A Study of RC48-ADC Combination With Zimberelimab Injection Therapies at Least First-line Platinum-containing Standard Therapy Failed With Recurrent or Metastatic Cervical Cancer

A Single-Arm, Open- Label, Multicenter Phase II Study of RC48-ADC in Combination With Zimberelimab Injection for the Treatment ,at Least First-line Platinum-containing Standard Therapy Failed in HER2-expressing Subject With Recurrent or Metastatic Cervical Cancer

This study will evaluate the efficacy,safety of RC48-ADC in Combination with Zimberelimab Injection for the Treatment ,at least first-line platinum-containing standard therapy failed in HER2-expressing subject with Recurrent or Metastatic Cervical Cancer

Study Overview

• Status: Recruiting
• Conditions: Cervical Cancer
• Intervention / Treatment: Drug: Disitamab Vedotin; Drug: Zimberelimab

Detailed Description

This is a Phase II, Single-Arm ,multicenter, open-label clinical trial designed to evaluate safety and efficacy of RC48-ADC in Combination with Zimberelimab Injection for the Treatment ,at least first-line platinum-containing standard therapy failed in HER2-expressing subject with Recurrent or Metastatic Cervical Cancer.The HER2-expressing is defined as: the HER2 IHC 3+ or 2+, or 1+.subjects with IHC 2+ require testing for FISH.

• Study Type: Interventional
• Enrollment (Estimated): 116
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jianmin Fang, Ph.D; Phone Number: +8610-58075763; Email: Jianminfang@hotmail.com

Study Locations

• China
  • Anhui
    • Bengbu, Anhui, China, 233000
      • Not yet recruiting
      • The first affiliated hospital of bengbu medical college
      • Contact: Yuzhi Li, M.D
  • Beijing
    • Beijing, Beijing, China, 100026
      • Not yet recruiting
      • Beijing Obstetrics and Gynecology Hospital ,Capital Medical University
      • Contact: Jinwei Miao, M.D
  • Chongqing
    • Chongqing, Chongqing, China, 400030
      • Not yet recruiting
      • Chongqing University Cancer Hospital
      • Contact: Ying Tang, M.D
  • Guangxi
    • Nanning, Guangxi, China, 530021
      • Not yet recruiting
      • Guangxi Tumor Hospital
      • Contact: Qingjie Zhang, M.D
  • Hunan
    • Changsha, Hunan, China, 410031
      • Not yet recruiting
      • Hunan Cancer Hospital
      • Contact: Keqiang Zhang, M.D.
  • Jiangxi
    • Nanchang, Jiangxi, China, 330008
      • Not yet recruiting
      • Jiangxi Maternal and Child Health Hospital
      • Contact: Meirong Liang, M.D
  • Liaoning
    • Shenyang, Liaoning, China, 110801
      • Not yet recruiting
      • Liaoning Cancer Hospital & Institute
      • Contact: Chunyan Wang, Ph.D
  • Shandong
    • Jinan, Shandong, China, 250117
      • Not yet recruiting
      • Shandong Cancer Hospital & Institute
      • Contact: Dapeng Li, M.D.
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Recruiting
      • Fudan University Shanghai Cancer Center
      • Contact: Xiahua Wu, Ph.D
  • Tianjin
    • Tianjin, Tianjin, China, 300181
      • Not yet recruiting
      • Tianjin Medical University Cancer Institute and Hospital
      • Contact: Ke Wang, M.D
  • Yunnan
    • Kunming, Yunnan, China, 650118
      • Not yet recruiting
      • Yunnan Cancer Hospital
      • Contact: Hongping Zhang, Ph.D
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310005
      • Not yet recruiting
      • Zhejiang Cancer Hospital
      • Contact: Xiaojuan Lv, M.D.

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. a)Patients with histologically confirmed HER2-expressing recurrent or metastatic cervical cancer who have failed at least 1 line of standard platinum-containing therapy ; b) Not suitable for surgery or radiotherapy;
2. Voluntarily agreed to participate in the study and signed an informed consent form.
3. Female, age ≥ 18 years
4. Expected survival ≥ 12 weeks
5. Central laboratory confirmation of HER2 expression: IHC 1+, 2+, or 3+; subjects with IHC 2+ require testing for FISH.
6. Central laboratory confirmation of PD-L1 expression
7. Measurable disease according to RECIST 1.1 standard
8. ECOG physical condition 0 or 1 point

9. Adequate organ function, criteria should be met during the screening period

   1. ANC ≥1,500/µL
   2. platelet count ≥100,000/μL
   3. hemoglobin ≥9.0 g/dL
   4. total bilirubin ≤1.5 × upper limit normal (ULN) OR direct bilirubin ≤ULN for subjects with total bilirubin >1.5 × ULN. Serum bilirubin ≤3× ULN for subjects with Gilbert's disease
   5. CrCl ≥50 mL/min (measured by the Cockcroft-Gault formula as applicable, or 24-hour urine).
   6. ALT and AST ≤2.5× ULN without liver metastases or ≤5× ULN with liver metastases
   7. LVEF ≥>50%
10. Female subjects should be surgically sterilised, post-menopausal or agree to use at least one medically approved contraceptive method during and for 6 months after the end of the study treatment period, must have had a negative blood pregnancy test within 7 days prior to study entry, and must be non-lactating.
11. Willingness and ability to comply with trial and follow-up procedure arrangements.

Exclusion Criteria:

1. Have central nervous system metastases and/or carcinomatous meningitis.
2. Received anti-tumour therapy or participated in another clinical study treatment within 4 weeks prior to the start of study treatment.
3. Toxicity due to previous antineoplastic therapy has not recovered to NCI-CTCAE (version 5.0) grade 0-1.
4. Major surgery with incomplete recovery within 4 weeks prior to start of study dosing.

5. Serum virology examination (based on the normal value of the research center) :

   1. HBsAg test results were positive, and HBV DNA copy number was positive;
   2. HCVAb test results were positive (HCV RNA PCR test results were negative only to be included in this study);
   3. HIVAb tested positive
6. Have received a live or live attenuated vaccine within 4 weeks prior to the start of study dosing; or plan to receive any vaccine during the study period
7. Grade 3 or higher heart failure
8. History of gastrointestinal perforation and/or fistula within the previous 6 months
9. Serious arterial/venous thrombotic event or cardiovascular accident within 1 year prior to study drug administration
10. Presence of active or progressive infection requiring systemic therapy, with severe infection within 4 weeks prior to first dose;
11. Active TB.
12. Presence of systemic disease not under stable control as judged by the investigator.
13. History of interstitial pneumonia, obstructive lung disease, drug-induced pneumonia, radiation pneumonia, idiopathic pneumonia or active pneumonia.
14. Clinically relevant pyelonephrosis cannot be alleviated by ureteral stents or percutaneous drainage.
15. Presence of active autoimmune disease requiring systemic therapy within 2 years prior to the start of study drug administration, allowing for relevant alternative therapy.
16. Other malignancy within 5 years prior to start of study drug administration.
17. Previous allogeneic haematopoietic stem cell transplantation.
18. Previous treatment with other Antibody-drug conjugateantibody-coupled drugs.
19. Known hypersensitivity to the drug vedicilizumab for injection and its components or to Zimberelimab injection and other monoclonal antibodies.
20. Have any other disease, metabolic abnormality, physical examination abnormality or laboratory test abnormality.
21. Estimated lack of patient adherence to participate in this clinical study.

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: Disitamab Vedotin + Zimberelimab; Disitamab Vedotin（RC48-ADC）with Zimberelimab arm	Drug: Disitamab Vedotin; 2.0 mg/kg IV every 2 weeks; Other Names: Disitamab Vedotin （RC48-ADC); Drug: Zimberelimab; 240mg IV every 2 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety run-in ：Safety(adverse event)	to evaluate safety including adverse event rate and adverse event grade.	Up to approximately 2 years
Dose extension period ：Objective Response Rate (ORR)	The objective response rate will be mainly analyzed by according to the RECIST 1.1 standard tumor evaluation by the investigator will be performed	Up to approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate(ORR)	The objective response rate will be mainly analyzed by according to the RECIST 1.1 standard tumor evaluation by the investigator will be performed	Up to approximately 2 years
Duration of Response (DOR)	DOR is defined as the time from the first documented objective response (CR or PR) to the first documented disease progression or death	Up to approximately 2 years
Disease Control Rate(DCR)	Proportion of patients whose tumors shrank or stabilized for a certain period of time	Up to approximately 2 years
Progression-free survival (PFS), evaluated by the investigator	Progression-free survival (PFS) refers to the time from the date of first administration to the first researcher's evaluation of disease progression or death (calculated by the event that occurred first). The disease progression will be evaluated by the researchers according to the RECIST 1.1 standard.	Up to approximately 2 years
Overall survival (OS)	Overall survival (OS) refers to the time from the date of first administration to the date of death of the subject.	Up to approximately 2 years

Collaborators and Investigators

• Sponsor: RemeGen Co., Ltd.
• Investigators: Study Director: Jianmin Fang, Ph.D, RemeGen Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): January 11, 2024
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: November 23, 2023
• First Submitted That Met QC Criteria: November 23, 2023
• First Posted (Actual): December 4, 2023

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 26, 2024
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Recurrent Cervical Cancer; Metastatic Cervical Cancer; HER2-expressing
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Uterine Cervical Neoplasms; Physiological Effects of Drugs; Immunologic Factors; Immunoconjugates; Disitamab vedotin
• Other Study ID Numbers: RC48-C030

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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