Clinical trial NCT06155396: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Cervical Cancer
Keywords: HER2-expressing
Recurrent Cervical Cancer
Metastatic Cervical Cancer
Lead sponsor: RemeGen Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-12-04
Enrollment: 116
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Safety run-in ：Safety(adverse event)
timeFrame: Up to approximately 2 years
measure: Dose extension period ：Objective Response Rate (ORR)
timeFrame: Up to approximately 2 years
Secondary outcomes:
measure: Objective Response Rate(ORR)
timeFrame: Up to approximately 2 years
measure: Duration of Response (DOR)
timeFrame: Up to approximately 2 years
measure: Disease Control Rate(DCR)
timeFrame: Up to approximately 2 years
measure: Progression-free survival (PFS), evaluated by the investigator
timeFrame: Up to approximately 2 years
measure: Overall survival (OS)
timeFrame: Up to approximately 2 years
Other outcomes:
Locations:
city: Bengbu
country: China
facility: The first affiliated hospital of bengbu medical college
state: Anhui
city: Beijing
country: China
facility: Beijing Obstetrics and Gynecology Hospital ,Capital Medical University
state: Beijing
city: Chongqing
country: China
facility: Chongqing University Cancer Hospital
state: Chongqing
city: Nanning
country: China
facility: Guangxi Tumor Hospital
state: Guangxi
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Nanchang
country: China
facility: Jiangxi Maternal and Child Health Hospital
state: Jiangxi
city: Shenyang
country: China
facility: Liaoning Cancer Hospital & Institute
state: Liaoning
city: Jinan
country: China
facility: Shandong Cancer Hospital & Institute
state: Shandong
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
state: Tianjin
city: Kunming
country: China
facility: Yunnan Cancer Hospital
state: Yunnan
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
Study officials:
affiliation: RemeGen Co., Ltd.
name: Jianmin Fang, Ph.D
role: STUDY_DIRECTOR
References: