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

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

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

Study Overview

• Status: Completed
• Conditions: Endometrial Cancer
• Intervention / Treatment: Drug: SYD985

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seongnam-si, Korea, Republic of, 13605
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of, 3080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 6351
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 6591
    • The Catholic University of Korea, Seoul St. Mary's Hospital
  • Seoul, Korea, Republic of, 3722
    • Severance Hospital, Yonsei University Health System
• Poland
  • Kraków, Poland, 30-820
    • MedTrials
  • Lublin, Poland, 20-090
    • St. John of Dukla Oncology Center of Lublin Land
• Russian Federation
  • Arkhangelsk, Russian Federation, 163045
    • Arkhangelsk Clinical Oncology Center
  • Chelyabinsk, Russian Federation, 454087
    • Chelyabinsk Regional Clinical Oncology and Nuclear Medicine Center
  • Irkutsk, Russian Federation, 664035
    • Regional Oncology Center
  • Omsk, Russian Federation, 644013
    • Clinical Oncology Center
  • Orenburg, Russian Federation, 460021
    • Orenburg Regional Clinical Oncology Center
  • Saint Petersburg, Russian Federation, 196603
    • Private Medical Institution "Evromedservis"
  • Sochi, Russian Federation, 354057
    • Oncology Center #2
  • St. Petersburg, Russian Federation, 197082
    • AV Medical Group
  • St. Petersburg, Russian Federation, 196247
    • Oncology Center of Moskovskiy District
  • Tambov, Russian Federation, 392013
    • Tambov Regional Oncological Clinical Center
  • Ufa, Russian Federation, 450054
    • Republican Clinical Oncology Center
  • Volgograd, Russian Federation, 400138
    • Volgograd Regional Clinical Oncology Center
• Serbia
  • Belgrade, Serbia, 11000
    • National Cancer Research Center
  • Nis, Serbia, 18000
    • Clinical Center Nis, Clinic of Oncology
  • Sremska Kamenica, Serbia, 21204
    • Oncology Institute of Vojvodina (IOV), Clinic of Surgical Oncology, Department of Gynecology
• Singapore
  • Singapore, Singapore, 169610
    • National Cancer Centre Singapore
  • Singapore, Singapore, 119074
    • National University Hospital, Department of Hematology-Oncology
• Ukraine
  • Cherkasy, Ukraine, 18099
    • Cherkasy Regional Oncology Dispensary of Cherkasy Oblast Council
  • Chernivtsi, Ukraine, 58013
    • Chernivtsi Regional Clinical Oncology Center
  • Dnipro, Ukraine, 49102
    • "City Clinical Hospital #4" under Dnipro City Council
  • Ivano-Frankivsk, Ukraine, 76018
    • Prykarpattia Clinical Oncology Center
  • Kharkiv, Ukraine, 61070
    • Communal Non-Profit Enterprise "Regional Center of Oncology"
  • Kharkiv, Ukraine, 61024
    • State Institution: S.P. Hryhoriev Institute of Medical Radiology under the Ukrainian Academy of Medical Sciences
  • Kyiv, Ukraine, 3039
    • Medical Center "Verum"
  • Odesa, Ukraine, 65025
    • Odesa Regional Clinical Hospital
  • Ternopil, Ukraine, 46023
    • Public Non-Profit Enterprise Ternopil Regional Clinical Oncology Center
  • Vinnytsia, Ukraine, 21029
    • Podilla Regional Oncology Center
  • Zaporizhzhia, Ukraine, 69059
    • Medical Center ONCOLIFE LLC
• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06520-8063
      • Smilow Cancer Hospital (Yale)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SYD985; SYD985, Intravenous, every 3 weeks (Q3W)	Drug: SYD985; SYD985 powder for concentrate for solution for infusion; Other Names: Trastuzumab vc-seco-DUBA; (vic-)trastuzumab duocarmazine

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Byondis B.V.
• Investigators: Study Director: Norbert Koper, Byondis B.V., The Netherlands

Study record dates

Study Major Dates

• Study Start (Actual): May 28, 2020
• Primary Completion (Actual): January 26, 2023
• Study Completion (Actual): April 25, 2023

Study Registration Dates

• First Submitted: December 12, 2019
• First Submitted That Met QC Criteria: December 17, 2019
• First Posted (Actual): December 19, 2019

Study Record Updates

• Last Update Posted (Actual): January 5, 2024
• Last Update Submitted That Met QC Criteria: January 4, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Endometrial Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Trastuzumab
• Other Study ID Numbers: SYD985.003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No