trastuzumab deruxtecan (t-dxd) in patients who have hormone receptor-negative and hormone receptor-positive her2-low or her2 ihc 0 metastatic breast cancer

Conditions: Breast Cancer

Summary: this study will evaluate the safety and efficacy of trastuzumab deruxtecan (t-dxd) in participants with human epidermal growth factor receptor 2 (her2)-low or her2 immunohistochemistry (ihc) 0 (who are both hormone receptor \[hr\]-negative and hr-positive) unresectable and/or metastatic breast cancer.

the primary endpoint of interest in this study is time to next treatment (ttnt), a measure that will determine how long t-dxd allows patients to derive clinical benefit from the study drug.

Eligibility criteria:
inclusion criteria: * sign and date the main informed consent form * must agree to provide a newly obtained or archival baseline biopsy from primary and/or metastatic lesion. * pathologically documented breast cancer (bc) tumor * is unresectable and/or metastatic. * is hormone receptor-negative or hormone receptor-positive. * must include percentage of positively stained cells to characterize if hormone receptor-positive or -negative. * has confirmed her2 ihc 1+ or ihc 2+/ish- (her2-low) status or her2 ihc 0 status as determined according to asco cap 2018 guidelines1 based on sample collected during tissue screening as described above. * was never previously her2-positive (ihc 3+ or ihc 2+/ish+) on prior pathology testing (per asco cap guidelines). * was never previously treated with anti-her2 therapy in the metastatic setting. * has had at least one and up to two prior lines of therapy in the metastatic setting. * in participants with hormone receptor-positive her2-low metastatic bc (cohort 3): * has recurrent disease \<2 years from the initiation of adjuvant et or * has disease progression on cdk4/6 inhibitor-based regimen within 12 months of completion of adjuvant therapy with a cdk4/6 inhibitor or * has disease progression within the first 12 months of cdk4/6 in the first line metastatic setting * presence of at least one measurable lesion based on computed tomography or magnetic resonance imaging. * participants with brain metastases are allowed in the study. the brain lesion(s) should be small (\<2 cm), untreated, asymptomatic, not requiring urgent medical intervention, and are asymptomatic and clinically stable. * has an eastern cooperative oncology group performance status of 0 or 1. * has a minimum life expectancy of 12 weeks at screening. * has a left ventricular ejection fraction ≥50% within 28 days before enrollment. * has adequate organ and bone marrow function within 28 days before enrollment. * has adequate treatment washout period before enrollment. * male and female subjects of reproductive/childbearing potential must agree to use a highly effective form of contraception. exclusion criteria: * prior treatment with an antibody drug conjugate (adc). * uncontrolled or significant cardiovascular disease. * has a corrected qt interval prolongation. * has 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. * has spinal cord compression or clinically active central nervous system metastases. * has multiple primary malignancies within 3 years, except adequately resected non-melanoma skin cancer, curatively treated in situ disease, other solid tumors curatively treated, or contralateral bc. * has a history of severe hypersensitivity reactions to either the drug substances or inactive ingredients in the drug product. * has a history of severe hypersensitivity reactions to other monoclonal antibodies. * has an uncontrolled infection requiring intravenous (iv) antibiotics, antivirals, or antifungals. * active primary immunodeficiency, known uncontrolled active human immunodeficiency virus (hiv) infection, or active hepatitis b or c infection. * has history of receiving a live, attenuated vaccine (messenger rna and replication-deficient adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first exposure to study drug. * has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to grade ≤1 or baseline. * is pregnant or breastfeeding or planning to become pregnant. * lung-specific intercurrent clinically significant illnesses. * any autoimmune, connective tissue, or inflammatory disorders. * prior complete pneumonectomy.

Keywords: trastuzumab derextecan enhertu® ds8201-a breast cancer anti-her2-antibody drug conjugate