Inoperable or Metastatic Hormone Receptor-Positive, HER2-Negative Breast Cancer that Have Been Treated With One or Two Prior Lines of Systemic Chemotherapy
Conditions
Interventions
Trade Name: na
Product Name: Datopotamab deruxtecan
Product Code: [DS-1062a]
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: Datopotamab deruxtecan
CAS Numbe
Sponsors
ASTRAZENECA AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1 Partic must be = 18 years (= 20 years in Japan) at the time of screening 2 Inoper or metastatic HR+, HER2-negative breast cancer 3 Progr on or not suitable for endocrine ther per investigator assessment, and treated with 1 to 2 lines of prior chemo in the inoperable/metastatic setting 4 Eligible for one of the chemo 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 wks prior to day of first dosing 6 At least 1 measurable lesion not previously irradiated that qualifies as a RECIST 11 Note: Partics with bone-only metastases are not permitted 7 Partics with a history of previously treated neoplastic spinal cord compression, or clinically inactive brain metastases, who require no treat with corticosteroids or anticonvulsants, may be included in the st, if they have recovered from the acute toxic effect of radiother A minimum of 2 wks must have elapsed between the end of radiother and st enrolment 8 Adequate organ and bone marrow function within 7 ds before day of first dosing as follows: - Hb: = 90 g/L - Absolute neutrophil count: 1500/mm3 - Platelet count: 100000/mm3 - Total bilir: = 15 × ULN if no liver metastases; or = 3 × ULN in the presence of documented Gilbert’s syndr (unconjugated hyperbilirubinemia) or liver metastases at baseline - ALT and AST: = 25 × ULN for AST/ALT; however, if elevation is due to liver metastases, = 50 × ULN is allowed - Calc creat clear: = 30 mL/min as calculated using the Cockcroft-Gault equation (using actual body weight) 9 LVEF = 50% by either an ecg or MUGA within 28 ds of first dosing 10 Has had an adequate treat washout period before Cycle 1 Day 1, defined as: - Major surgery: = 3 wks - Rad ther including palliative rad to chest: = 4 wks (palliative rad ther to other areas = 2 wks) - Anticancer ther including hormonal ther: = 3 wks (for small molecule targeted agents: = 2 wks or 5 half-lives, which ever is longer) - Antibody-based anticancer ther: = 4 wks with the exception of receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitors - Chloroq/hydchloroq: > 14 ds 11 Have available a FFPE tum 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 Min life expect of 12 wks at screening 13 Ctrceptive use by men or wom should be consistent with local regulations regarding the meth of ctrception for those partic in clin studies; (estrogens are not permitted) 14 Negative pregnancy test (urine and/or serum) for wom of childbearing potential 15 Fem partics must be post-menopausal for at least 1 year, surgically sterile, or using one highly effective form of birth control Fem partics must refrain from egg cell donation and breastfeeding while on st and for at least 7 months after the last dose of st interv Non-steril male partners of a woman of childbearing potential must use a male condom plus spermicide throughout this period 16 Male partics who intend to be sexually active with a fem partner of childbearing potential must be surgically sterile or using an acceptable method of ctrception (see Appendix G) from the time of screening throughout the total duration of the st and the drug washout period (at least 4 months after the last dose of st intervention) to prevent pregnancy in a partner Male partics must not donate or bank sperm during this same time period No
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 st 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 st intervention and of low potential risk for recurrence 3 Persistent toxicities caused by previous antican ther (excluding alopecia), not yet resolved to CTCAE Version 50 Grade = 1 or baseline 4 Uncontr infection requiring IV antib, antiv, or antifun; suspected infects (eg, prodromal symptoms); or inability to rule out infections 5 Known active or uncontr 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 Uncontr 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), uncontr or signif cardiac arrhyt, or uncontr hypert (resting systolic blood pressure > 180 mmHg or diastolic blood pressure > 110 mmHg) 8 Inves judg of 1 or more of the following: - Mean resting corrected QTcF interval > 470 ms - History of QT prolong associated with other medic that requ discont of that medication, or any current concom medic 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, connec tissue or inflamm disorders with pulm involv, or prior pneum 11 Leptomeningeal carcinon 12 Clinic signif corn dis 13 Known active tuberc infect 14 Any of the foll prior antic ther: - Any treatment (including ADC) containing a chemoth agent targeting topois I - - TROP2-targeted therapy - Prior treatment with same ICC agent 15 Any conc antican treatment, with the exception of bisphosph, denos, for the treatm of bone metast 16 Concurrent use of horm therapy for non-cancer-related conds 17 Major surgical procedure (excluding placement of vasular access) or significant traumatic injury within 3 weeks of the first dose of st interv or an anticipated need for major surgery during the st 18 Receipt of live, attenuated vaccine within 30 days prior to the first dose of st treatment 19 Concom use of chr syst (IV or oral) corticoste or other immunosupp medis except for managing ade evs (inhaled sts or intra articular steroid injections are permitted in this st) 20 Previous treatment in the present st 21 Partic in another clinical st with a st interv or investig medicinal device administered in the last 4 weeks prior to first dosing, random into a prior T-DXd (trastuzumab deruxtecan) st regar of treat assig, or conc enrolment in another clinical st, unless it is an obser (noninterventional) clinical st or during the follow-up period of an interventional st 22 Participants with a known hypersensto Dato-DX
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 |
|---|---|
| Timepoint(s) of evaluation of this end point: 1. Randomization to event (response, progression, last evaluable assessment) up to 21m 2. Randomization to event up to 21m; from date of 1st response until progression or death up to 20m 3. Randomization to progression (inv. assessment) or death (up to 21m) 4. At least 11wks after randomization up to 18m 5. Randomization to start of 1st subsequent anti-cancer therapy post discontinuation of randomized treatment (up to 21m) 6. Randomization to start of 2nd subsequent anti-cancer therapy post discontinuation of 1st subsequent therapy (up to 21m) 7. Randomization to 2nd progression or death (up to 21m) 8. Randomization to 18wks post-progression 9. D1 of C1, C2, C4, C6, C8, C12 then every 4 cycles until EOT 10.D1 of C1, C2, C4, C6, C8, C12 and every 4 cycles until EOT & 28 days after last dose | — |
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 ContactInformation Center
AstraZeneca
Outcome results
None listed