SYD985 in Patients With HER2-expressing Recurrent, Advanced or Metastatic Endometrial Carcinoma

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of SYD985 in recurrent, advanced or metastatic endometrial cancer.

Detailed Description
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This is an open-label, single-arm study in patients with HER2-expressing recurrent, advanced or metastatic endometrial carcinoma. HER2-expression is defined as a 1+, 2+ or 3+ score on immunohistochemistry (IHC) or positive by in situ hybridization (ISH). Eligible patients for this study should have progressed on or after first line platinum-based chemotherapy. Patients who have had two or more lines of chemotherapy for advanced/metastatic disease are not eligible. Eligible patients will receive SYD985 until disease progression or unacceptable toxicity. Patients who have stopped study treatment for other reasons than disease progression will continue their tumor evaluations in an observation period until disease progression or start of a new anticancer therapy.

Official Title
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A Single-arm Phase II Trial to Evaluate the Safety and Efficacy of the Antibody-Drug Conjugate (ADC) SYD985 in Patients With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Endometrial Carcinoma Who Previously Progressed on or After First Line Platinum-based Chemotherapy

Conditions
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Endometrial Cancer

Intervention / Treatment
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* Drug: SYD985


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Females with histologically confirmed recurrent, advanced or metastatic endometrial carcinoma Eligible patients should have progressed on or after first line platinum-based chemotherapy for advanced/metastatic endometrial cancer. Patients who have had two or more lines of chemotherapy for advanced/metastatic disease are not eligible, taking into account the following: Patients may have received up to one additional line of chemotherapy if given in the neoadjuvant or adjuvant setting. If such treatment was completed less than 6 months prior to the current tumor recurrence or progression it is to be considered first-line treatment; No more than one line of non-cytotoxic systemic cancer therapy (such as immunotherapy, trastuzumab or protein kinase inhibitors) is allowed. HER2 tumor expression defined as a 1+, 2+ or 3+ score on IHC or positive by ISH At least one measurable cancer lesion as defined by the Response Evaluation Criteria for Solid Tumours (RECIST version 1.1); Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2; Exclusion Criteria: Current or previous use of a prohibited medication as listed in the protocol; History of infusion-related reactions and/or hypersensitivity to trastuzumab; History of keratitis; Severe, uncontrolled systemic disease at screening; Left Ventricular Ejection Fraction (LVEF) < 50%, or a history of clinically significant decrease in LVEF during previous treatment with trastuzumab; History of clinically significant cardiovascular disease; Symptomatic brain metastases, brain metastases requiring steroids to manage symptoms, or treatment for brain metastases within 8 weeks prior to randomization; 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 computed tomography (CT) scan.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SYD985<br>SYD985, Intravenous, every 3 weeks (Q3W) | Drug: SYD985<br>* SYD985 powder for concentrate for solution for infusion<br>* Other names: (vic-)trastuzumab duocarmazine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | Objective response rate is defined as the proportion of patients with an assessed best overall response of complete response or partial response according to Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | Progression-free survival is defined as the time from the date of randomization to the date of first documented disease progression by investigator assessment according to RECIST v1.1 or death due to any cause, whichever occurred earlier. | 2 years | 
| Overall Survival (OS) | Overall survival is defined as the time from date of randomization to death due to any cause. | 2-year overall survival | 
| Incidence of Treatment-Emergent Adverse Events (AEs) | AEs will be graded by the investigator as assessed by CTCAE v5.0 | 2 years |