Trial Title:
HS-20089 in Patients With Ovarian Cancer and Endometrial Cancer
NCT ID:
NCT06014190
Condition:
Ovarian Cancer
Fallopian Tube Cancer
Primary Peritoneal Cancer
Endometrial Cancer
Conditions: Official terms:
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Endometrial Neoplasms
Fallopian Tube Neoplasms
Conditions: Keywords:
HS-20089
B7-H4
Antibody-drug Conjugate
Ovarian Cancer
Endometrial Cancer
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
HS-20089
Description:
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.
Arm group label:
Cohort 1 at 4.8 mg/kg of HS-20089 (Phase 2a)
Arm group label:
Cohort 1 at 5.8 mg/kg of HS-20089 (Phase 2a)
Arm group label:
Cohort 2 at 5.8 mg/kg of HS-20089 (Phase 2a)
Arm group label:
Cohort 3 at 5.8 mg/kg of HS-20089 (Phase 2a)
Arm group label:
Cohort 4 at 5.8 mg/kg of HS-20089 (Phase 2a)
Arm group label:
Recommended dose of HS-20089 (Phase 2b)
Summary:
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:
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.
Criteria for 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Anhui Provincial Cancer Hospital
Address:
City:
Hefei
Country:
China
Status:
Recruiting
Facility:
Name:
Lingying Wu
Address:
City:
Beijing
Zip:
100020
Country:
China
Status:
Recruiting
Contact:
Last name:
Lingying Wu, MD
Phone:
010-87788996
Email:
wulingying@csco.org.cn
Contact backup:
Last name:
Dawei Wu
Phone:
010-87788495
Email:
cancergcp@163.com
Facility:
Name:
Peking University Cancer Hospital
Address:
City:
Beijing
Country:
China
Status:
Recruiting
Facility:
Name:
Chongqing University cancer Hospital
Address:
City:
Chongqing
Country:
China
Status:
Suspended
Facility:
Name:
Fujian Cancer Hospital
Address:
City:
Fuzhou
Country:
China
Status:
Recruiting
Facility:
Name:
Sun Yat-Sen Memorial Hospital Sun Yat-Sen University
Address:
City:
Guangzhou
Country:
China
Status:
Recruiting
Facility:
Name:
Guangxi Cancer Hospital
Address:
City:
Nanning
Country:
China
Status:
Recruiting
Facility:
Name:
Hainan General Hospital
Address:
City:
Haikou
Country:
China
Status:
Recruiting
Facility:
Name:
The fourth Hospital of Heibei Medical University
Address:
City:
Shijiazhuang
Country:
China
Status:
Recruiting
Facility:
Name:
Harbin Medical University Cancer Hospital
Address:
City:
Harbin
Country:
China
Status:
Recruiting
Facility:
Name:
Henan Cancer Hospital
Address:
City:
Zhengzhou
Country:
China
Status:
Recruiting
Facility:
Name:
Hubei Cancer University
Address:
City:
Wuhan
Country:
China
Status:
Recruiting
Facility:
Name:
Union Hospital Tongji Medical College Huazhong University of Science and Technology
Address:
City:
Wuhan
Country:
China
Status:
Recruiting
Facility:
Name:
Hunan Cancer Hosipital
Address:
City:
Changsha
Country:
China
Status:
Recruiting
Facility:
Name:
Xiangya Hospital of Central South University
Address:
City:
Changsha
Country:
China
Status:
Recruiting
Facility:
Name:
Nanjing Drum Tower Hospital
Address:
City:
Nanjing
Country:
China
Status:
Recruiting
Facility:
Name:
Jilin Cancer Hospital
Address:
City:
Changchun
Country:
China
Status:
Recruiting
Facility:
Name:
The Second Hospital of Dalian Medical University
Address:
City:
Dalian
Country:
China
Status:
Suspended
Facility:
Name:
Liaoning Cancer Hospital
Address:
City:
Shenyang
Country:
China
Status:
Recruiting
Facility:
Name:
Shengjing Hospital of China Medical University
Address:
City:
Shenyang
Country:
China
Status:
Recruiting
Facility:
Name:
Cancer Hospital of Shandong First Medical University
Address:
City:
Jinan
Country:
China
Status:
Recruiting
Facility:
Name:
Obstetrics & Gynecology Hospital of Fudan University
Address:
City:
Shanghai
Country:
China
Status:
Recruiting
Facility:
Name:
Shanxi Cancer Hospital
Address:
City:
Taiyuan
Country:
China
Status:
Recruiting
Facility:
Name:
The first Affiliated Hospital of Xi'an Jiaotong University
Address:
City:
Xi'an
Country:
China
Status:
Recruiting
Facility:
Name:
Tianjin Medical University cancer institute & Hospital
Address:
City:
Tianjin
Country:
China
Status:
Recruiting
Facility:
Name:
Affiliated Cancer Hospital of Xinjiang Medical University
Address:
City:
Xinjiang
Country:
China
Status:
Recruiting
Facility:
Name:
Yunnan Cancer Hospital
Address:
City:
Kunming
Country:
China
Status:
Recruiting
Facility:
Name:
Zhejiang Cancer Hospital
Address:
City:
Hanzhou
Country:
China
Status:
Recruiting
Start date:
December 18, 2023
Completion date:
December 31, 2027
Lead sponsor:
Agency:
Hansoh BioMedical R&D Company
Agency class:
Industry
Source:
Hansoh BioMedical R&D Company
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06014190
