancer, curatively treated in situ disease, other solid tumors curatively treated, or contralateral breast cancer., 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 study regardless of treatment assignment, Participation in another clinical study with a study treatment administered in the last 30 days or if the washout period is less than five half-lives prior to first dose of study treatment or concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow up period of an interventional study. Of note, tissue screening for this study while a subject is on treatment in another clinical study is acceptable., Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, uncontrolled or significant cardiovascular disease, serious chronic gastrointestinal conditions associated with diarrhoea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the subject to give written informed consent., 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., 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) 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 d
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method