SHR - A1811 Versus Chemotherapy for Platinum-resistant Recurrent Epithelial Ovarian Cancer

NCT06990503 | Not Yet Recruiting Phase 3

• 1 other identifier: 2025-TJ-OVA1811R
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a randomized, open-label, active-controlled, multicenter phase III clinical trial. It is planned to enroll 300 subjects with platinum-resistant recurrent epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer with HER2 expression. The randomization will be stratified according to the following factors: 1) HER2 immunohistochemistry (IHC) expression status (HER2 IHC 1+ versus HER2 IHC 2+/3+); 2) whether the subject has previously received vascular endothelial growth factor/vascular endothelial growth factor receptor (VEGF/VEGFR) inhibitors such as bevacizumab (yes versus no). Subjects will be randomly assigned in a 1:1 ratio to receive either the experimental treatment group (SHR - A1811) or the control treatment group (chemotherapy chosen by the investigator, namely liposomal doxorubicin, paclitaxel, topotecan, or gemcitabine).

Conditions

Ovarian Cancer

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  Progression - Free Survival (PFS) as assessed by the Independent Radiological Review Committee (IRC) based on the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). It is defined as the time from the randomization date of the subject to the first date of documented radiological tumor progression or the date of death due to any cause, whichever occurs first.

  5 Years after treatment.

Secondary Outcomes (6)

• Overall Survival (OS)

  5 Years after treatment.

• Objective Response Rate (ORR):

  5 Years after treatment.

• Duration of Response (DoR)

  5 Years after treatment.

• Disease Control Rate (DCR)

  5 Years after treatment.

• Response Rate (RR)

  5 Years after treatment.

Study Arms (2)

SHR-A1811 Administration

EXPERIMENTAL

SHR-A1811 will be administered intravenously (IV) on Day 1 (D1) of each treatment cycle at a dose of 4.8 mg/kg. Treatment will be repeated every 3 weeks (one treatment cycle) , and will continue until the occurrence of any event meeting the protocol-defined criteria for treatment discontinuation.

Drug: SHR-A1811

Chemotherapy Administration

ACTIVE COMPARATOR

The investigator shall select one of the following treatment regimens (determined prior to randomization), and the treatment will be continued until the occurrence of any event meeting the protocol - defined criteria for treatment discontinuation. 1. Liposomal doxorubicin Liposomal doxorubicin will be administered intravenously on Day 1 of each cycle at a dose of 40 mg/m², with one treatment cycle lasting 4 weeks. 2. Paclitaxel Paclitaxel will be given intravenously on Days 1, 8, 15, and 22 of each cycle at a dose of 80 mg/m² per administration, and one treatment cycle is 4 weeks. 3. Topotecan Topotecan will be administered intravenously on Days 1, 8, and 15 of each cycle at a daily dose of 4 mg/m², with a treatment - cycle duration of 4 weeks. 4. Gemcitabine Gemcitabine will be infused intravenously on Days 1 and 8 of each cycle at a daily dose of 1000 mg/m², and each treatment cycle is 3 weeks.

Drug: Chemotherapy

Interventions

SHR-A1811 DRUG

Injection SHR - A1811 (hereinafter referred to as SHR - A1811) is an antibody - drug conjugate (ADC) targeting the HER2 protein, independently developed by Suzhou Shengdeya Biopharmaceutical Co., Ltd. (hereinafter referred to as the "sponsor"). It is composed of a recombinant humanized anti - HER2 IgG1 monoclonal antibody (SHR - 1805) conjugated with a small molecule component, SHR169106.

SHR-A1811 Administration

Chemotherapy DRUG

The treatment regimens for the control group are as follows: Liposomal doxorubicin: Administered intravenously on Day 1 of each 4 - week treatment cycle at a dose of 40 mg/m². Paclitaxel: Given intravenously on Days 1, 8, 15, and 22 of each 4 - week treatment cycle at a dose of 80 mg/m² per administration. Topotecan: Intravenously infused on Days 1, 8, and 15 of each 4 - week treatment cycle at a daily dose of 4 mg/m². Gemcitabine: Infused intravenously on Days 1 and 8 of each 3 - week treatment cycle at a daily dose of 1000 mg/m².

Chemotherapy Administration

Eligibility Criteria

• Age: 18 Years - 80 Years
• Gender Eligibility Details: ovarian cancer patients
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient voluntarily participates in this trial and signs the informed consent form.
• Female, aged 18 - 75 years old (including the boundary values, calculated from the date of signing the informed consent form).
• Pathologically confirmed epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer by tissue or cytology.
• Previously treated with a platinum - containing regimen and confirmed as platinum - resistant recurrence (platinum - resistant recurrence is defined as disease progression \[PD\] during platinum - containing therapy or within \<183 days after the last dose of platinum - containing drugs). If the patient has only received 1 line of platinum - containing treatment, at least 4 cycles of platinum - containing drugs must be received. The determination of platinum - resistant recurrence must have clear documented radiological progression. After platinum resistance, at most 1 line of systemic anti - tumor treatment has been received, and the patient is suitable for single - agent chemotherapy in the next line of treatment.
• Patients with known high expression of folate receptor α (FRα) must have received treatment with mirvetuximab soravtansine, unless the investigator judges that the patient is intolerant or unsuitable for mirvetuximab soravtansine treatment, or the treatment is not approved or unavailable locally, in which case they can be enrolled.
• Disease progression during or after the last - line treatment, or toxicity that is intolerable (with clear evidence).
• HER2 expression confirmed by the central laboratory: IHC 1+, 2+, or 3+; the patient needs to provide sufficient fresh or archived tumor tissue specimens for the sponsor - designated central laboratory to test the HER2 expression level (paraffin blocks, paraffin - embedded sections, or fresh tissue sections are all acceptable, and the scoring criteria for HER2 testing are determined by the central laboratory).
• At least one measurable lesion that meets the RECIST v1.1 criteria (according to the RECIST v1.1 requirements, the long diameter of the measurable lesion on spiral computed tomography \[CT\] scan is ≥10 mm or the short diameter of the enlarged lymph node is ≥15 mm); lesions that have been locally treated can be selected as target lesions if there is clear evidence that they have significantly progressed compared with the post - treatment state.
• ECOG PS score: 0 - 1 points.
• Expected survival time ≥12 weeks.
• Laboratory tests within 7 days before randomization confirm that the functions of important organs meet the following requirements (no blood components or cytokines can be used within 14 days before the tests):
• Absolute neutrophil count ≥1.5×10⁹/L;
• Platelet count ≥100×10⁹/L;
• Hemoglobin ≥90 g/L;
• Serum total bilirubin (TBIL) ≤1.5×the upper limit of normal (ULN);

You may not qualify if:

• Pathologically confirmed sarcoma histological subtypes, including hybrid tumors containing sarcomatous components.
• Subjects with untreated or active central nervous system (CNS) tumor metastases. Subjects with a history of leptomeningeal metastasis or current leptomeningeal metastasis. Subjects whose CNS tumor metastases have undergone adequate local treatment (surgery or radiotherapy), do not require hormone therapy, have neurologically returned to baseline (except for residual signs or symptoms related to CNS treatment), and have been stable for ≥4 weeks can be enrolled.
• Subjects who have previously received topoisomerase I inhibitors (including but not limited to irinotecan and topotecan), or ADC drugs containing topoisomerase I inhibitors, such as Enhertu (DS - 8201a), U3 - 1402, etc.
• Subjects who have received systemic anti - tumor treatment within 4 weeks before the start of the study treatment. If the previous anti - tumor treatment was small - molecule targeted therapy, the interval between the end of treatment and the first study treatment should be no less than 5 half - lives of the drug or 7 days.
• Subjects with symptomatic, poorly controlled, or moderate - to - severe pleural effusion, pericardial effusion, or ascites; subjects who have undergone effusion drainage (except diagnostic thoracentesis) can be enrolled if they have been stable for at least 2 weeks after drainage (local treatment within the serous cavity according to routine diagnosis and treatment is allowed before signing the informed consent form).
• Subjects who have completed palliative radiotherapy within 7 days before the first dose.
• Subjects with a history of other malignancies in the past or currently having other malignancies, except for cured basal cell carcinoma of the skin, cervical intraepithelial neoplasia, ductal carcinoma in situ of the breast, papillary thyroid carcinoma, and other malignancies that have been adequately treated and cured for ≥3 years before randomization with evidence proving no recurrence or metastasis.
• Subjects with a history of interstitial pneumonia/interstitial lung disease or non - infectious pneumonia (such as radiation pneumonitis) that required steroid treatment; subjects with current or suspected interstitial pneumonia/interstitial lung disease, non - infectious pneumonia, or other active pneumonias; and subjects who experienced ≥Grade 3 interstitial pneumonia during previous treatment with immune checkpoint inhibitors.
• Subjects with active pulmonary tuberculosis; subjects who have undergone adequate treatment before randomization and have stopped anti - tuberculosis treatment for ≥3 months can be enrolled.
• Subjects with known pulmonary damage caused by concurrent pulmonary diseases, including but not limited to any potential pulmonary diseases (for example, pulmonary embolism, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, etc. within 3 months before the first dose).
• Subjects with autoimmune, connective tissue, or inflammatory diseases involving the lungs (such as rheumatoid arthritis, Sjögren's syndrome, sarcoidosis, etc.), or subjects who have previously undergone lobectomy or pneumonectomy.
• Subjects with uncontrolled cardiac clinical symptoms or diseases, such as: (1) Heart failure of Grade 2 or above defined by the New York Heart Association (NYHA) criteria or left ventricular ejection fraction (LVEF) \<50%; (2) Unstable angina; (3) Myocardial infarction within 1 year before randomization; (4) Clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention; (5) Fridericia - corrected QT interval (QTcF) \>470 ms; (6) Hypertension that cannot be well controlled by drugs (subjects whose blood pressure is controlled at ≤160/100 mmHg with drugs can be enrolled).
• Subjects who have experienced arterial or venous thrombotic events within 1 month before randomization, including but not limited to cerebrovascular accidents and deep vein thrombosis; subjects with intramuscular vein thrombosis or catheter - related thrombosis of the infusion port before randomization can be included if the investigator judges there is no risk.
• Subjects who have experienced gastrointestinal perforation or fistula, urethral fistula, or abdominal abscess within 3 months before randomization; subjects who have undergone artificial fistulization or ureteral stent placement and are considered stable by the investigator after evaluation can be enrolled.
• Subjects with intestinal obstruction or symptoms and signs of intestinal obstruction or those requiring parenteral nutrition within 3 months before the start of the study treatment. However, subjects who have undergone surgical treatment and the obstruction has been completely relieved can be screened; subjects who have previously undergone intestinal stent implantation and the stent has not been removed until the screening period.

Sponsors & Collaborators

• Tongji Hospital: lead

Study Sites (1)

Tongji Hospital

Wuhan, Hubei, 430030, China

Location

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

Drug Therapy

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Qinglei Gao

  Tongji Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Qinglei Gao

CONTACT

+86-27-83662681; qingleigao@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: May 18, 2025
• First Posted: May 25, 2025
• Study Start: June 1, 2025
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): June 1, 2035
• Last Updated: May 25, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)