Study of Dato-DXd Versus Standard Chemotherapy in patient with Inoperable or MetastaticHormone Receptor-Positive, HER2-Negative Breast Cancer who has been failed on previous chemotherapy

Phase 3

• Conditions: Health Condition 1: C509- Malignant neoplasm of breast of unspecified site

• Registration Number: CTRI/2022/03/040959
• Lead Sponsor: ASTRAZENECA AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 27 May 2024

Recruitment & Eligibility

• Status: Closed to Recruitment of Participants
• Sex: Not specified
• Target Recruitment: 0

Inclusion Criteria

I.Age must be above or equal to 18 years, male or female

II.Inoperable or metastatic HR-positive, HER2-negative breast cancer (per ASCO/CAP guidelines, on local laboratory results)

III.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.

IV.Eligible for one of the chemotherapy options listed as ICC (eribulin, capecitabine, vinorelbine, gemcitabine), per investigator assessment.

V.ECOG PS of 0 or 1.

VI.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.

VII.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.

VIII.Adequate organ and bone marrow function within 7 days before day of first dosing as follows: - Hemoglobin: = 9.0 g/dL, 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 Gilberts 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)

IX.LVEF = 50% by either an echocardiogram or MUGA within 28 days of first dosing.

X.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),Chloroquine/hydroxychloroquine: > 14 days.

XI.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).

XII.Minimum life expectancy of 12 weeks at screening.

XIII.Negative pregnancy test (urine and/or serum) for women of childbearing potential

XIV.Female participants must be post-menopausal for at least 1 year, surgically sterile, or using one highly effective form of birth control

XV.Male participants who

Exclusion Criteria

I.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 investigators opinion, makes it undesirable for the participant to participate in the study or that would jeopardize compliance with the protocol.

II.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.

III.Persistent toxicities caused by previous anticancer therapy (excluding alopecia), not yet resolved to CTCAE Version 5.0 Grade = 1 or baseline.

IV.Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals; suspected infections (eg, prodromal symptoms); or inability to rule out infections.

V.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.

VI.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 load, CD4+ counts/levels > 250, 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.

VII.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).

VIII.Investigator judgment of 1 or more of the following: - Mean resting corrected QTcF interval > 470 ms, obtained from triplicate ECGs performed at screening.

IX.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.

X.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, Sjogrens, sarcoidosis etc), or prior pneumonectomy.

XI.Leptomeningeal carcinomatosis.

XII.Clinically significant corneal disease.

XIII.Known active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice).

XIV.Any of the following prior anticancer therapies: - Any treatment (including ADC) containing a chemotherapeutic agent targeting topoisomerase I or Prior treatment with same ICC agent

XV.Any concurrent anticancer treatment, with the exception of bisphosphonates, denosumab, for the treatment of bone metastases.

XVI.Concurrent u

Study & Design

• Study Type: Interventional
• Study Design: Not specified