A Phase Ib/II Clinical Study of HRS-1167 in Combination With Bevacizumab in Patients With Recurrent Ovarian Cancer

This study is a multicenter, open-label Phase Ib/II clinical trial to observe and evaluate the safety, tolerability and pharmacokinetics of HRS-1167 in combination with bevacizumab in patients with recurrent ovarian cancer mechanical characterization and preliminary evaluation of the efficacy of HRS-1167 in combination with bevacizumab in patients with recurrent ovarian cancer.

Study Overview

• Status: Recruiting
• Conditions: Recurrent Ovarian Cancer
• Intervention / Treatment: Drug: Bevacizumab； HRS-1167

• Study Type: Interventional
• Enrollment (Estimated): 54
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Xin Xu; Phone Number: 0518-82342973; Email: xin.xu@hengrui.com
• Study Contact Backup: Name: Yuting Wang; Phone Number: 0518-82342973; Email: yuting.wang@hengrui.com

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230002
      • Not yet recruiting
      • First Affiliated Hospital of University of Science and Technology of China
      • Principal Investigator: Ying Zhou
  • Beijing
    • Beijing, Beijing, China, 100021
      • Not yet recruiting
      • Cancer Hospital Chinese Academy of Medical Sciences
      • Principal Investigator: Lingying Wu
    • Beijing, Beijing, China, 100142
      • Not yet recruiting
      • Beijing Cancer Hospital
      • Principal Investigator: Hong Zheng
  • Chongqing
    • Chongqing, Chongqing, China, 400016
      • Not yet recruiting
      • The First Affiliated Hospital of Chongqing Medical University
      • Principal Investigator: Junying Tang
    • Chongqing, Chongqing, China, 400000
      • Not yet recruiting
      • Chongqing University Cancer Hospital
      • Principal Investigator: Yu Huang
  • Guangxi
    • Nanning, Guangxi, China, 530022
      • Not yet recruiting
      • Guangxi Medical University Affiliated Tumor Hospital
      • Principal Investigator: He Wang
  • Hebei
    • Shijiazhuang, Hebei, China, 050001
      • Not yet recruiting
      • The Fourth Hospital of Hebei Medical University
      • Principal Investigator: Hui Zhang
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150001
      • Not yet recruiting
      • Harbin Medical University Cancer Hospital
      • Principal Investigator: Ge Lou
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Not yet recruiting
      • Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology
      • Principal Investigator: Qinglei Gao
  • Hunan
    • Changsha, Hunan, China, 410013
      • Recruiting
      • Hunan Cancer Hospital
      • Principal Investigator: Jing Wang
  • Liaoning
    • Shenyang, Liaoning, China, 110042
      • Not yet recruiting
      • Liaoning cancer hospital
      • Principal Investigator: Danbo Wang
  • Shandong
    • Jinan, Shandong, China, 250000
      • Not yet recruiting
      • Qilu Hospital of Shandong University
      • Principal Investigator: Hualei Bu
  • Shangdong
    • Jinan, Shangdong, China, 250117
      • Not yet recruiting
      • Shandong First Medical University Affiliated Cancer Hospital
      • Principal Investigator: Liang Chen
  • Shanxi
    • Taiyuan, Shanxi, China, 030006
      • Not yet recruiting
      • Shanxi Provincial Cancer Hospital
      • Principal Investigator: Hongwei Zhao
  • Sichuan
    • Chengdu, Sichuan, China, 610042
      • Not yet recruiting
      • Sichuan Cancer Hospital
      • Principal Investigator: Guonan Zhang
  • Tianjin
    • Tianjin, Tianjin, China, 300000
      • Not yet recruiting
      • Tianjin Cancer Hospital
      • Principal Investigator: Ke Wang
  • Yunnan
    • Kunming, Yunnan, China, 650118
      • Not yet recruiting
      • Yunnan Cancer Hospital
      • Principal Investigator: Hongying Yang
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310005
      • Not yet recruiting
      • Zhejiang Cancer Hospital
      • Principal Investigator: Tao Zhu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Voluntarily join this study, sign the informed consent form, have good compliance, and be able to cooperate with the follow-up.
2. Age 18~75 years old.
3. Cytologically or histologically confirmed diagnosis of recurrent epithelial ovarian, fallopian tube, or primary peritoneum cancer.
4. Patient has been previously treated with a platinum-containing regimen and has been treated with a platinum-based regimen during the last dose of platinum-based therapy (self-treatment initiation to within 1 month after the last dose) efficacy is non-PD, 6 months after the end of treatment (183 disease progression or recurrence within calendar days, and the number of lines of systemic therapy after platinum resistance ≤1 line.
5. At least one measurable lesion per RECIST v1.1 criteria.
6. ECOG PS score: 0-1 points.
7. Expected survival period ≥ 3 weeks.
8. Good level of organ function.
9. Subjects of childbearing potential who need to use highly effective contraception from the time of signing informed to 210 days after the last dose of trial drug; Subjects of childbearing potential must have a negative serum HCG within 7 days prior to the first dose and must be non-lactating.

Exclusion Criteria:

1. Those who have received chemotherapy, immune checkpoint inhibitors, major surgical operations, anti-tumor vaccines within 4 weeks before the first dose; Those who have received palliative radiotherapy within 2 weeks prior to the first dose; Oral molecularly targeted therapy (including other clinical trial targeted agents) 5 drug half-lives or 4 weeks (whichever is shorter) < from the first study dose; Those who have received a live vaccine within 4 weeks prior to the first dose or possibly during the study.
2. Toxicity due to prior antineoplastic therapy has not recovered according to NCI-CTCAE v5.0 grade≤ Level 1.
3. Subject has previous or concurrent other malignancies.
4. Subject has carcinomatous meningitis, or has untreated central nervous system metastases.
5. Imaging shows tumor invasion of large blood vessels or unclear demarcation from blood vessels; or the investigator judges that the patient's tumor has a high possibility of invading important blood vessels and causing fatal hemorrhage during treatment.
6. Cancerous ascites and pleural effusion with clinical symptoms, requiring puncture and drainage; or those who have received ascites, pleural effusion drainage within 14 days before the first dose of the drug.
7. Severe bone injury due to tumor bone metastases, including severe bone pain with poor control, pathological fractures of important sites and spinal cord that have occurred within the last 6 months or are expected to occur in the near future oppression, etc.
8. Previous or current interstitial pneumonitis/interstitial lung disease (except for those with radiographic changes only), pneumonia requiring systemic treatment with glucocorticoids (such as radiation pneumonitis, etc.); Current active pneumonitis or those with severe impairment of lung function confirmed by pulmonary function tests.
9. People who are known to be allergic to bevacizumab or have had a severe allergic reaction to other monoclonal antibodies.
10. Those with active tuberculosis; Those who have been adequately treated before the first dose and have discontinued anti-tuberculosis therapy for ≥ 3 months can be enrolled.
11. Have hypertension that is not well controlled with antihypertensive medication (systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 90 mmHg); Previous hypertensive crisis or hypertensive sex encephalopathy.
12. Have clinical symptoms or disease of the heart that are not well controlled.
13. Coagulation abnormalities, bleeding tendency, or those receiving thrombolytic or anticoagulant therapy are allowed to receive low-dose low-molecular-weight heparin or oral aspirin prophylactic anticoagulation therapy during the trial.
14. NCI-CTCAE v5.0 grade ≥2 bleeding events within 4 weeks prior to the first dose, including but not limited to hemoptysis (hemoptysis in a single episode ≥2mL), vaginal bleeding, gastrointestinal bleeding, etc.
15. Experienced arterior/venous thrombotic event within 6 months prior to the first dose.
16. Patients with gastrointestinal perforation or fistula (except artificial fistula), urethral fistula, intra-abdominal abscess, intestinal obstruction, or those requiring parenteral nutrition within 3 months prior to the first dose.
17. Those who are unable to swallow tablets normally, or have abnormal gastrointestinal function, which may affect drug absorption as judged by the investigator.
18. Subjects who have had a serious infection within 1 month before the first dose, including but not limited to infectious complications requiring hospitalization, bacteremia, severe pneumonia, etc.; Subjects with any active infection requiring intravenous system therapy, or who have a progeny during the screening period, prior to the first dose 38.5°C due to unknown fever>; Those who have used antibiotics within 2 weeks before the first dose.
19. Known history of positive human immunodeficiency virus (HIV) test; Known active hepatitis.
20. Treatment with a strong inhibitor of CYP3A4, CYP2D6, P-gp, or BCRP, <5 drug half-lives or 14 days from the date of first dose; Treatment with the above enzyme strong inducers was 28 days < the first dose.
21. As judged by the investigator, there are other factors that may affect the results of the study or cause the study to be terminated halfway, such as alcoholism, drug abuse, other serious diseases (such as severe diabetes, thyroid disease, spinal cord compression, superior vena cava syndrome, psychiatric diseases) that require concomitant treatment, serious laboratory test abnormalities, accompanied by family or social factors, which will affect the safety of the subjects.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HRS-1167 in combination with bevacizumab in patients with recurrent ovarian cancer	Drug: Bevacizumab； HRS-1167; Bevacizumab: injection, 100mg(4mL), intravenous infusion HRS-1167: Tablets, 25mg/tablet, oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The number of subjects with dose-limiting toxicity (DLT)	From first dose of study treatment until the end of Cycle 1（up to 21 days）
Determination of Recommended Phase II dose (RP2D)	From first dose of study treatment until the end of Cycle 1（up to 21 days）

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	The percentage of participants with a confirmed CR or PR according to RECIST v1.1 criteria.	From time of first dose of HRS-1167 or Bevacizumab until the date of objective disease progression or death (up to 24 months)]
Disease Control Rate (DCR)	The percentage of participants who have a best objective response of confirmed CR or PR or who have SD for at least 15 weeks after start of treatment	From time of first dose of HRS-1167 or Bevacizumab until the date of objective disease progression or death (up to 24 months)
Duration of Response (DoR)	The time from the date of first response until date of disease progression or death in the absence of disease progression.	From time of first dose of HRS-1167 or Bevacizumab until the date of objective disease progression or death (up to 24 months)
Progression free Survival (PFS)	Progression-free survival is defined as the time from the start of treatment until the date of objective disease progression or death	From time of fist dose of HRS-1167 or Bevacizumab until the date of objective disease progression or death (up to 24 months)
Overall Survival (OS)	The time until death due to any cause.	From time of first dose of HRS-1167 or Bevacizumab until the date of death (up to 24 months)
Time To Response(TTR)	Time from C1D1 to complete or partial response, according to RECIST v1.1 criteria.	From time of first dose of HRS-1167 or Bevacizumab until the date of objective disease progression or death (up to 24 months)

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2024
• Primary Completion (Estimated): October 1, 2025
• Study Completion (Estimated): October 1, 2025

Study Registration Dates

• First Submitted: February 26, 2024
• First Submitted That Met QC Criteria: March 6, 2024
• First Posted (Actual): March 13, 2024

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 9, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Disease Attributes; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Recurrence; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: HRS-1167-201-Bev

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No