E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment in locally advanced unresectable metastatic patients with HER2 overexpressed (IHC 3+ or IHC 2+) and HER2 low (1+) selected solid tumors not eligible for curative therapy. |
Trattamento di tumori solidi selezionati, localmente avanzati, non resecabili, metastatici, che esprimono HER2 (IHC 3+ or IHC 2+) and HER2 low (1+), per cui non esiste un’opzione terapeutica alternativa |
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E.1.1.1 | Medical condition in easily understood language |
Patients with Selected HER2 Expressing Tumors. |
Trattamento di tumori che esprimono HER2 |
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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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the efficacy of T-DXd in patients with metastatic or unresectable tumors in selected HER2 expressing tumor types. |
Valutare l'efficacia di T-DXd in pazienti con tumori metastatici o non resecabili che esprimono HER2 |
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E.2.2 | Secondary objectives of the trial |
- To further assess the efficacy of T-DXd in patients with metastatic or unresectable tumors in selected HER2-expressing tumor types - To assess the safety and tolerability of T-DXd - To assess the PK of T-DXd, total anti-HER2 antibody and MAAA-1181 in serum - To investigate the immunogenicity of T-DXd |
- Per valutare ulteriormente l'efficacia di T-DXd in pazienti con tumori metastatici o non resecabili in tipi di tumori selezionati che esprimono HER2 - Valutare la sicurezza e la tollerabilità di T-DXd - Per valutare la PK di T-DXd, anticorpo anti-HER2 totale e MAAA-1181 nel siero - Studiare l'immunogenicità di T-DXd |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Locally advanced, unresectable, or metastatic disease based on most recent imaging. • The respective cohorts for patient inclusion are: - Cohort 1: Biliary tract cancer - Cohort 2: Bladder cancer - Cohort 3: Cervical cancer - Cohort 4: Endometrial cancer - Cohort 5: Epithelial ovarian cancer - Cohort 6: Pancreatic cancer - Cohort 7: Rare tumors: This cohort will consist of patients with tumors that express HER2, excluding the tumors mentioned above, and breast, non-small cell lung cancer, gastric cancer, and colorectal cancer. • Progressed following prior treatment or who have no satisfactory alternative treatment option. • Prior HER2 targeting therapy is permitted. • HER2 expression for eligibility may be based on local or central assessment. • Has measurable target disease assessed by the Investigator based on RECIST version 1.1. • Has protocol- defined adequate organ function including cardiac, renal and hepatic function. |
• Malattia localmente avanzata, non resecabile o metastatica sulla base delle immagini più recenti. • Le rispettive coorti per l'inclusione dei pazienti sono: - Coorte 1: Tumori del tratto biliare - Coorte 2: Tumore della vescica - Coorte 3: Tumore della cervice - Coorte 4: Tumore dell’endometrio - Coorte 5: Tumore delle ovaie - Coorte 6: Tumore del pancreas - Coorte 7: Tumori rari : questa coorte sarà composta da pazienti con tumori che esprimono HER2, esclusi i tumori sopra menzionati, e tumore al seno, tumore del polmone non a piccole cellule, tumore gastrico e tumore del colon-retto. • Progressione dopo un trattamento precedente o mancanza di opzioni terapeutiche alternative • È consentita una precedente terapia di targeting HER2. • L' elegibilità può essere basata su una valutazione locale o centrale dell'espressione di HER2 • Presenza di malattia target valutata dallo sperimentatore sulla base della versione RECIST 1.1. • Funzione organica adeguatamente definita dal protocollo, inclusa la funzione cardiaca, renale ed epatica. |
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E.4 | Principal exclusion criteria |
• Uncontrolled intercurrent illness • History of non-infectious pneumonitis/ILD, current ILD, or where suspected ILD that cannot be ruled out by imaging at screening • Lung-specific intercurrent clinically significant severe illnesses • Uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals • Pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART • Known Somatic DNA mutation of HER2 (ERBB2) without tumoral HER2 protein expression. • Primary diagnosis of adenocarcinoma of the breast, adenocarcinoma of the colon or rectum, adenocarcinoma of the gastric body or gastro-esophageal junction, or non-small cell lung cancer. |
• Malattia intercorrente incontrollata • Storia di polmonite non infettiva / ILD, ILD in corso o sospetta ILD che non può essere esclusa dall'Imaging Screening • Malattie gravi intercorrenti clinicamente significative specifiche del polmone • Infezione non controllata che richiede antibiotici per via endovenosa (IV), antivirali o antimicotici • Versamento pleurico, ascite o versamento pericardico che richiede drenaggio, shunt peritoneale o Cell-free and Concentrated Ascites Reinfusion Therapy (CART) • Mutazione nota del DNA somatico di HER2 (ERBB2) senza espressione della proteina HER2 tumorale. • Diagnosi primaria di adenocarcinoma della mammella, del colon o del retto, del corpo gastrico o della giunzione gastro-esofagea o carcinoma polmonare non a piccole cellule. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Objective Response Rate (ORR). |
Il tasso di risposte obiettive (ORR) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
An average of approximately 12 months. |
Una media di circa 12 mesi. |
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E.5.2 | Secondary end point(s) |
1) Duration of response (DoR). 2) Disease control rate (DCR). 3) Progression free survival (PFS). 4) Proportion of patients alive and progression-free at 6 months and 12 months. 5) Overall survival (OS). 6) Proportion of patients alive at 6 months and 12 months. 7) Occurrence of adverse events (AEs) and serious adverse events (SAEs). 8) Pharmacokinetics (PK) assessed by serum concentration of T-DXd, total anti-HER2 antibody and MAAA-1181. 9) The immunogenicity of T-DXd assessed by the presence of ADAs for T-DXd. |
1) Durata della risposta (DoR). 2) Tasso di controllo della malattia (DCR). 3) Sopravvivenza libera da progressione (PFS). 4) Proporzione di pazienti vivi e liberi da progressione a 6 mesi e 12 mesi. 5) Sopravvivenza globale (OS). 6) Proporzione di pazienti vivi a 6 mesi e 12 mesi. 7) Presenza di eventi avversi (EA) ed eventi avversi gravi (SAEs). 8) Farmacocinetica (PK) valutata in base alla concentrazione sierica di T-DXd, anticorpo totale anti-HER2 e MAAA-1181. 9) L'immunogenicità di T-DXd valutata dalla presenza di ADA per T-DXd. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) An average of approximately 18 months. 2) An average of approximately 18 months. 3) An average of approximately 18 months. 4) Up to 12 months. 5) An average of approximately 30 months. 6) Up to 12 months. 7) An average of approximately 24 months. 8) An average of approximately 24 months. 9) An average of approximately 24 months. |
1) Una media di circa 18 mesi. 2) Una media di circa 18 mesi. 3) Una media di circa 18 mesi. 4) Fino a 12 mesi. 5) Una media di circa 30 mesi. 6) Fino a 12 mesi. 7) Una media di circa 24 mesi. 8) Una media di circa 24 mesi. 9) Una media di circa 24 mesi. |
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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 | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 7 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 45 |
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 | Information not present in EudraCT |
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 |
Canada |
India |
Korea, Republic of |
Russian Federation |
Taiwan |
Thailand |
United States |
Belgium |
France |
Italy |
Netherlands |
Poland |
Spain |
United Kingdom |
Czechia |
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E.8.7 | Trial has a data monitoring committee | No |
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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The end of the study (“study completion”) is defined as the date of the last protocol-specified visit/assessment (including telephone contact) for the last participant in the study. |
La fine dello studio ("conclusione dello studio") è definita come la data dell'ultima visita / valutazione stabilita dal protocollo (incluso il contatto telefonico) per l'ultimo partecipante allo studio. |
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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 | 3 |
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 | 3 |
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 |