Breast Cancer
Conditions
Interventions
Arm 1: Dato-DXd
Experimental: Dato-DXd
Experimental drug. Provided in 100mg vials. IV infusion.
Other Name: Datopotamab deruxtecan (Dato-DXd, DS-1062a)
Arm 2: ICC
Active Comparator: Investigators Cho
Sponsors
Inoguchi Akihiro
AstraZeneca
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Age 1. Participant must be >= 18 years Type of Participant and Disease Characteristics 2. Inoperable or metastatic HR-positive, HER2-negative breast cancer (per ASCO/CAP guidelines, on local laboratory results); ie, is documented as HR-positive (either ER and/or PgR positive [ER or PgR >= 1%]) and HER2-negative. If a participant had multiple results after metastatic disease, the most recent local test result will be used to confirm eligibility. 3. Progressed on or not suitable for endocrine therapy per investigator assessment, and treated with 1 to 2 lines of prior standard of care chemotherapy in the inoperable/metastatic setting. Participant must have documented progression on their most recent line of chemotherapy. Note: If a chemotherapy drug is changed within 28 days of use to another drug in the same class (ie, antimetabolite to antimetabolite) for any reason, the first drug is not counted as a line. Targeted agents (such as mTOR inhibitors, PD-1/PD-L1 inhibitors, PARP inhibitors), endocrine therapies, and CDK4/6 inhibitors on their own do not contribute to the count of prior lines of chemotherapy; however, regimens with such agents in combination with metastatic chemotherapy should be classified as one line of chemotherapy. 4. Eligible for one of the chemotherapy options listed as ICC (eribulin, capecitabine, vinorelbine, gemcitabine), per investigator assessment. Note: Participants who previously received any of these agents are eligible for enrolment to another ICC agent in this study. 5. ECOG PS of 0 or 1, with no deterioration over the previous 2 weeks prior to day of first dosing. 6. At least 1 measurable lesion not previously irradiated that qualifies as a RECIST 1.1. Target Lesion at baseline and can be accurately measured at baseline as >= 10 mm in the longest diameter (except lymph nodes, which must have short axis >= 15 mm) with CT or MRI, which is suitable for accurate repeated measurements. Note: Participants with bone-only metastases are not permitted. 7. Participants with a history of previously treated neoplastic spinal cord compression, or clinically inactive brain metastases, who require no treatment with corticosteroids or anticonvulsants, may be included in the study, if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of radiotherapy and study enrolment. 8. Adequate organ and bone marrow function within 7 days before day of first dosing as follows: - Hemoglobin: >= 9.0 g/dL. Red blood cell/plasma transfusion is not permitted within 1 week prior to screening assessment. - Absolute neutrophil count:>= 1500/mm^3 . Granulocyte colony-stimulating factor administration is not permitted within 1 week prior to screening assessment. - Platelet count: >= 100000/mm^3. Platelet transfusion is not permitted within 1 week prior to screening assessment. - Total bilirubin: = 30 mL/min as calculated using the Cockcroft- Gault equation (using actual body weight): Female: CrCl = Weight (kg) x (140 - Age) x 0.85 (mL/min) 72 x serum creatinine (mg/dL) Male: CrCl = Weight (kg) x (140 - Age) (mL/min) 72 x serum creatinine (mg/dL) 9. LVEF >= 50%
Exclusion criteria
Exclusion criteria: 1. As judged by the investigator, any evidence of diseases (such as severe or uncontrolled systemic diseases, uncontrolled hypertension, history of allogeneic organ transplant, and active bleeding diseases, ongoing or active infection, or significant or cardiac or psychological conditions) which, in the investigator's opinion, makes it undesirable for the participant to participate in the study or that would jeopardize compliance with the protocol. 2. History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 3 years before the first dose of study intervention and of low potential risk for recurrence. Exceptions include basal cell carcinoma of the skin and squamous cell carcinoma of the skin that has undergone potentially curative therapy, adequately resected non-melanoma skin cancer, curatively treated in situ disease, or other solid tumors curatively treated. 3. Persistent toxicities caused by previous anticancer therapy (excluding alopecia), not yet improved to CTCAE Version 5.0 Grade Grade 2 for at least 3 months prior to first dosing and managed with SoC treatment) which the investigator deems related to previous anticancer therapy, including (but not limited to): - Chemotherapy-induced neuropathy. - Fatigue. - Residual toxicities from prior immunotherapy treatment: Grade 1 or Grade 2 endocrinopathies which may include: o Hypothyroidism/hyperthyroidism. o Type I diabetes. o Hyperglycaemia. o Adrenal insufficiency o Adrenalitis. - Skin hypopigmentation (vitiligo). 4. Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals; suspected infections (eg, prodromal symptoms); or inability to rule out infections. Note: Participants with localized fungal infections of skin or nails are eligible. 5. Known active or uncontrolled hepatitis B or C infection. Participants are eligible if they: a. Have been curatively treated for HCV infection as demonstrated clinically and by viral serologies b. Have received HBV vaccination with only anti-HBs positivity and no clinical signs of hepatitis c. Are HBsAg- and anti-HBc+ (i.e., those who have cleared HBV after infection) and meet conditions i-iii below: d. Are HBsAg+ with chronic HBV infection (lasting 6 months or longer) and meet conditions i-iii below: i. HBV DNA viral load 350 cells/mm3, no history of AIDs-defining opportunistic infection within the past 12 months, and stable for at least 4 weeks on same anti-HIV retroviral medications (meaning there are no expected further changes in that time to the number or type of antiretroviral drugs in the regimen). If an HIV infection meets the above criteria, monitoring of viral RNA load and CD4+ count is recommended. Participants must be tested for HIV if acceptable by local regulations or an IRB/EC. 7. Uncontrolled or significant cardiac disease, including myocardial infarction or uncon
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Progression-Free Survival [Time Frame: On-study tumor assessments occur every 6 weeks then every 9 weeks until disease progression, death or withdrawal of consent assessed up to data cut-off (17Jul2023) to a maximum of approximately 21 months] PFS is defined as time from randomization until progression per RECIST 1.1, as assessed by BICR, or death due to any cause. The analysis will include all randomized participants as randomized regardless of whether the participant withdraws from therapy, receives another anti-cancer therapy, or clinically progresses prior to RECIST 1.1. 2. Overall Survival [Time Frame: From date of randomization until death due to any cause. Assessed up to data cut-off (24Jul2024) to a maximum of approximately 33 months] OS is defined as time from randomization until the date of death due to any cause. The comparison will include all randomized participants as randomized, regardless of whether the participant withdraws from therapy or receives another anti-cancer therapy. The measure of interest is the hazard ratio of OS. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Objective Response Rate (ORR) [Time Frame: From date of randomization until event. Assessed up to data cut-off (17Jul2023) to a maximum of approximately 21 months for BICR assessment and assessed up to data cut-off (24Jul2024) to a maximum of approximately 33 months for investigator assessment] Objective response rate is defined as the proportion of participants who have a confirmed CR or PR, as determined by the BICR/Investigator assessment, per RECIST 1.1. 2. Duration of Response (DoR) as Assessed by BICR Assessment [Time Frame: From date of first response until progression or death. Tumor assessments occur every 6 weeks then every 9 weeks until disease progression, death or withdrawal of consent. Assessed up to data cut-off (17Jul2023) to a maximum of approximately 21 months] Duration of response is defined as the time from the date of first documented confirmed response until date of documented progression per RECIST 1.1, as assessed by BICR assessment or death due to any cause. 3. Duration of Response (DoR) as Assessed by Investigator Assessment [Time Frame: From date of first response until progression or death. Tumor assessments occur every 6 weeks then every 9 weeks until disease progression, death or withdrawal of consent. Assessed up to data cut-off (24Jul2024) to a maximum of approximately 33 months] Duration of response is defined as the time from the date of first documented confirmed response until date of documented progression per RECIST 1.1, as assessed by Investigator assessment or death due to any cause. 4. Progression-Free Survival by Investigator Assessment [Time Frame: On-study tumor assessments occur every 6 weeks then every 9 weeks until disease progression, death or withdrawal of consent assessed up to data cut-off (24Jul2024) to a maximum of approximately 33 months] PFS by Investigator assessment will be defined as the time from the date of randomization until the date of PD per RECIST 1.1 (by Investigator assessment) or death (by any | — |
Countries
Argentina, Belgium, Brazil, Canada, China, France, Germany, Hungary, India, Italy, Japan, Korea, Mexico, Netherlands, Poland, Russia, South Africa, Spain, Taiwan, United Kingdom, United States
Contacts
Public ContactContact for Clinical Trial Information
DAIICHI SANKYO Co.,Ltd.
Outcome results
None listed