NIPH Clinical Trials Search

JAPANESE
国立保健医療科学院
JRCT ID: jRCT2031210440

Registered date:22/11/2021

A Study of Dato-DXd Versus ICC in Inoperable or Metastatic HR-positive, HER2-negative Breast Cancer

Basic Information

Recruitment status Not Recruiting
Health condition(s) or Problem(s) studiedBreast Cancer
Date of first enrollment25/01/2022
Target sample size700
Countries of recruitmentArgentina,Japan,Belgium,Japan,Brazil,Japan,Canada,Japan,China,Japan,France,Japan,Germany,Japan,Hungary,Japan,India,Japan,Italy,Japan,Korea,Japan,Mexico,Japan,Nethelands,Japan,Poland,Japan,Russia,Japan,South Africa,Japan,Spain,Japan,Taiwan,Japan,United Kingdom,Japan,United States,Japan
Study typeInterventional
Intervention(s)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 Choice of Chemotherapy (ICC) -Capecitabine Tablet. Oral route of administration. Active comparator -Gemcitabine IV Infusion. Active comparator -Eribulin IV Infusion. Active comparator Other Name: Eribulin Mesylate -Vinorelbine IV Infusion. Active comparator

Outcome(s)

Primary Outcome1. Progression Free Survival [ Time Frame: From randomization until progression as assessed by BICR or death due to any cause (anticipated to be 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. The measure of interest is the hazard ratio of PFS. 2. Overall Survival [ Time Frame: Approximately 44 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 Outcome1.Objective Response Rate (ORR) [ Time Frame: Randomization to event (response, progression, last evaluable assessment) anticipated to be up to 21 months ] 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) [ Time Frame: From randomization to event up to 21 months; from date of first response until progression or death up to 20 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/Investigator assessment or death due to any cause. 3.Progression-Free Survival by Investigator assessment [ Time Frame: From randomization to progression (investigator assessment) or death (anticipated to be up to 21 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 cause in the absence of progression), (ie, date of event or censoring - date of randomization + 1). 4.Disease Control Rate (DCR) [ Time Frame: At least 11 weeks after randomization up to 18 months. ] 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 Frame: From randomization to start of first subsequent anti-cancer therapy post discontinuation of randomized treatment (anticipated to be up to 21 months) ] 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 Frame: From randomization to start of second subsequent anti-cancer therapy post discontinuation of first subsequent therapy (anticipated to be up to 21 months) ] 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 Frame: From randomization to second progression or death (anticipated to be up to 21 months) ] 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 local standard clinical practice. 8.Clinical Outcome Assessment- TTD in pain [ Time Frame: From randomization to 18 weeks post-progression ] The secondary PRO endpoints include: TTD in pain as measured by the pain scale from EORTC QLQ-C30 9.Pharmacokinetics of Dato-DXd [ Time Frame: From first dose to end of treatment (anticipated to be up to 21 months). ] Plasma concentrations of Dato-DXd, total anti-TROP2 antibody, and MAAA-1181a (payload). 10.Immunogenicity [ Time Frame: From first dose to end of treatment safety follow-up (anticipated to be up to 22 months). ] To test for the presence of ADA to investigate the immunogenicity of Dato-DXd. 11.Clinical Outcome Assessment- TTD in physical Functioning [ Time Frame: From randomization to 18 weeks post-progression ] The secondary PRO endpoints include: TTD in physical functioning as measured by the physical functioning scale from EORTC QLQ-C30 12.Clinical Outcome Assessment- TTD in GHS [ Time Frame: From randomization to 18 weeks post-progression ] The secondary PRO endpoints include: TTD in GHS/QoL as measured by the GHS/QoL scale from EORTC QLQ-C30

Key inclusion & exclusion criteria

Age minimum>= 18age old
Age maximumNot applicable
GenderBoth
Include criteriaAge 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: <= 1.5 x ULN if no liver metastases; or <=3 x ULN in the presence of documented Gilbert's syndrome (unconjugated hyperbilirubinemia) or liver metastases at baseline. - ALT and AST: <= 3 x ULN for AST/ALT; however, if elevation is due to liver metastases, <= 5.0 x ULN is allowed. - Calculated creatinine clearance: >= 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% 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, whichever is longer). - Antibody-based anticancer therapy: >= 4 weeks with the exception of receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitors (eg, denosumab for the treatment of bone metastases). - Immunotherapy (non-antibody-based therapy): >= 2 weeks or 5 times the terminal elimination T1/2 of the agent, whichever is longer. - Chloroquine/hydroxychloroquine: > 14 days. 11. All participants must have available a FFPE tumor sample (block preferred, or a minimum of 20 freshly cut slides), at the time of screening. This can be from either the primary disease setting (surgical resection or diagnostic sample), or from a metastatic lesion (excluding bone) for tissue-based analysis (including but not restricted/limited to IHC staining of potential predictive biomarkers as well as tumor mutational analysis). The mandatory FFPE tumor sample submitted for analysis should be obtained as close to the time of diagnosis of metastatic or inoperable disease as possible. If neither an adequate FFPE block nor the minimum of 20 slides are available, a patient may still be considered eligible. In this situation, approval by the Study Team for patient's entry into the study is required. 12. Minimum life expectancy of 12 weeks at screening. Sex 13. Male or female. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies; however, oral estrogens are not permitted. Reproduction 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 (a highly effective method of contraception is defined as one that can achieve a failure rate of less than 1% per year when used consistently and correctly). For female contraception, Women of childbearing potential who are sexually active with a non sterilized male partner must agree to use one highly effective method of birth control. They should have been stable on their chosen method of birth control starting at a minimum of 3 months before C1D1 to at least 7 months after the last dose . 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 (condom alone in countries where spermicides are not approved) 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 a highly effective method of contraception from the time of screening throughout the total duration of the study and the drug washout period (at least 4 months after the last dose of study intervention) to prevent pregnancy in a partner. Male participants must not donate or bank sperm during this same time period. Not engaging in heterosexual activity (sexual abstinence) for the duration of the study and drug washout period is an acceptable practice if this is the preferred usual lifestyle of the participant; however, periodic or occasional abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. Female partners of male participants are allowed to use HRT for contraception. Informed Consent 17. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. 18. Provision of signed and dated written Optional Genetic Research Information informed consent prior to collection of sample for optional genetic research that supports Genomic Initiative.
Exclude criteria1. 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 <= 1 or baseline. Note: participants may be enrolled with some chronic, stable Grade 2 toxicities (defined as no worsening to > 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 < 2000 IU/mL ii. Have normal transaminase values, or, if liver metastases are present, abnormal transaminases, with a result of AST/ALT <3 x ULN, which are not attributable to HBV infection iii. Start or maintain antiviral treatment if clinically indicated as per the investigator 6. Known HIV infection that is not well controlled. All of the following criteria are required to define an HIV infection that is well controlled: undetectable viral RNA, CD4+ count > 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 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, obtained from triplicate ECGs performed at screening. -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. Note: Participants found to have ILD/pneumonitis on baseline screening chest CT are not eligible. 10. Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (ie, pulmonary emboli within three months of first dosing, severe asthma, severe COPD, restrictive lung disease, pleural effusion etc), or any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement (ie, Rheumatoid arthritis, Sjogren's, sarcoidosis etc), or prior pneumonectomy. 11. Leptomeningeal carcinomatosis. 12. Clinically significant corneal disease. 13. Known active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice). Prior/Concomitant Therapy 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 (Note: Participants are eligible for enrolment into this study if they able to receive treatment with another ICC agent not previously received; see Inclusion Criterion 4) 15. Any concurrent anticancer treatment, with the exception of bisphosphonates, denosumab, for the treatment of bone metastases. 16. Concurrent use of systemic hormonal replacement therapy (eg, estrogen). However, concurrent use of hormones for non-cancer related conditions (eg, insulin for diabetes) is acceptable. 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. Prior/Concurrent Clinical Study Experience 19. Previous treatment in the present study. 20. Participation in another clinical study with a study intervention or investigational medicinal device administered in the last 4 weeks prior to first dosing, randomization into a prior T-DXd (trastuzumab deruxtecan) study regardless of treatment assignment, or concurrent enrolment in another clinical study, unless it is an observational (noninterventional) clinical study or during the follow-up period of an interventional study. 21. Participants with a known hypersensitivity to Dato-DXd, or any of the excipients of the product (including, but not limited to, polysorbate 80). 22. Known history of severe hypersensitivity reactions to other monoclonal antibodies. Other Exclusions 23. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site). 24. Judgment by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions and requirements. 25. For women only, currently pregnant (confirmed with positive pregnancy test) or breastfeeding, or who are planning to become pregnant.

Related Information

Contact

Public contact
Name Contact for Clinical Trial Information
Address 1-2-58, Hiromachi, Shinagawa-ku, Tokyo Tokyo Japan 140-8710
Telephone +81-3-6225-1111
E-mail dsclinicaltrial@daiichisankyo.co.jp
Affiliation DAIICHI SANKYO Co.,Ltd.
Scientific contact
Name Akihiro Inoguchi
Address 1-2-58, Hiromachi, Shinagawa-ku, Tokyo Tokyo Japan 140-8710
Telephone +81-3-6225-1111
E-mail dsclinicaltrial@daiichisankyo.co.jp
Affiliation DAIICHI SANKYO Co.,Ltd.