Inoperable or Metastatic Hormone Receptor-Positive, HER2-Negative Breast Cancer that Have Been Treated With One or Two Prior Lines of Systemic Chemotherapy MedDRA version: 23.0 Level: PT Classification code 10083232 Term: HER2 negative breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Datopotamab deruxtecan
Product Code: DS-1062a
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: Datopotamab deruxtecan
CAS Number: 2238831-60-0
C
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Participant must be = 18 years (= 20 years in Japan) at the time of screening. 2. Inoperable or metastatic HR+, HER2-negative breast cancer 3. Progressed on or not suitable for endocrine therapy per investigator assessment, and treated with 1 to 2 lines of prior chemotherapy in the inoperable/metastatic setting. 4. Eligible for one of the chemotherapy options listed as ICC (eribulin, capecitabine, vinorelbine, gemcitabine), per investigator assessment. 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. 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/L. - Absolute neutrophil count: 1500/mm3. - Platelet count: 100000/mm3. - Total bilirubin: = 1.5 × ULN if no liver metastases; or = 3 × ULN in the presence of documented Gilbert’s syndrome (unconjugated hyperbilirubinemia) or liver metastases at baseline. - ALT and AST: = 2.5 × ULN for AST/ALT; however, if elevation is due to liver metastases, = 5.0 × ULN is allowed. - Calculated creatinine clearance: = 30 mL/min as calculated using the Cockcroft-Gault equation (using actual body weight). 9. LVEF = 50% by either an echocardiogram or MUGA within 28 days of first dosing. 10. Has had an adequate treatment washout period before Cycle 1 Day 1, defined as: - Major surgery: = 3 weeks. - Radiation therapy including palliative radiation to chest: = 4 weeks (palliative radiation therapy to other areas = 2 weeks). - Anticancer therapy including hormonal therapy: = 3 weeks (for small molecule targeted agents: = 2 weeks or 5 half-lives, which ever is longer) - Antibody-based anticancer therapy: = 4 weeks with the exception of receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitors - Chloroquine/hydroxychloroquine: = 14 days. 11. Have available a FFPE tumor sample (block preferred, or a minimum of 20 freshly cut slides), at the time of screening. Note: Sample collection in China will comply with local regulatory approval. 12. Minimum life expectancy of 12 weeks at screening. 13. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies; (estrogens are not permitted). 14. Negative pregnancy test (urine and/or serum) for women of childbearing potential 15. Female participants must be post-menopausal for at least 1 year, surgically sterile, or using one highly effective form of birth control. Female participants must refrain from egg cell donation and breastfeeding while on study and for at least 7 months after the last dose of study intervention. Non-sterilized male partners of a woman of childbearing potential must use a male condom plus spermicide throughout this period. 16. Male participants who intend to be sexually active with a female partner of childbearing potential must be surgically sterile or using an acceptable method of
Exclusion criteria
Exclusion criteria: 1. Any evidence of diseases 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. 3. Persistent toxicities caused by previous anticancer therapy (excluding alopecia), not yet resolved to CTCAE Version 5.0 Grade = 1 or baseline. 4. Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals; suspected infections (eg, prodromal symptoms); or inability to rule out infections. 5. Known active or uncontrolled hepatitis B or C infection; or positive for hepatitis B or C virus based on the evaluation of results of tests for hepatitis B (HBsAg, anti-HBs, anti-HBc, or HBV DNA) or hepatitis C (HCV antibody or HCV RNA) infection at screening. 6. Known HIV infection that is not well controlled. 7. Uncontrolled or significant cardiac disease, including myocardial infarction or uncontrolled/unstable angina within 6 months prior to C1D1, CHF (New York Heart Association Class II to IV), uncontrolled or significant cardiac arrhythmia, or uncontrolled hypertension (resting systolic blood pressure > 180 mmHg or diastolic blood pressure > 110 mmHg). 8. Investigator judgment of 1 or more of the following: - Mean resting corrected QTcF interval > 470 ms - History of QT prolongation associated with other medications that required discontinuation of that medication, or any current concomitant medication known to prolong the QT interval and cause Torsades de Pointes. - Congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives. 9. 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. 10. Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder, or any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement, or prior pneumonectomy. 11. Leptomeningeal carcinomatosis. 12. Clinically significant corneal disease. 13. Known active tuberculosis infection 14. Any of the following prior anticancer therapies: - Any treatment (including ADC) containing a chemotherapeutic agent targeting topoisomerase I - - TROP2-targeted therapy - Prior treatment with same ICC agent 15. Any concurrent anticancer treatment, with the exception of bisphosphonates, denosumab, for the treatment of bone metastases. 16. Concurrent use of hormonal therapy for non-cancer-related conditions. 17. Major surgical procedure (excluding placement of vascular access) or significant traumatic injury within 3 weeks of the first dose of study intervention or an anticipated need for major surgery during the study. 18. Receipt of live, attenuated vaccine within 30 days prior to the first dose of study treatment. 19. Concomitant use of chronic systemic (IV or oral) corticosteroids or other immunosuppressive medications except for managing adverse events (inhaled steroids or intra articular steroid injections are permitted in this study). 20. Previous treatment in the present study. 21. Participation in another clinical study with a study intervent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Dual Primary: 1. To demonstrate the superiority of Dato-DXd compared to ICC by assessment of PFS in participants with inoperable or metastatic HR-positive,HER2-negative breast cancer, who have been treated with 1 or 2 lines of chemotherapy in the inoperable/metastatic setting, per BICR. 2. To demonstrate the superiority of Dato-DXd compared to ICC by assessment of OS in participants with inoperable or metastatic HR-positive,HER2-negative breast cancer, who have been treated with 1 or 2 lines of chemotherapy in the inoperable/metastatic setting.;Secondary Objective: 1. To demonstrate the superiority of Dato-DXd compared to ICC by assessment of ORR. 2. To demonstrate the superiority of Dato-DXd compared to ICC by assessment of DoR. 3. To demonstrate the superiority of Dato-DXd compared to ICC by assessment of PFS. 4. To demonstrate the superiority of Dato-DXd compared to ICC by assessment of DCR. 5. To assess pain in participants treated with Dato-DXd compared to ICC. 6. To assess physical functioning. 7. To assess global health status/quality of life (GHS/QoL). 8. To demonstrate the superiority of Dato-DXd compared to ICC by assessment of TFST. 9. To demonstrate the superiority of Dato-DXd compared to ICC by assessment of TSST. 10. To demonstrate the superiority of Dato-DXd compared to ICC by assessment of PFS2. 11. To assess the PK of Dato-DXd 6mg/kg IV Q3W. 12. To investigate the immunogenicity of Dato-DXd 6mg/kg IV Q3W.;Primary end point(s): 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. The measure of interest is the hazard ratio of PFS. OS is defined as time from randomization until the date of death due to any cause. The comparison will include all randomi | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Objective Response Rate: 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: 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/Investigator assessment or death due to any cause. 3. Progression-Free Survival by Investigator assessment: 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 cause in the absence of progression), (ie, date of event or censoring – date of randomization + 1). 4. Disease Control Rate: Disease control rate at 12 weeks is defined as the percentage of participants who have a confirmed CR or PR or who have SD, per RECIST 1.1, as assessed BICR/per investigator assessment and derived from the raw tumor data for at least 11 weeks after randomization. 5. Time to First Subsequent Therapy (TFST): Time to first subsequent therapy is defined as the time from randomization until the start date of the first subsequent anti-cancer therapy after discontinuation of randomized treatment, or death due to any cause. 6. Time to Second Subsequent Therapy (TSST): Time to second subsequent therapy is defined as the time from randomization to until the start date of the second subsequent anti-cancer therapy after discontinuation of first subsequent treatment, or death due to any cause. 7. Time from randomization to second progression or death (PFS2): Time to second progression of death will be defined as the time from the randomization to the earliest of the progression event (following the initial progression), subsequent to first subsequent therapy, or death. The date of second progression will be recorded by the Investigator in the eCRF and defined according to loc | — |
Countries
Argentina, Belgium, Brazil, Canada, China, France, Germany, Hungary, India, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Poland, Russian Federation, South Africa, Spain, Taiwan, United Kingdom, United States
Contacts
Public ContactUnidad de Investigación Clínica
AstraZeneca Farmacéutica Spain, S.A.
Outcome results
None listed