E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Breast Neoplasms, Neoplasm Metastasis |
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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.1.3 | 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 PFS of Imlunestrant (Arm A) to the standard comparator of Investigator's Choice Endocrine Therapy of either fulvestrant or exemestane (Arm B) in the ITT population •To compare the PFS of Arm A to Arm B in the ESR1-mutation detected population •To compare the progression-free survival of Imlunestrant plus abemaciclib (Arm C) to imlunestrant (Arm A) in the ITT population |
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E.2.2 | Secondary objectives of the trial |
•To compare OS of Arm A to Arm B in the ITT population •To compare OS of Arm A to Arm B in the ESR1-mutation detected population •To compare OS of Arm C to Arm A in the ITT population •To assess the safety and tolerability of each treatment arm •To evaluate the effectiveness of Arm A compared to Arm B and Arm C compared to Arm A based on PROs of pain using the Worst Pain NRS •To assess the PK of Imlunestrant (Arm A and Arm C) •To assess the PK of Abemaciclib and its metabolites (Arm C) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
∙ Have a diagnosis of ER+, HER2- locally advanced or metastatic breast cancer ∙ Have disease that has demonstrated progression on or after an aromatase inhibitor alone or in combination with a CDK4/6 inhibitor. oPatients are expected to have received prior treatment with a CDK4/6 inhibitor if this treatment is approved and can be reimbursed ∙ Must be deemed appropriate for treatment with endocrine therapy ∙ If female, have a postmenopausal status by natural or surgical means or by ovarian function suppression ∙ Have RECIST evaluable disease (measurable disease and/or nonmeasurable bone-only disease) ∙ Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group scale (Oken et al. 1982) ∙ Have adequate renal, hematologic, and hepatic organ function ∙ Must be able to swallow capsules/tablets |
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E.4 | Principal exclusion criteria |
∙ Have received prior treatment with chemotherapy (except for neoadjuvant/ adjuvant chemotherapy), fulvestrant, or any investigational-ER-directed therapy (including SERDs and non-SERDs), any PI3K-, mTOR- or AKT- inhibitor ∙ Have visceral crisis, lymphangitic spread within the lung, or any evidence of leptomeningeal disease. ∙ Have symptomatic or untreated brain metastasis. ∙ Have serious preexisting medical conditions that, in the judgment of the investigator, would preclude participation in this study ∙ Known allergic reaction against any of the components of the study treatment
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E.5 End points |
E.5.1 | Primary end point(s) |
1.Progression Free Survival (PFS) by investigator assessment • Investigator-assessed PFS (between Arm A and Arm B) in the ITT population • Investigator-assessed PFS (between Arm A and Arm B) in the ESR1-mutation detected population • Investigator-assessed PFS (between Arm C and Arm A) in the ITT population |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Randomization to the date of first documented progression of disease or death from any cause (estimated as up to 3 years) |
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E.5.2 | Secondary end point(s) |
2. Overall Survival (OS) 3. Objective Response Rate (ORR): Percentage of Participants Who Achieve a Confirmed Best Overall Response of Complete Response (CR) or Partial Response (PR) 4. Duration of Response (DoR) 5. Clinical Benefit Rate (CBR): Percentage of Participants Who Achieve a Best Overall Response of CR, PR or Stable Disease for greater than or equal to (≥) 24 weeks 6. Progression Free Survival (PFS) by blinded independent review 7. Patient Reported Outcomes (PRO): Time to Worsening of "Worst Pain" Measured by the Worst Pain Numeric Rating Scale (NRS). NRS is a single item, participant-administered, 11-point horizontal scale anchored at 0 and 10, with 0 representing "no pain" and 10 representing "pain as bad as you can imagine." 8. Pharmacokinetics (PK): Steady State Plasma Concentrations of Imlunestrant 9.Pharmacokinetics (PK): Steady State Plasma Concentrations of Imlunestrant and Abemaciclib
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
2. Randomization until death from any cause (estimated as up to 5 years) 3. Randomization until measured progressive disease (estimated as up to 1 year) 4. Date of CR or PR to date of disease progression or death due to any cause (estimated up to 3 years) 5. Randomization until measured progressive disease (estimated as up to 1 year) 6. Randomization to the date of first documented progression of disease or death from any cause (estimated as up to 3 years) 7. Screening through follow-up (estimated as up to 3 years) 8. Cycle 2 to Cycle 4 (cycle = 28 days) 9. Cycle 2 to Cycle 4 (cycle = 28 days)
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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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Investigator’s Choice of Endocrine Therapy |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 63 |
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 |
Argentina |
Ukraine |
Taiwan |
Australia |
Brazil |
China |
India |
Japan |
Korea, Republic of |
Mexico |
Russian Federation |
Turkey |
United States |
Austria |
Belgium |
Czechia |
France |
Germany |
Greece |
Italy |
Netherlands |
Spain |
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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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LVLS in the study or last scheduled procedure for the last participant in the trial globally |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 7 |