Treatment for recurrent or metastatic cervical cancer using RC48-ADC and Zimberelimab

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 is testing a new combination treatment of RC48-ADC and Zimberelimab for patients with recurrent or metastatic cervical cancer that has HER2 expression and hasn't responded to previous platinum-based therapies.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 116 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: RemeGen Co., Ltd. (Industry-sponsored)
• Drugs / interventions: vedicilizumab, Zimberelimab, radiation
• Locations: 12 sites (Bengbu, Anhui and 11 other locations)
• Trial ID: NCT06155396 on ClinicalTrials.gov

What this trial studies

This Phase II, single-arm, multicenter, open-label clinical trial aims to evaluate the safety and efficacy of RC48-ADC in combination with Zimberelimab injection for patients with HER2-expressing recurrent or metastatic cervical cancer who have failed at least one line of platinum-containing therapy. The study will include patients with confirmed HER2 expression and measurable disease, assessing their response to the treatment. Participants will be monitored for safety and treatment outcomes throughout the trial.

Who should consider this trial

Good fit: Ideal candidates are women aged 18 and older with histologically confirmed HER2-expressing recurrent or metastatic cervical cancer who have failed at least one line of platinum-containing therapy.

Not a fit: Patients who have not been diagnosed with HER2-expressing cervical cancer or those who are suitable for surgery or radiotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with recurrent or metastatic cervical cancer who have limited treatment alternatives.

How similar studies have performed: Other studies have shown promising results with similar approaches targeting HER2 in cervical cancer, indicating potential for success in this trial.

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.

Where this trial is running

Bengbu, Anhui and 11 other locations

• The first affiliated hospital of bengbu medical college — Bengbu, Anhui, China (Not_yet_recruiting)
• Beijing Obstetrics and Gynecology Hospital ,Capital Medical University — Beijing, Beijing Municipality, China (Not_yet_recruiting)
• Chongqing University Cancer Hospital — Chongqing, Chongqing Municipality, China (Not_yet_recruiting)
• Guangxi Tumor Hospital — Nanning, Guangxi, China (Not_yet_recruiting)
• Hunan Cancer Hospital — Changsha, Hunan, China (Not_yet_recruiting)
• Jiangxi Maternal and Child Health Hospital — Nanchang, Jiangxi, China (Not_yet_recruiting)
• Liaoning Cancer Hospital & Institute — Shenyang, Liaoning, China (Not_yet_recruiting)
• Shandong Cancer Hospital & Institute — Jinan, Shandong, China (Not_yet_recruiting)
• Fudan University Shanghai Cancer Center — Shanghai, Shanghai Municipality, China (Recruiting)
• Tianjin Medical University Cancer Institute and Hospital — Tianjin, Tianjin Municipality, China (Not_yet_recruiting)
• Yunnan Cancer Hospital — Kunming, Yunnan, China (Not_yet_recruiting)
• Zhejiang Cancer Hospital — Hangzhou, Zhejiang, China (Not_yet_recruiting)

Study contacts

• Study coordinator: Jianmin Fang, Ph.D

Conditions Cervical Cancer; HER2-expressing; Recurrent Cervical Cancer; Metastatic Cervical Cancer