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

Overview

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.

Interventions

• Drug Disitamab Vedotin
  2.0 mg/kg IV every 2 weeks
• Drug Zimberelimab
  240mg IV every 2 weeks

Primary outcome measures

• Safety run-in ：Safety(adverse event) [Time frame: Up to approximately 2 years]
• Dose extension period ：Objective Response Rate (ORR) [Time frame: Up to approximately 2 years]

Secondary outcome measures (5)

• Objective Response Rate(ORR) [Time frame: Up to approximately 2 years]
• Duration of Response (DOR) [Time frame: Up to approximately 2 years]
• Disease Control Rate(DCR) [Time frame: Up to approximately 2 years]
• Progression-free survival (PFS), evaluated by the investigator [Time frame: Up to approximately 2 years]
• Overall survival (OS) [Time frame: Up to approximately 2 years]

Eligibility criteria

Inclusion criteria

• 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;
• Voluntarily agreed to participate in the study and signed an informed consent form.
• Female, age ≥ 18 years
• Expected survival ≥ 12 weeks
• Central laboratory confirmation of HER2 expression: IHC 1+, 2+, or 3+; subjects with IHC 2+ require testing for FISH.
• Central laboratory confirmation of PD-L1 expression
• Measurable disease according to RECIST 1.1 standard
• ECOG physical condition 0 or 1 point
• Adequate organ function, criteria should be met during the screening period

• ANC ≥1,500/µL
• platelet count ≥100,000/μL
• hemoglobin ≥9.0 g/dL
• 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
• CrCl ≥50 mL/min (measured by the Cockcroft-Gault formula as applicable, or 24-hour urine).
• ALT and AST ≤2.5× ULN without liver metastases or ≤5× ULN with liver metastases
• LVEF ≥>50%
• 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.
• Willingness and ability to comply with trial and follow-up procedure arrangements.

Exclusion criteria

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

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 12 centers

• The first affiliated hospital of bengbu medical college — Bengbu
• Beijing Obstetrics and Gynecology Hospital ,Capital Medical University — Beijing
• Chongqing University Cancer Hospital — Chongqing
• Guangxi Tumor Hospital — Nanning
• Hunan Cancer Hospital — Changsha
• Jiangxi Maternal and Child Health Hospital — Nanchang
• Liaoning Cancer Hospital & Institute — Shenyang
• Shandong Cancer Hospital & Institute — Jinan
• … and 4 more centers

Identifiers

NCT: NCT06155396 · RC48-C030

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗