E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
High-Risk, Node-Positive, HR+, HER2+ Breast Cancer |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10029104 |
E.1.2 | Term | Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10006199 |
E.1.2 | Term | Breast cancer stage I |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare the efficacy of abemaciclib plus physician’s choice ET versus placebo plus physician’s choice ET in the study population. |
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E.2.2 | Secondary objectives of the trial |
To compare the efficacy of abemaciclib plus ET versus placebo plus physician’s choice ET in the study population. (*)To assess the safety profile of abemaciclib plus physician’s choice ET versus placebo plus ET in the study population. (*)To evaluate participant-reported symptoms, function and global health status/QOL (EORTC QLQ-C30) To evaluate health status in the study population to inform decision modeling for health economic evaluation using the EQ-5D 5L. To evaluate the PK of abemaciclib
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• The participant has confirmed HR+, HER2-positive (HER2+) in initial diagnostic tissue, early invasive breast cancer without evidence of disease recurrence or distant metastases • The participant must have undergone definitive surgery of the primary breast tumor(s) AND must be randomized within 18 months of primary breast cancer surgery. • Have tumor tissue from breast (preferred) or lymph node • Have received a minimum of four cycles of chemotherapy in either the neoadjuvant or adjuvant setting per standard of care therapy • Participants have completed approximately 9 months to one year of standard HER2-targeted therapy without evidence of disease recurrence (neoadjuvant/adjuvant combined duration). • Eligible adjuvant regimens are as follows: o Single agent adjuvant TDM-1 or o Adjuvant pertuzumab in combination with trastuzuma • Participant must have high risk disease is defined by 1 of the following: o For participants who were treated with neoadjuvant chemotherapy administered with HER2 targeted therapy: The presence axillary nodal disease detected pathologically in the surgical specimen; the presence of residual disease in the breast surgical specimen may also be detected pathologically but is not required. o For participants who were not treated with neoadjuvant therapy: Participant’s cancer must be axillary node positive (microscopic and macroscopic tumor involvement are allowed; ipsilateral internal mammary and supraclavicular lymph nodes are allowed, but will not count toward the number of positive lymph nodes) and fulfill one of the following criteria: Pathological tumor involvement in ≥4 ipsilateral axillary lymph nodes OR o Pathological tumor involvement in 1 to 3 ipsilateral axillary lymph node(s) and at least 1 of the following criteria: o Histological Grade 3 as defined by a combined score per the modified Bloom Richardson grading system (Elston and Ellis 1991), also known as the Nottingham scale, or equivalent following discussion with the Lilly CRP/CRS o Primary invasive tumor size ≥5 cm determined pathologically. |
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E.4 | Principal exclusion criteria |
• Participant has breast cancer with any of the following features: o Disease recurrence or distant metastatic disease (including contralateral axillary lymph nodes) o Lymph node-negative status o Pathological complete response (pCR) from any prior systemic treatments for early breast cancer o Inflammatory breast cancer • Participants with a history of previous breast cancer, with the exception of ipsilateral DCIS treated by locoregional therapy alone ≥5 years ago. Participants with a history of contralateral DCIS treated by local regional therapy at any time may be eligible. • The participant has previously received treatment with: o Any CDK4 and CDK6 inhibitor o Adjuvant treatment with immunotherapy, tucatinib, neratinib, investigational HER2 directed therapy, or DS8201 for treatment of breast cancer. o ET (i.e., tamoxifen, raloxifene or AI) for breast cancer prevention (without diagnosis of breast cancer). o Additional chemotherapy, anti-cancer ET, or HER2-targeted therapy beyond standard of care therapy for their breast cancer at study enrollment o Bone-targeting agents prescribed as cancer modifying treatment agent |
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E.5 End points |
E.5.1 | Primary end point(s) |
To compare invasive disease free survival (IDFS) for abemaciclib plus physician’s choice ET versus placebo plus physician’s choice ET in the study population. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After approximately 50 months from first participant randomized when approximately 324 IDFS events have occurred. |
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E.5.2 | Secondary end point(s) |
• Efficacy endpoints: overall survival (OS), distant relapse-free survival (DRFS) • Safety endpoints, including but not limited to TEAEs, SAEs, hospitalizations, clinical laboratory tests, vital signs, and physical examinations • To evaluate participant-reported symptoms, function and global health status/QOL based on EORTC QLQ-C30 scales • To evaluate health status in the study population to inform decision modeling for health economic evaluation using the EQ-5D 5L index score • To evaluate the PK of abemaciclib based on abemaciclib concentrations
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After approximately 50 months from first participant randomized when approximately 324 IDFS events have occurred. At the end of trial.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 203 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Brazil |
China |
Israel |
Japan |
Korea, Republic of |
Mexico |
Russian Federation |
Taiwan |
United States |
Austria |
Belgium |
Finland |
France |
Germany |
Hungary |
Italy |
Romania |
Spain |
Switzerland |
United Kingdom |
Argentina |
Greece |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 10 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 10 |