A Study of Dato-DXd Versus Investigator's Choice Chemotherapy in Inoperable or Metastatic Hormone Receptor-positive, HER2-negative Breast Cancer

Phase 1

• Conditions: Inoperable or Metastatic Hormone Receptor-Positive, HER2-Negative Breast Cancer that Have Been Treated With One or Two Prior Lines of Systemic Chemotherapy; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2020-005620-12-IT
• Lead Sponsor: ASTRAZENECA AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-10-18
• Last Update Posted: 2 March 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 700

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

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified