Clinical trial NCT06925113: A Retrospective, Non-interventional, Multicenter Study to Investigate the Prevalence of HER2 IHC 3+ and Characterize the Clinicopathologic Features of Gynecologic Cancers in Taiwan
Official title: A Retrospective, Non-interventional, Multicenter Study to Investigate the Prevalence of HER2 IHC 3+ and Characterize the Clinicopathologic Features of Gynecologic Cancers in Taiwan -The HERGYN Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Cervical Cancers
Endometrial Cancer
Ovarian Cancer
Keywords: gynecology
HER2 IHC
prevalence
Taiwan
retrospective
Lead sponsor: Daiichi Sankyo Taiwan Ltd.
Sponsor class: INDUSTRY
First posted: 2025-04-13
Enrollment: 510
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Recurrent or advanced endometrial cancer, ovarian cancer, or cervical cancer

Brief summary: Trastuzumab Deruxtecan (T-DXd) is a humanized anti-HER2 monoclonal antibody covalently linked to DXd, which is a topoisomerase 1 inhibitor. T-DXd has been approved for the treatment of HER2-positive breast cancer, HER2-mutated lung cancer, HER2-positive gastric cancer, and HER2-low breast cancer in Taiwan. Aside from clinical benefits in the above cancers, the DESTINY-PanTumor02 (NCT04482309) Phase II trial showed that T-DXd continued to demonstrate clinically meaningful and durable responses and survival benefits in previously treated patients across multiple HER2-expressing advanced solid tumors.

Among multiple types of solid tumors in the DESTINY-PanTumor02 trial, T-DXd showed a high confirmed objective response rate in heavily treated HER2 IHC 3+ endometrial cancer (EC, 84.6%, 11/13), ovarian cancer (OC, 63.6%, 7/11), and cervical cancer (CC, 75%, 6/8).

Previous evidence showed that HER2-expressing gynecologic cancers have limited treatment options and have poor prognoses under standard therapies. Data from DESTINY-PanTumor02 therefore serve as supporting evidence for T-DXd to become a potential therapeutic option for these HER2-expressing gynecologic cancers.

In August 2023, T-DXd received the FDA-designated breakthrough therapy designations and was approved in April 2024 for treating unresectable and metastatic HER2 IHC 3+ solid tumors that have progressed after prior treatment or lack satisfactory alternative options. The National Comprehensive Cancer Network (NCCN) has included T-DXd as a treatment option for HER2-positive endometrial, ovarian, and cervical carcinomas in their guidelines as of V1 2024.

However, the HER2 IHC 3+ prevalence rate in recurrent advanced endometrial, ovarian, and cervical cancers in Taiwan is still unclear. Only limited information regarding HER2 amplification rate by ISH is available from specific cancer types.

In this retrospective, non-interventional study, we aim to explore the prevalence of HER2 IHC 3+ in recurrent advanced endometrial, ovarian, and cervical cancers in Taiwan. The clinicopathologic characteristics will also be described using the information abstracted from the medical charts to better understand and characterize the patient profile of recurrent advanced endometrial, ovarian, and cervical cancers in Taiwan.

Detailed description: It is a non-interventional, multicenter, retrospective study to investigate the prevalence rate of HER2 IHC 3+ determined by IHC and characterize the clinicopathologic features of recurrent advanced endometrial, ovarian, and cervical cancers in Taiwan. The study plans to include approximately 170 patients with endometrial cancer, 170 patients with ovarian cancer, and 170 patients with cervical cancer from five hospitals in Taiwan.

The study will retrospectively review the medical charts to screen potential patients for study enrollment. A pathologist investigator meeting aligned with ASCO/CAP guidelines for scoring HER2 in Gastroesophageal Adenocarcinoma \[8\] will be held to ensure the concordance of IHC scoring among different sites before patient enrollment.

Once enrolled, the study will collect the most recent and qualified archived tissue samples from recurrent advanced tumors of eligible patients to perform HER2 IHC test using Ventana 4B5 assay by pathologists per standard operational procedures at each hospital (after pathologist investigator meeting). If the patient already had HER2 IHC slides stained with Ventana 4B5 assay from recurrent advanced tumors, the pathologist will rescore the HER2 IHC data without conducting HER2 IHC staining again.

For patients who have archived primary tumor tissue samples before recurrence (2024 or before, regardless of FIGO stage), the study will also collect the primary tumor tissue samples before recurrence, which are qualified and sufficient for performing HER2 IHC test using Ventana 4B5 assay by pathologists per standard operational procedures at each hospital to analyze the changes in HER2 status after recurrence. If the patient already had HER2 IHC slides stained with Ventana 4B5 assay from the primary tumors before recurrence, the pathologist will rescore the HER2 IHC data without conducting HER2 IHC staining again.

In addition to the HER2 IHC test, patient-level data including demographics, clinicopathologic characteristics, standard and exploratory diagnostic information (e.g., histopathology and biomarkers), and the clinical presentation of gynecologic cancers (e.g., FIGO stage, metastatic sites, etc.) will be abstracted from medical charts of enrolled patients after de-identification.

Eligibility criteria: Inclusion Criteria:

1. Adults aged ≥ 18 years when their clinical data are reviewed
2. Patients who fulfill ONE of the following criteria

   * Imaging or histological diagnosis of recurrent advanced endometrial cancer during 2022 to 2024, AND have tissue samples from recurrent advanced tumor (regardless of lines of received treatment) during 2022 to 2024 for HER2 IHC test (most recent and qualified pre-enrollment tumor sample must be provided)
   * Imaging or histological diagnosis of recurrent advanced ovarian cancer during 2022 to 2024, AND have tissue samples from recurrent advanced tumor (regardless of lines of received treatment) during 2022 to 2024 for HER2 IHC test (most recent and qualified pre-enrollment tumor sample must be provided)
   * Imaging or histological diagnosis of recurrent advanced cervical cancer during 2022 to 2024, AND have tissue samples from recurrent advanced tumor (regardless of lines of received treatment) during 2022 to 2024 for HER2 IHC test (most recent and qualified pre-enrollment tumor sample must be provided)

Exclusion Criteria:

1. Without FFPE tumor sample from recurrent advanced tumors (specimens with limited tumor content and fine needle aspirates are inadequate for defining tumor HER2 status)
2. With the retrospective nature and the use of anonymous clinical data, IRB/IEC/EC may grant permission to waive informed consent in this study. If the informed consent is not waived, patients or representatives who are not willing to provide written informed consent cannot be enrolled.

Primary outcomes:
measure: To understand the prevalence rate of HER2 IHC 3+ in recurrent advanced endometrial cancer, ovarian cancer, and cervical cancer in Taiwan
timeFrame: from 2022 to 2024
Secondary outcomes:
measure: To understand the prevalence rate of HER2 IHC 2+, 1+, and 0 in recurrent advanced endometrial cancer, ovarian cancer, and cervical cancer in Taiwan
timeFrame: from 2022 to 2024
Other outcomes:
measure: To assess changes in HER2 IHC status between primary tumor before recurrence and recurrent advanced tumor
timeFrame: from 2022 to 2024
measure: To assess the correlation between HER2 IHC status and other biomarkers in gynecologic cancers
timeFrame: from 2022 to 2024
Locations:
city: Taipei
country: Taiwan
facility: Daiichi Sankyo Taiwan Ltd.
Study officials:
affiliation: Daiichi Sankyo Taiwan Ltd.
name: Annie Yang
role: STUDY_DIRECTOR
References: