E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of unresectable and/or metastatic solid tumors harboring specific HER2 activating mutations regardless of tumor histology. |
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E.1.1.1 | Medical condition in easily understood language |
Patients with advanced solid tumors carrying specific HER2 mutations. |
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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 | 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 harboring specific HER2 activating mutations across 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 harboring pre-specified HER2 activating mutations across tumor types. - To assess the safety and tolerability of T-DXd. - To assess the PK of T-DXd, total anti-HER2 antibody and MAAA-1181a 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 |
• Adults ≥18 years old. Other age restrictions may apply as per local regulations. • Unresectable and/or metastatic solid tumors with pre-specified HER2 mutations locally determined by NGS, who have progressed following prior treatment or who have no satisfactory alternative treatment options. • Prior HER2 targeted therapy is permitted. • All patients must provide an FFPE tumor sample for retrospective central HER2 testing. • LVEF ≥50% • ECOG 0-1 |
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E.4 | Principal exclusion criteria |
• HER2 overexpressing (IHC3+ or IHC2+/ISH+) breast, gastric or gastroesophageal junction adenocarcinoma. • HER2 mutant NSCLC. • History of non-infectious pneumonitis/ILD, current ILD, or where suspected ILD cannot be ruled out by imaging at screening • Lung-specific intercurrent clinically significant severe illnesses. • History of active primary immunodeficiency, known HIV, active HBV or HCV infection • 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). • Has spinal cord compression or clinically active central nervous system metastases. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Confirmed objective response rate by RECIST v1.1 based on independent central review (ICR). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
An average of approximately 12 months. |
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E.5.2 | Secondary end point(s) |
1) Duration of response (DoR) based on ICR assessment. 2) Disease control rate (DCR) based on ICR assessment. 3) Progression free survival (PFS) based on ICR assessment. 4) Confirmed Objective Response Rate (ORR) based on investigator assessment. 5) Overall survival (OS). 6) Occurrence of adverse events (AEs) and serious adverse events (SAEs). 7) Pharmacokinetics (PK) assessed by serum concentration of T-DXd, total anti-HER2 antibody and MAAA-1181. 8) 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) An average of approximately 12 months. 2) An average of approximately 12 months. 3) An average of approximately 12 months. 4) An average of approximately 12 months. 5) An average of approximately 20 months. 6) An average of approximately 14 months. 7) An average of approximately 14 months. 8) An average of approximately 14 months. |
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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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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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.8.3 |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 |
Japan |
Korea, Republic of |
United States |
Belgium |
France |
Italy |
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 is defined as the time of the final DCO (data cutoff) for the final analysis. Final analysis is planned to be performed when the last patient has had the opportunity for approximately 32 weeks of follow-up after treatment assignment. |
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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 | |
E.8.9.1 | In the Member State concerned months | |
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 | 2 |