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 progression-free survival of LY3484356 (Arm A) to the standard comparator of Investigator’s Choice Endocrine Therapy of either fulvestrant or exemestane (Arm B) |
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E.2.2 | Secondary objectives of the trial |
•To compare OS of Arm A to Arm B
•To compare other efficacy objectives of Arm A to Arm B
•To assess the safety and tolerability of each treatment arm
•To evaluate the effectiveness of Arm A compared to Arm B based on PROs of pain using the Worst Pain NRS
•To assess the PK of LY3484356 |
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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.
∙ 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 |
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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. PFS by Estrogen Receptor 1 Gene (ESR1) Mutation Status in Plasma
Investigator-assessed PFS by ESR1 mutation status in plasma
7. Progression Free Survival (PFS) by blinded independent review
8. 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."
9. Pharmacokinetics (PK): Steady State Plasma Concentrations of LY3484356
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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. Randomization to the date of first documented progression of disease or death from any cause (estimated as up to 3 years)
8. Screening through follow-up (estimated as up to 3 years)
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 | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 61 |
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 |
India |
Japan |
Korea, Republic of |
Mexico |
Russian Federation |
Taiwan |
Turkey |
Ukraine |
United States |
Austria |
Belgium |
France |
Germany |
Greece |
Italy |
Netherlands |
Spain |
Czechia |
Argentina |
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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 | 1 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial months | 7 |