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. |
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E.1.1.1 | Medical condition in easily understood language |
Patients with Selected HER2 Expressing Tumors. |
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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. |
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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 (DoR, DCP, PFS, OS) - 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 |
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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. |
• Miejscowo zaawansowany, nieoperacyjny lub przerzutowy nowotwór na podstawie najnowszych wyników badań obrazowych. • Poszczególne kohorty, do których włączani są pacjenci, to: o Kohorta 1: rak dróg żółciowych o Kohorta 2: rak pęcherza moczowego o Kohorta 3 :rak szyjki macicy o Kohorta 4 :rak trzonu macicy o Kohorta 5: rak jajnika o Kohorta 6 :rak trzustki o Kohorta 7: nowotwory rzadkie: ta kohorta będzie obejmowała pacjentów z rozpoznaniem nowotworów wykazujących ekspresję HER2, z wyłączeniem nowotworów wskazanych powyżej, a także raka piersi, niedrobnokomórkowego raka płuca, raka żołądka i raka jelita grubego. • Pacjenci u których wystąpiła progresja choroby po wcześniejszym leczeniu, lub dla których nie istnieje zadowalająca alternatywna opcja leczenia. • Dozwolone jest wcześniejsze leczenie celowane nakierowane na HER2. • U pacjentów musi występować nadekspresja HER2 na podstawie oceny przeprowadzonej w laboratorium lokalnym lub centralnym. • Występowanie zmian mierzalnych, ocenianych przez badacza na podstawie kryteriów RECIST v1.1. • Wydolna czynność narządów w tym funkcji sercowo-naczyniowych, nerkowych i wątrobowych. |
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E.4 | Principal exclusion criteria |
• History of non-infectious pneumonitis/ILD that required steroids, 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 gastroesophageal junction, or non-small cell lung cancer • Medical conditions that may interfere with the subject's participation in the study. |
• Występująca w wywiadzie (niezakaźna) choroba śródmiąższowa płuc (ILD)/niezakaźne zapalenie płuc, wymagające podania sterydów, występująca obecnie ILD/niezakaźne zapalenie płuc lub sytuacja, w której nie można wykluczyć podejrzenia ILD/niezakaźnego zapalenia płuc w badaniu obrazowym podczas oceny przesiewowej • Współistniejące, klinicznie istotne ciężkie choroby dotyczące płuc • Niekontrolowane zakażenie wymagające dożylnego (i.v.) podania antybiotyków, leków przeciwwirusowych lub leków przeciwgrzybiczych • Wysięk opłucnowy, wodobrzusze lub wysięk osierdziowy, które wymagają drenażu, zastawki otrzewnowej lub leczenia wodobrzusza polegającego na reinfuzji płynu puchlinowego po usunięciu składników komórkowych (CART) • Rozpoznana somatyczna mutacja DNA w obrębie HER2 (ERBB2) bez ekspresji HER2 w komórkach guza • Pierwotne rozpoznanie gruczolakoraka piersi, gruczolakoraka okrężnicy lub odbytnicy, gruczolakoraka trzonu żołądka lub połączenia żołądkowo-przełykowego, lub niedrobnokomórkowego raka płuca • Stany chorobowe mogące zakłócać udział pacjenta w badaniu.
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E.5 End points |
E.5.1 | Primary end point(s) |
Objective Response Rate (ORR) according to RECIST v1.1, as assessed by investigator |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Approximately 30 months after the last patient is enrolled or when all patients have discontinued treatment, if earlier. |
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E.5.2 | Secondary end point(s) |
Based on RECIST 1.1, as assessed by Investigator: 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. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) 30 months after the last patient is enrolled or when all patients have discontinued treatment 2) 30 months after the last patient is enrolled or when all patients have discontinued treatment 3) 30 months after the last patient is enrolled or when all patients have discontinued treatment 4) Up to 12 months. 5) 30 months after the last patient is enrolled or when all patients have discontinued treatment 6) Up to 12 months. 7) 30 months after the last patient is enrolled or when all patients have discontinued treatment 8) 30 months after the last patient is enrolled or when all patients have discontinued treatment 9) 30 months after the last patient is enrolled or when all patients have discontinued treatment |
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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 | No |
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 | No |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 46 |
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 |
Taiwan |
Australia |
Brazil |
Canada |
India |
Korea, Republic of |
Russian Federation |
Thailand |
United Kingdom |
United States |
Belgium |
Czechia |
Italy |
Netherlands |
Poland |
Spain |
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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. |
Koniec badania („zakończenie badania”) definiuje się jako datę ostatniej wizyty/oceny określonej w protokole (w tym kontaktu telefonicznego) dla ostatniego uczestnika badania. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |