A Randomized，Multicenter, Open-Label，Phase II/III Study to Evaluate the Safety and Efficacy of Disitamab Vedotin Combined With Cadonilimab in Subjects With HER2-expressing Locally Advanced or Metastatic Gastric Cancer and Gastroesophageal Junction Adenocarcinoma Who Have Progressed on r First-line Therapy
Overview
- Phase
- Phase 2
- Intervention
- Disitamab Vedotin Injection
- Conditions
- Gastric Cancer
- Sponsor
- RemeGen Co., Ltd.
- Enrollment
- 90
- Locations
- 12
- Primary Endpoint
- Objective remission rate (ORR) (Phase II)
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
The purpose of this study is to evaluate the efficacy and safety of Disitamab Vedotin Combined with Cadonilimab in subjects with HER2-expressing locally advanced or metastatic gastric cancer and gastroesophageal junction adenocarcinoma after progression on first-line therapy.
Detailed Description
This is an open-label, randomized, multicenter, Phase II/III Study designed to evaluate safety and efficacy of Disitamab Vedotin Combined with Cadonilimab in subjects with HER2-expressing locally advanced or metastatic gastric cancer and gastroesophageal junction adenocarcinoma after progression on first-line therapy. This clinical study was divided into two parts, phase II and III.Part I: Phase II study primary objectives of the study are to evaluate the efficacy and safety of Disitamab Vedotin Combined with Cadonilimab versus Disitamab Vedotin versus paclitaxel in subjects with HER2-expressing locally advanced or metastatic gastric cancer and gastroesophageal junction adenocarcinoma after progression on first-line therapy. Part II: Phase III study primary objectives of the study are to evaluate the efficacy and safety of Disitamab Vedotin Combined with Cadonilimab versus paclitaxel in subjects with HER2-expressing locally advanced or metastatic gastric cancer and gastroesophageal junction adenocarcinoma after progression on first-line therapy. Tumor assessments, including radiological assessments by CT/MRI scans will be performed at Screening and subsequently every 6 weeks (±7 days) until disease progression, death, the start of new anticancer therapy, or patient's withdrawal of consent (whichever occurs first). All patients who discontinue treatment will be followed for survival every 3 months until death, lost to follow-up, withdrawal of consent for survival follow-up, or end of study (whichever comes first).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Voluntarily agreed to participate in the study and signed an informed consent form;
- •Age 18-75 years(both 18 and 75);
- •Expected survival ≥ 12 weeks
- •ECOG physical condition score of 0 or 1
- •Locally advanced or metastatic gastric adenocarcinoma (including adenocarcinoma of the gastroesophageal junction) confirmed by histology and/or cytology
- •Subjects will only have failed or been intolerant to prior standard first-line therapy (excluding paclitaxel), with no restriction on prior treatment with a PD-1/PD-L1 inhibitor.
- •Confirmation of HER2 (IHC 1+, 2+, or 3+) and PD-L1 expression: for Phase II enrolled subjects, results of investigator-confirmed HER2 and PD-L1 expression will be accepted; for Phase III enrolled subjects, HER2 and PD-L1 expression will be accepted only as results from the central laboratory.
- •Bone marrow function:
- •Hemoglobin ≥ 9 g/dL (no blood transfusion and no erythropoietin treatment within 2 weeks prior to the examination);
- •Absolute neutrophil count ≥ 1.5 × 109/L (must not receive granulocyte colony-stimulating factor treatment within 2 weeks prior to the examination)
Exclusion Criteria
- •Metastatic CNS and/or meningeal carcinomatosis；
- •prior treatment with any antibody-drug conjugate including Disitamab Vedotin For Injection; prior treatment with cardinolizumab
- •Prior anti-cancer therapy resulting in toxicity that has not recovered to CTCAE (version 5.0) ≤ Grade 1 (except for hair loss, hyperpigmentation, or other conditions that do not increase the risk of the subject's use of the drug determined by the investigators;
- •Radical radiotherapy within 3 months prior to study dosing; palliative radiotherapy 2 weeks prior to dosing is permitted, at a dose that meets local diagnostic criteria for palliative care and with radiotherapy coverage of less than 30% of the bone marrow area;
- •Prior major surgery within 4 weeks before study dose start and incomplete recovery
- •Received a live vaccine within 28 days prior to the start of the first study dose or plan to receive any vaccine during the study period
- •Third interstitial effusion associated with clinical symptoms or that requires symptomatic treatment;
- •Ongoing grade ≥2 sensorimotor or motoneuropathy;
- •serum virology (based on site normal values):
- •Positive Hepatitis B virus surface antigen (HBsAg) test result with a positive HBV DNA copy number;
Arms & Interventions
Disitamab Vedotin + Cadonilimab
Disitamab Vedotin With Cadonilimab
Intervention: Disitamab Vedotin Injection
Disitamab Vedotin + Cadonilimab
Disitamab Vedotin With Cadonilimab
Intervention: Cadonilimab Injection
Disitamab Vedotin
Disitamab Vedotin arm
Intervention: Disitamab Vedotin Injection
Paclitaxel
Paclitaxel Arm
Intervention: Paclitaxel Injection
Outcomes
Primary Outcomes
Objective remission rate (ORR) (Phase II)
Time Frame: Up to approximately 2 years
ORR assessed according to the evaluation criteria for the efficacy of solid tumors (RECIST 1.1)
Progression-Free Survival(PFS) （IRC）（ Phase III)
Time Frame: Up to approximately 2 years
PFS was defined as the time from random assignment to the onset of disease progression (as assessed by the IRC according to RECIST v1.1 criteria) or death (whichever event occurs first)
Percentage of Participants With Adverse Events (AEs)(Phase II)
Time Frame: Up to approximately 2 years
Number of participants with adverse effects of treatment. Frequency and severity of adverse effects of treatment as assessed by NCI CTCAE v5.0
Overall Survival (OS)(Phase III)
Time Frame: Up to approximately 2 years
OS was defined as the time from the date of randomization to the date of death from any cause.
Secondary Outcomes
- Type, incidence, relatedness, severity, and seriousness of AEs(Up to approximately 2 years)
- Progression-Free Survival(PFS)（investigator）(Phase II and Phase III)(Up to approximately 2 years)
- Overall Survival (OS)(Phase II)(Up to approximately 2 years)
- Objective remission rate (ORR) （investigator） (Phase III)(Up to approximately 2 years)
- Incidence of laboratory tests abnormalities(Up to follow-up period, approximately 2 years)
- Disease Control Rate (DCR) (Phase II and Phase III)(Until progression, assessed up to approximately 2 years)
- Duration of response (DoR) (Phase II and Phase III)(Until progression, assessed up to approximately 2 years)
- Incidence of ECG abnormalities(Up to follow-up period, approximately 2 years)
- Incidence of echocardiograms abnormalities(Up to approximately 2 years)