E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Recurrent, Advanced or Metastatic Endometrial Carcinoma |
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E.1.1.1 | Medical condition in easily understood language |
Patients with HER2-expressing recurrent, advanced or metastatic endometrial carcinoma who previously progressed on or after first line platinum-based chemotherapy |
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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 | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10014743 |
E.1.2 | Term | Endometrial carcinoma |
E.1.2 | System Organ Class | 100000004864 |
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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 evaluate the objective tumour response rate (ORR) of SYD985. |
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E.2.2 | Secondary objectives of the trial |
To evaluate for SYD985: • Progression-free survival (PFS); • Overall survival (OS); • Safety. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Female patients, age ≥18 years at the time of signing main informed consent; 2. Patients with histologically confirmed recurrent, advanced or metastatic endometrial carcinoma (including endometrioid, mucinous, serous, squamous, clear-cell, undifferentiated or mixed carcinoma or carcinosarcoma); 3. Eligible patients should have progressed on or after one prior systemic platinum-based chemotherapy regimen for endometrial cancer. Patients who have had two or more lines of chemotherapy are not eligible: - Patients may have received up to one additional line of chemotherapy if given in the neoadjuvant or adjuvant setting provided that such treatment was completed more than 6 months prior to the current tumour recurrence or progression; - No more than one line of non-cytotoxic systemic cancer therapy (such as immunotherapy, trastuzumab or protein kinase inhibitors) is allowed. Note: there is no restriction regarding to the lines of prior hormonal therapy. 4. HER2 tumour expression defined as a 1+, 2+ or 3+ score on IHC or positive by ISH as determined by the central laboratory on most recent available/obtained tumour material; 5. At least one measurable cancer lesion as defined by the Response Evaluation Criteria for Solid Tumours (RECIST version 1.1); 6. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2; 7. Adequate organ function, evidenced by the following (local) laboratory results: – Absolute neutrophil count ≥ 1.5 x 109/L; – Platelet count ≥ 100 x 109/L; – Hemoglobin ≥ 9.0 g/dL or 5.6 mmol/L; – Total bilirubin ≤ 1.5 x the upper limit of normal (ULN); – Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x ULN (or ≤ 5.0 x ULN in the presence of liver metastases); – Serum creatinine ≤ 1.5 x ULN; 8. For women of childbearing potential highly effective contraception must be used during the study and up to at least 6 months after last study treatment. This is not required in case the patient or sole partner is surgically sterilized or in case the patient truly abstains from sexual activity. |
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E.4 | Principal exclusion criteria |
1. Having been treated with: a. Any HER2-targeting antibody-drug conjugate (ADC) therapy; b. Anthracycline treatment within 8 weeks prior to start IMP treatment; c. Other anticancer therapy including chemotherapy, immunotherapy, or investigational agents within 4 weeks prior to start IMP treatment or 5 times the half-life of the therapy, whichever is shorter; d. Radiotherapy within 4 weeks prior to start IMP treatment, or within 1 week prior to start IMP treatment for palliative care (as long as the lungs were not exposed); e. Hormone therapy within 1 week prior to start IMP treatment; The patient must have sufficiently recovered from any treatment-related toxicities to CTCAE Grade ≤ 1 (except for toxicities not considered a safety risk for the patient at the investigator’s discretion); 2. History of infusion-related reactions and/or hypersensitivity to trastuzumab or excipients of the study drug which led to permanent discontinuation of the treatment; 3. History or presence of keratitis; 4. Severe, uncontrolled systemic disease (e.g. clinically significant cardiovascular, pulmonary, or metabolic disease) at screening; 5. Left ventricular ejection fraction (LVEF) < 50% as assessed by either echocardiography or multigated acquisition (MUGA) scan at screening, or a history of clinically significant decrease in LVEF during previous treatment with trastuzumab leading to permanent discontinuation of treatment; 6. History (within 6 months prior to start IMP treatment) or presence of clinically significant cardiovascular disease such as unstable angina, congestive heart failure (CHF), myocardial infarction, uncontrolled hypertension, or cardiac arrhythmia requiring medication; 7. Symptomatic brain metastases, brain metastases requiring steroids to manage symptoms, or treatment for brain metastases within 8 weeks prior to start IMP treatment; 8. History or presence of idiopathic pulmonary fibrosis, organizing pneumonia (e.g. bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan; 9. Known active Hepatitis B, C or E infection; 10. Major surgery within 4 weeks prior to start IMP treatment; 11. Pregnancy or lactation; 12. Other condition, which in the opinion of the investigator, would compromise the safety of the patient or the patient's ability to complete the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is ORR based on investigator assessed tumour assessment according to RECIST 1.1. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Tumour assessments should include an evaluation of all known and/or suspected sites of disease, whenever possible. Patients should have lesions selected that can be evaluated at every tumour assessment. Patients with non-measurable disease whose non-target lesions are not assessed at a follow-up visit will be considered unevaluable at that visit unless PD is assessed. Tumour evaluation: Screening, Every 6 weeks for first 24 wks, thereafter every 12 wks, Treatment discontinuation Visit, Observation Phase Visits |
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E.5.2 | Secondary end point(s) |
The secondary efficacy endpoints are: • PFS; • OS; • Safety. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Survival information gathered during: Observation phase and Survival Follow up. The Observation Phase is for any patient that discontinued study treatment for reasons other than PD (e.g. toxicity). Patients stay in the Observation Phase until the time of PD or the start of a new anticancer treatment. Every 3 months (±14 days) following the last visit/contact (i.e. 30-day follow up visit or final observation phase visit) patient should be contacted for survival until death, lost to follow-up or consent withdrawal, whichever comes first. During this follow-up only survival information and initiation of new anticancer medication should be documented. Ongoing safety evaluation till Follow-up Visit. |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
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) | 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 | 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 | 1 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | No |
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 |
Korea, Democratic People's Republic of |
Poland |
Russian Federation |
Serbia |
Singapore |
Ukraine |
United States |
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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 overall study ends when the last patient completed the last study visit, discontinued from the study or is lost to follow-up. |
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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 | 3 |
E.8.9.1 | In the Member State concerned days | 11 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial days | 22 |