HS-20089 treatment for ovarian and endometrial cancer

A Phase 2 Study of HS-20089 for Injection in Patients With Recurrent or Metastatic Ovarian Cancer and Endometrial Cancer

This study is testing a new treatment called HS-20089 to see if it can help people with recurrent or advanced ovarian and endometrial cancer feel better.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 460 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Hansoh BioMedical R&D Company (industry)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 28 sites (Hefei, Anfei and 27 other locations)
• Trial ID: NCT06014190 on ClinicalTrials.gov

What this trial studies

This phase 2, open-label, multi-center study evaluates the efficacy, safety, pharmacokinetics, and immunogenicity of HS-20089, an investigational antibody-drug conjugate, in patients with recurrent or metastatic ovarian and endometrial cancer. The study consists of two parts: phase 2a, which includes four cohorts based on the type of cancer and previous treatments, and phase 2b, focusing on patients with platinum-resistant ovarian cancer and recurrent endometrial cancer. Patients will receive HS-20089 at varying dosages depending on their cohort, with the aim of assessing its therapeutic potential as a monotherapy.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with recurrent or metastatic ovarian or endometrial cancer who have progressed on standard therapies.

Not a fit: Patients with only brain and/or bone lesions as target lesions will not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with difficult-to-treat ovarian and endometrial cancers.

How similar studies have performed: Other studies involving antibody-drug conjugates have shown promise, indicating potential for success with this approach.

Eligibility criteria

Inclusion Criteria:

1. Males or females aged 18 years or older (≥18 years).
2. Patients diagnosed with recurrent or metastatic ovarian cancer, endometrial cancer or other solid tumors.
3. Subjects have at least one target lesion as assessed per the RECIST 1.1. Patients with only brain and/or bone lesions as target lesions are ineligible.
4. Tumor tissue from a newly obtained biopsy (FFPE tumor tissue blocks or slides are acceptable) is required. If the newly obtained biopsy is not feasible, newly obtained FFPE slides cut from archival tumor tissue blocks within 2 years prior to the first dose of study drug are acceptable.
5. Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 to 1 and no deterioration within 2 weeks before the first dose.
6. Have a life expectancy of at least 12 weeks.
7. Female subjects of childbearing potential are willing to take appropriate contraceptive measures and should not breastfeed from signing the informed consent until 6 months after the last dose; male subjects must agree to use barrier contraception (i.e. condoms) from signing the informed consent to 6 months after the last dose.
8. Female subjects must have a negative pregnancy test within 7 days prior to the first dose (for subjects with tumor related abnormal elevation of human chorionic gonadotropin \[HCG\], an ultrasound of uterus and appendages should be performed within 7 days prior to the first dose to rule out pregnancy), or demonstrate no risk for pregnancy.
9. Subject must be voluntarily enrolled in this clinical trial, be able to understand the study procedures and to sign written informed consent.

Exclusion Criteria:

1. Have received or is currently receiving the following treatment:

   1. B7-H4-targeted therapies.
   2. Have received any of cytotoxic chemotherapy drugs, investigational drugs, anti-tumor traditional Chinese medicines or other anti-tumor drugs (including endocrine therapy, molecular targeted therapy, biotherapy, etc.) within 14 days prior to the first dose of study drug; or need to continue these drugs during the study.
   3. Have received macromolecular antitumor drugs (including immunotherapy, such as monoclonal antibodies and bispecific antibodies) within 28 days prior to the first dose of study drug.
   4. Have received locoregional radiation therapy within 2 weeks prior to the first dose of study drug; more than 30% of bone marrow irradiation or wide-field radiation therapy within 4 weeks prior to the first dose of study treatment.
   5. Major surgery (such as craniotomy, thoracotomy or laparotomy, etc.) within 4 weeks prior to the first dose of study treatment.
   6. Use of strong inhibitors or inducers of CYP3A4, CYP2D6, P-gp, or BCRP, or sensitive substrates of CYP3A4, CYP2D6, P-gp, or BCRP with narrow therapeutic window within 7 days prior to the first dose of study drug; or in need of continuing treatment with these drugs during the study.
   7. Current use of drugs known to prolong the QT interval or potentially cause torsades de pointes; or need to continue these medications during the study.
2. Presence of Grade ≥ 2 toxicities as per Common Terminology Criteria for Adverse Events (CTCAE version 5.0) due to prior anti-tumor therapy (except alopecia and residual neurotoxicity).
3. Presence of pleural/abdominal effusion requiring clinical intervention.
4. Known history of prior malignancy.
5. Evidence of brain metastasis, unless meeting all of the following criteria:

   1. Asymptomatic; medically stable for at least four weeks prior to the first dose;
   2. No steroid treatment required for at least two weeks prior to the first dose;
   3. No stereotactic radiation therapy, whole brain radiotherapy, and/or neurosurgical resection within 4 weeks prior to the first dose;
   4. No history of intracranial or spinal hemorrhage;
   5. Have at least one target lesion other than CNS lesion according to RECIST v1.1;
6. Inadequate bone marrow reserve or hepatic/renal functions.
7. Cardiological examination abnormality.
8. Severe, uncontrolled or active cardiovascular disorders.
9. Serious or poorly controlled diabetes.
10. Serious or poorly controlled hypertension.
11. Clinically significant bleeding symptoms or significant bleeding tendency within 1 month prior to the first dose of study treatment.
12. Serious arteriovenous thromboembolic events within 3 months prior to the first dose of study treatment.
13. Serious infections within 4 weeks prior to the first dose.
14. Have received systemic glucocorticoid therapy for more than 30 days within 30 days prior to the first dose study treatment, or require chronic (≥ 30 days) use of systemic glucocorticoids during the study, or have other acquired, congenital immunodeficiency disorders, or a history of organ transplantation.
15. Presence of active infectious diseases such as hepatitis B, hepatitis C, tuberculosis, syphilis, or human immunodeficiency virus infection, etc.
16. Current hepatic encephalopathy, hepatorenal syndrome, or Child-Pugh Class B or more severe cirrhosis.
17. Any moderate or severe lung diseases that may interfere with the detection and treatment of drug-related pulmonary toxicity or may seriously affect respiratory function.
18. History of severe neurological or psychiatric disorder.
19. Pregnant or breast-feeding women or women who intend to become pregnant during the study.
20. Attenuated live vaccination within 4 weeks prior to the first dose.
21. Allergies or hypersensitivity reactions within 4 weeks prior to the first dose. History of severe allergies (e.g., anaphylactic shock), or severe infusion-related reactions. Allergy or hypersensitivity to any component of HS-20089.
22. Subjects unlikely to comply with study procedures, restrictions and requirement as determined by the investigator.
23. Subjects with any condition that jeopardizes the safety of the patient or interferes with the assessment of the study, as judged by the investigator.

Where this trial is running

Hefei, Anfei and 27 other locations

• Anhui Provincial Cancer Hospital — Hefei, Anfei, China (RECRUITING)
• Lingying Wu — Beijing, Beijing Municipality, China (RECRUITING)
• Peking University Cancer Hospital — Beijing, Beijing Municipality, China (RECRUITING)
• Chongqing University cancer Hospital — Chongqing, Chongqing Municipality, China (SUSPENDED)
• Fujian Cancer Hospital — Fuzhou, Fujian, China (RECRUITING)
• Sun Yat-Sen Memorial Hospital Sun Yat-Sen University — Guangzhou, Guangdong, China (RECRUITING)
• Guangxi Cancer Hospital — Nanning, Guangxi, China (RECRUITING)
• Hainan General Hospital — Haikou, Hainan, China (RECRUITING)
• The fourth Hospital of Heibei Medical University — Shijiazhuang, Hebei, China (RECRUITING)
• Harbin Medical University Cancer Hospital — Harbin, Heilongjiang, China (RECRUITING)
• Henan Cancer Hospital — Zhengzhou, Henan, China (RECRUITING)
• Hubei Cancer University — Wuhan, Hubei, China (RECRUITING)
• Union Hospital Tongji Medical College Huazhong University of Science and Technology — Wuhan, Hubei, China (RECRUITING)
• Hunan Cancer Hosipital — Changsha, Hunan, China (RECRUITING)
• Xiangya Hospital of Central South University — Changsha, Hunan, China (RECRUITING)
• Nanjing Drum Tower Hospital — Nanjing, Jiangsu, China (RECRUITING)
• Jilin Cancer Hospital — Changchun, Jilin, China (RECRUITING)
• The Second Hospital of Dalian Medical University — Dalian, Liaoning, China (SUSPENDED)
• Liaoning Cancer Hospital — Shenyang, Liaoning, China (RECRUITING)
• Shengjing Hospital of China Medical University — Shenyang, Liaoning, China (RECRUITING)
• Cancer Hospital of Shandong First Medical University — Jinan, Shandong, China (RECRUITING)
• Obstetrics & Gynecology Hospital of Fudan University — Shanghai, Shanghai Municipality, China (RECRUITING)
• Shanxi Cancer Hospital — Taiyuan, Shanxi, China (RECRUITING)
• The first Affiliated Hospital of Xi'an Jiaotong University — Xi’an, Shanxi, China (RECRUITING)
• Tianjin Medical University cancer institute & Hospital — Tianjin, Tianjin Municipality, China (RECRUITING)
• Affiliated Cancer Hospital of Xinjiang Medical University — Xinjiang, Xinjiang, China (RECRUITING)
• Yunnan Cancer Hospital — Kunming, Yunnan, China (RECRUITING)
• Zhejiang Cancer Hospital — Hanzhou, Zhejiang, China (RECRUITING)

Study contacts

• Principal investigator: Lingying Wu, MD — Cancer Institute and Hospital, Chinese Academy of Medical Sciences
• Study coordinator: Lingying Wu, MD

Conditions: Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Cancer, Endometrial Cancer, HS-20089, B7-H4, Antibody-drug Conjugate