⁃ 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:

• Is advanced or metastatic

• 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).

⁃ 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:

• 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

• 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 (β-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.