E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HER2-Low, Hormone Receptor Positive Breast Cancer which has Progressed on Endocrine Therapy in the Metastatic Setting. |
Rak piersi o niskiej ekspresji HER2 i dodatnim statusie receptora hormonalnego, z progresją po leczeniu hormonalnym choroby przerzutowej |
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E.1.1.1 | Medical condition in easily understood language |
Advanced breast cancer |
Zaawansowany rak piersi |
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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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• To assess the efficacy of Trastuzumab deruxtecan (T-DXd) compared with investigator’s choice chemotherapy in terms of PFS by BICR in the HR+, HER2-low (IHC 2+/ISH- and IHC 1+) populations. |
Ocena skuteczności trastuzumabu derukstekanu (T DXd) w porównaniu do chemioterapii zgodnej z wyborem badacza pod względem czasu przeżycia wolnego od progresji (PFS) ocenionego w sposób niezależny centralnie (BICR) w populacji o dodatnim statusie HR (HR+) i niskiej ekspresji HER2 (IHC 2+/ISH- oraz IHC 1+) |
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E.2.2 | Secondary objectives of the trial |
Key secondary objectives: • Assess the efficacy of T-DXd compared with investigator's choice chemotherapy in terms of OS in HR+, HER2-low (HER2 IHC 2+/ISH- and IHC 1+) population • Assess the efficacy of T-DXd compared with investigator's choice chemotherapy in terms of PFS by BICR and OS in ITT (HER2 IHC>0<1+ and HER2-low) population Other secondary objectives: • PFS by investigator assessment in the HR+ HER2-low population • ORR and DoR by BICR and investigator assessment in the HR+ HER2-low and ITT population • PFS2 according to investigator assessment, time to first subsequent treatment or death (TFST) and time to second subsequent treatment or death (TSST) in the HR+ HER2-low and the ITT population • Safety and tolerability of T-DXd compared to investigator's choice chemotherapy • PK of T-DXd • Symptoms, functioning and HRQoL in patients treated with T-DXd compared to investigator's choice single agent chemotherapy • Immunogenicity of T-DXd |
Kluczowe cele drugorzędowe: • ocena skuteczności T-DXd w porównaniu do chemioterapii zgodnej z wyborem badacza pod względem OS w populacji HR+, populacji HER2-low (HER2 IHC 2+/ISH- oraz IHC 1+) • ocena skuteczności T-DXd w porównaniu do chemioterapii zgodnej z wyborem badacza pod względem PFS oceniony w sposób niezależny centralnie (BICR) oraz OS w populacji ITT (populacja HER2 IHC >0 <1+ oraz populacja HER2-low ) Pozostałe cele drugorzędowe: •PFS w ocenie badacza w populacji HR+ HER2-low •ORR i DoR oceniane w sposób niezależny centralnie (BICR) i przez badacza w populacji HR+ HER2-low oraz ITT •PFS2 w ocenie badacza, TFST i TSST w populacji HR+ HER2-low i w populacji ITT •Ocena profilu bezpieczeństwa i tolerancji T-DXd w porównaniu do chemioterapii zgodnej z wyborem badacza •Ocena PK leku T DXd •Ocena HRQoL u pacjentów przyjmujących T DXd w porównaniu z chemioterapią jednoskładnikową zgodną z wyborem badacza • Ocena immunogenności T-DXd |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Key Inclusion Criteria: • Patients must be ≥18 years of age. • Pathologically documented breast cancer that: a. is advanced or metastatic b. has a history of HER2-low or negative expression by local test, defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested) or HER2 IHC 0 (ISH- or untested) c. has HER2-low or HER2 IHC >0 <1+ expression as determined by the central laboratory result established on a tissue sample taken in the metastatic disease setting d. was never previously HER2-positive e. has documented HR+ disease in the metastatic disease setting. • Has adequate tumor samples for assessment of HER2 status • Disease progression on at least 2 previous lines of endocrine therapy with or without a targeted therapy (Progression of disease within 24 months on adjuvant ET is considered a line of therapy) or disease progression on endocrine therapy + CDK4/6 inhibitor within 6 months of starting first line treatment for metastatic disease and considered appropriate for chemotherapy as the next treatment by the investigator. • No prior chemotherapy for advanced or metastatic breast cancer. • Has protocol-defined adequate organ and bone marrow function. The most recent results must be used to meet this inclusion criteria |
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E.4 | Principal exclusion criteria |
Key Exclusion Criteria: • Ineligible for all options in the investigator's choice chemotherapy arm. Patients with contraindications to capecitabine, paclitaxel, and nabpaclitaxel treatment, per local prescribing information, cannot be enrolled • Uncontrolled intercurrent illness or significant cardiovascular disease • Active or prior documented ILD/pneumonitis that required steroids or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening. • Lung-specific intercurrent clinically significant illnesses • Patients with spinal cord compression or active clinically central nervous system metastasis. •Concurrent enrolment in another clinical study, unless it is - an observational (non-interventional) clinical study - during the follow up period of a prior interventional study (prescreening for this study while a patient is on treatment in another clinical study is acceptable) •Have received a study treatment from a prior interventional study, administered in the last 30 days prior to first dose of this study treatment |
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E.5 End points |
E.5.1 | Primary end point(s) |
• PFS by BICR according to RECIST 1.1 in the HR+, HER2-low population |
• PFS oceniony w sposób niezależny centralnie (BICR), według kryteriów oceny odpowiedzi w guzach litych RECIST 1.1 w populacji HR+ z niską ekspresją HER2 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Until progression or death, assessed up to approximately 60 months. |
Do wystąpienia progresji lub zgonu, oceniane do około 60 miesięcy |
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E.5.2 | Secondary end point(s) |
The key secondary endpoints are: 1. Overall Survival (OS) - in HR+ HER2-low population 2. Progression Free Survival (PFS) - in intent to treat (ITT) population (HER2 IHC >0 <1+ and HER2-low) 3. OS - in ITT population (HER2 IHC >0 <1+ and HER2-low)
The other secondary endpoints are: 1. Objective Response Rate (ORR) and Duration of response (DoR) - in HR+, HER-2 low population 2. PFS by Investigator assessment - in the HR+, HER2-low population 3. ORR and DoR - in the ITT population 4. PFS2 by Investigator assessment, time to first subsequent therapy (TFST) and time to second subsequent treatment or death (TSST) - in HR+, HER2-low and the ITT population 5. Safety and tolerability of T-DXd compared to chemotherapy. 6. The pharmacokinetics (PK) of T-Dxd 7. Health-related quality of life 8. Immunogenicity of T-Dxd |
Kluczowymi drugorzędowymi punktami końcowymi są: 1. Ogólne przeżycie (OS) w populacji HR+ z niską ekspresją HER2 2. Czas przeżycia wolny od progresji (PFS) w populacji populacja zgodnej z zamiarem leczenia (ITT) (populacja HER2 IHC >0 <1+ oraz populacja z niską ekspresją HER2) 3. OS w populacji ITT
Pozostałe drugorzędowe punkty końcowe: 1. wskaźnik odpowiedzi obiektywnej (ORR) i czas trwania odpowiedzi (DoR) w populacji HR+ z niską ekspresją HER2 2. PFS na podstawie oceny badacza w populacji HR+ z niską ekspresją HER2 3. ORR i DoR w populacji ITT 4. Czas do drugiej progresji choroby (PFS2) na podstawie oceny badacza, czas do rozpoczęcia stosowania pierwszej kolejnej terapii lub zgonu (TFST), czas do rozpoczęcia stosowania drugiej kolejnej terapii lub zgonu (TSST w populacji HR+ z niską ekspresją HER2 i w populacji ITT 5. Ocena profilu bezpieczeństwa i tolerancji T-DXd w porównaniu do chemioterapii 6. Ocena farmakokinetyki (PK) T-DXd 7. Ocena jakości życia związanej ze zdrowiem (HRQoL) 8. Ocena immunogenności T-DXd |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The timepoints for key secondary endpoints are: Please see section secondary endpoints for corresponding timepoints below 1. Until death, assessed up to approximately 60 months 2. Until progression or death, assessed up to approximately 60 months 3. Until death, assessed up to approximately 60 months
The timepoints for other secondary endpoints are: 1. Until progression, assessed up to approximately 60 months 2. Until progression or death, assessed up to approximately 60 months 3. Until progression, assessed up to approximately 60 months 4. Assessed up to approximately 60 months 5. Up to follow-up period, approximately 60 months 6. Up to Cycle 8, approximately Week 24 7. Assessed up to approximately 60 months 8. Up to follow-up period, approximately 60 months |
Moment ewaluacji kluczowych drugorzędowych punktów końcowych 1. Do odnotowania zgonu, oceniane do około 60 miesięcy 2. Do wystąpienia progresji lub zgonu, oceniane do około 60 miesięcy 3. Do odnotowania zgonu, oceniane do około 60 miesięcy
Moment ewaluacji pozostałych drugorzędowych punktów końcowych: 1. Do wystąpienia progresji, oceniane do około 60 miesięcy 2. Do wystąpienia progresji lub zgonu, oceniane do około 60 miesięcy 3. Do wystąpienia progresji, oceniane do około 60 miesięcy 4. Oceniane do około 60 miesięcy 5. Do okresu obserwacji, około 60 miesięcy 6. Do 8 cyklu, około 24 tygodnie 7. Oceniane do około 60 miesięcy 8. Do okresu obserwacji, około 60 miesięcy |
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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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
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 | No |
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 |
Chemioterapia jednoskładnikowa zgodna z wyborem badacza: kapecytabina, paklitaksel, nab-paklitaksel |
Investigator’s choice single agent chemotherapy: capecitabine, paclitaxel, nab-paclitaxel |
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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
| 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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 105 |
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 |
Singapore |
Taiwan |
Australia |
Brazil |
Canada |
China |
India |
Israel |
Japan |
Korea, Republic of |
Mexico |
Russian Federation |
Saudi Arabia |
United Kingdom |
United States |
Austria |
Belgium |
Denmark |
France |
Germany |
Hungary |
Italy |
Netherlands |
Poland |
Portugal |
Spain |
Sweden |
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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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Completing the last expected visit/contact of the last patient undergoing the study. He/she has completed all phases of the study as per SoAs (including follow-up for OS). Patients may be withdrawn from the study if the study itself is stopped. The study may be terminated at individual centers if the study procedures are not being performed according to ICH GCP or if recruitment rate does not allow to complete study in the planned timeframe. |
Odbycie ostatniej oczekiwanej wizyty/kontaktu przez ostatniego pacjenta uczestniczącego w badaniu. Pacjent/pacjentka ukończył(a) wszystkie fazy badania zgodnie z harmonogramem badań (SoAs) (w tym okres obserwacji do oceny OS).
Badanie może zostać zakończone w poszczególnych ośrodkach, jeżeli procedury badania nie są wykonywane zgodnie z ICH GCP lub jeśli wskaźnik rekrutacji nie pozwala na ukończenie badania w planowanym terminie.
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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 | 6 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |