HS-20089 in Patients With Ovarian Cancer and Endometrial Cancer

NCT ID: NCT06014190

Last Updated: 2024-08-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

460 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-12-18

Study Completion Date

2027-12-31

Brief Summary

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HS-20089 is an investigational antibody-drug conjugate (ADC) composed of a humanized IgG1 anti-B7-H4 monoclonal antibody conjugated to the topoisomerase I inhibitor payload via a protease-cleavable linker, with an average drug-to-antibody ratio of about 6.

This is a phase 2, open-label, multi-center study to evaluate the efficacy, safety, pharmacokinetics (PK) and immunogenicity of HS-20089 as monotherapy in patients with recurrent or metastatic ovarian cancer and endometrial cancer.

Detailed Description

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This is a phase 2, open-label, multi-center study composed of two parts: phase 2a and phase 2b.

Phase 2a: This part of study will be conducted in the following four cohorts: Cohort 1: Patients with platinum-resistant ovarian cancer, fallopian tube cancer or primary peritoneal cancer. Cohort 2: Patients with recurrent or metastatic endometrial cancer who have progressed on or are intolerant to at least one line of standard platinum-based chemotherapy. Cohort 3: Patients with platinum-sensitive ovarian cancer, fallopian tube cancer or primary peritoneal cancer who have progressed on or are intolerant to at least two lines of standard platinum-based chemotherapy. Cohort 4: Patients with other advanced solid tumors who have progressed on or are intolerant to established standard therapies. Patients in cohort 1 will be randomly assigned 1:1 to receive HS-20089 at 4.8 mg/kg or 5.8 mg/kg and patients in the other three cohorts will receive HS-20089 at 5.8 mg/kg.

Phase 2b: This part of study will be conducted in the following two cohorts: Cohort 1: Patients with platinum-resistant ovarian cancer, fallopian tube cancer or primary peritoneal cancer. Cohort 2: Patients with recurrent or metastatic endometrial cancer who have progressed on or are intolerant to at least one line of standard platinum-based chemotherapy. The cohorts may be adjusted based on the observed clinical results, translational medicine data and research progress in the field. All patients will receive HS-20089 at the recommended dose (RD) determined by accumulated research data.

Conditions

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Ovarian Cancer Fallopian Tube Cancer Primary Peritoneal Cancer Endometrial Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cohort 1 at 4.8 mg/kg of HS-20089 (Phase 2a)

Patients in cohort 1 of phase 2a will be randomly assigned to receive HS-20089 at 4.8 mg/kg or 5.8 mg/kg.

Group Type EXPERIMENTAL

HS-20089

Intervention Type DRUG

All patients will receive intravenous HS-20089 once every three weeks (Q3W) until experiencing objective disease progression (except for study drug treatment beyond progression) or meeting other protocol-specified criteria of study treatment discontinuation.

Cohort 1 at 5.8 mg/kg of HS-20089 (Phase 2a)

Patients in cohort 1 of phase 2a will be randomly assigned to receive HS-20089 at 4.8 mg/kg or 5.8 mg/kg.

Group Type EXPERIMENTAL

HS-20089

Intervention Type DRUG

All patients will receive intravenous HS-20089 once every three weeks (Q3W) until experiencing objective disease progression (except for study drug treatment beyond progression) or meeting other protocol-specified criteria of study treatment discontinuation.

Cohort 2 at 5.8 mg/kg of HS-20089 (Phase 2a)

Patients in cohort 2 of phase 2a will receive HS-20089 at 5.8 mg/kg.

Group Type EXPERIMENTAL

HS-20089

Intervention Type DRUG

All patients will receive intravenous HS-20089 once every three weeks (Q3W) until experiencing objective disease progression (except for study drug treatment beyond progression) or meeting other protocol-specified criteria of study treatment discontinuation.

Cohort 3 at 5.8 mg/kg of HS-20089 (Phase 2a)

Patients in cohort 3 of phase 2a will receive HS-20089 at 5.8 mg/kg.

Group Type EXPERIMENTAL

HS-20089

Intervention Type DRUG

All patients will receive intravenous HS-20089 once every three weeks (Q3W) until experiencing objective disease progression (except for study drug treatment beyond progression) or meeting other protocol-specified criteria of study treatment discontinuation.

Cohort 4 at 5.8 mg/kg of HS-20089 (Phase 2a)

Patients in cohort 4 of phase 2a will receive HS-20089 at 5.8 mg/kg.

Group Type EXPERIMENTAL

HS-20089

Intervention Type DRUG

All patients will receive intravenous HS-20089 once every three weeks (Q3W) until experiencing objective disease progression (except for study drug treatment beyond progression) or meeting other protocol-specified criteria of study treatment discontinuation.

Recommended dose of HS-20089 (Phase 2b)

Patients of phase 2b will receive HS-20089 at recommended dose.

Group Type EXPERIMENTAL

HS-20089

Intervention Type DRUG

All patients will receive intravenous HS-20089 once every three weeks (Q3W) until experiencing objective disease progression (except for study drug treatment beyond progression) or meeting other protocol-specified criteria of study treatment discontinuation.

Interventions

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HS-20089

All patients will receive intravenous HS-20089 once every three weeks (Q3W) until experiencing objective disease progression (except for study drug treatment beyond progression) or meeting other protocol-specified criteria of study treatment discontinuation.

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hansoh BioMedical R&D Company

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Lingying Wu, MD

Role: PRINCIPAL_INVESTIGATOR

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Locations

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Anhui Provincial Cancer Hospital

Hefei, Anfei, China

Site Status RECRUITING

Lingying Wu

Beijing, Beijing Municipality, China

Site Status RECRUITING

Peking University Cancer Hospital

Beijing, Beijing Municipality, China

Site Status RECRUITING

Chongqing University cancer Hospital

Chongqing, Chongqing Municipality, China

Site Status SUSPENDED

Fujian Cancer Hospital

Fuzhou, Fujian, China

Site Status RECRUITING

Sun Yat-Sen Memorial Hospital Sun Yat-Sen University

Guangzhou, Guangdong, China

Site Status RECRUITING

Guangxi Cancer Hospital

Nanning, Guangxi, China

Site Status RECRUITING

Hainan General Hospital

Haikou, Hainan, China

Site Status RECRUITING

The fourth Hospital of Heibei Medical University

Shijiazhuang, Hebei, China

Site Status RECRUITING

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, China

Site Status RECRUITING

Henan Cancer Hospital

Zhengzhou, Henan, China

Site Status RECRUITING

Hubei Cancer University

Wuhan, Hubei, China

Site Status RECRUITING

Union Hospital Tongji Medical College Huazhong University of Science and Technology

Wuhan, Hubei, China

Site Status RECRUITING

Hunan Cancer Hosipital

Changsha, Hunan, China

Site Status RECRUITING

Xiangya Hospital of Central South University

Changsha, Hunan, China

Site Status RECRUITING

Nanjing Drum Tower Hospital

Nanjing, Jiangsu, China

Site Status RECRUITING

Jilin Cancer Hospital

Changchun, Jilin, China

Site Status RECRUITING

The Second Hospital of Dalian Medical University

Dalian, Liaoning, China

Site Status SUSPENDED

Liaoning Cancer Hospital

Shenyang, Liaoning, China

Site Status RECRUITING

Shengjing Hospital of China Medical University

Shenyang, Liaoning, China

Site Status RECRUITING

Cancer Hospital of Shandong First Medical University

Jinan, Shandong, China

Site Status RECRUITING

Obstetrics & Gynecology Hospital of Fudan University

Shanghai, Shanghai Municipality, China

Site Status RECRUITING

Shanxi Cancer Hospital

Taiyuan, Shanxi, China

Site Status RECRUITING

The first Affiliated Hospital of Xi'an Jiaotong University

Xi’an, Shanxi, China

Site Status RECRUITING

Tianjin Medical University cancer institute & Hospital

Tianjin, Tianjin Municipality, China

Site Status RECRUITING

Affiliated Cancer Hospital of Xinjiang Medical University

Xinjiang, Xinjiang, China

Site Status RECRUITING

Yunnan Cancer Hospital

Kunming, Yunnan, China

Site Status RECRUITING

Zhejiang Cancer Hospital

Hanzhou, Zhejiang, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Lingying Wu, MD

Role: CONTACT

010-87788996

Dawei Wu

Role: CONTACT

010-87788495

Facility Contacts

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Lingying Wu, MD

Role: primary

010-87788996

Dawei Wu

Role: backup

010-87788495

Other Identifiers

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HS-20089-201

Identifier Type: -

Identifier Source: org_study_id

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