DV Combined With Cadonilimab in Subjects With HER2-expressing Gastric Cancer and Gastroesophageal Junction Adenocarcinoma After Progression on First-line Therapy

NCT06221748 | Recruiting Phase 2

• 1 other identifier: RC48-C035
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 12

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.

Conditions

Gastric Cancer; Gastroesophageal Junction Adenocarcinoma

Keywords

Gastric cancer; Gastroesophageal junction adenocarcinoma; HER2- expressing

Outcome Measures

Primary Outcomes (4)

• Objective remission rate (ORR) (Phase II)

  ORR assessed according to the evaluation criteria for the efficacy of solid tumors (RECIST 1.1)

  Up to approximately 2 years

• Percentage of Participants With Adverse Events (AEs)(Phase II)

  Number of participants with adverse effects of treatment. Frequency and severity of adverse effects of treatment as assessed by NCI CTCAE v5.0

  Up to approximately 2 years

• Progression-Free Survival(PFS) （IRC）（ Phase III)

  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)

  Up to approximately 2 years

• Overall Survival (OS)(Phase III)

  OS was defined as the time from the date of randomization to the date of death from any cause.

  Up to approximately 2 years

Secondary Outcomes (9)

• 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

• 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

Study Arms (3)

Disitamab Vedotin + Cadonilimab

EXPERIMENTAL

Disitamab Vedotin With Cadonilimab

Drug: Disitamab Vedotin Injection; Drug: Cadonilimab Injection

Disitamab Vedotin

EXPERIMENTAL

Disitamab Vedotin arm

Drug: Disitamab Vedotin Injection

Paclitaxel

EXPERIMENTAL

Paclitaxel Arm

Drug: Paclitaxel Injection

Interventions

Disitamab Vedotin Injection DRUG

Phase II and III study ：2.5mg/kg, intravenous infusion，D1, every 2 weeks

Also known as: DV,RC48

Disitamab Vedotin; Disitamab Vedotin + Cadonilimab

Cadonilimab Injection DRUG

Phase II and III study ：6.0mg/kg, intravenous infusion，D1, every 2 weeks.

Also known as: AK104, Cadonilimab Injection

Disitamab Vedotin + Cadonilimab

Paclitaxel Injection DRUG

Phase II and III study ：Calculate dosage based on body surface are,160mg/m2,intravenous infusion，D1,D8 every 3 weeks

Paclitaxel

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• Platelet count ≥ 90 × 109/L (no platelet transfusion or treatment with recombinant human thrombopoietin within 2 weeks before the test);
• Liver function (based on normal values at the Clinical Trials Center):
• Serum total bilirubin ≤ 1.5 times the upper limit of normal (ULN);
• Alanine aminotransferase (ALT) and Mentholatum aminotransferase (AST) ≤ 2.5 × ULN in the absence of hepatic metastases; ALT and AST ≤ 5 × ULN in the presence of hepatic metastases;
• Renal function (based on normal values at the Clinical Trials Center):

You may not qualify if:

• 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;
• Positive test result for Hepatitis C Antibody (HCVAb) (enrollment in the study is only possible if the PCR test result for HCV RNA is negative);
• Positive test result for human immunodeficiency virus antibody (HIVAb).；
• Serious arterial/venous or cardiovascular accidents, such as deep vein thrombosis ( except asymptomatic interstitial vein thrombosis which does not require special treatment), pulmonary embolism, cerebral infarction, cerebral hemorrhage, myocardial infarction, angina pectoris, etc., except for lacunar cerebral infarction, which is asymptomatic and does not require clinical intervention, have occurred in the last 6 months prior to the study drug administration;
• Tumor lesions with bleeding tendency (e.g., presence of active ulcerated tumor lesions with a positive fecal occult blood test, history of vomiting blood or black stools within 2 months prior to signing the informed consent form, risk of gastrointestinal hemorrhage in the judgment of the investigator, etc.), or receipt of blood transfusion 4 weeks prior to study drug administration;;
• The occurrence of an active or progressive infection requiring systemic treatment (trial drug may be initiated 2 weeks after completion of anti-infective therapy);

Sponsors & Collaborators

• RemeGen Co., Ltd.: lead

Study Sites (12)

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

RECRUITING

The First Affiliated Hospital of Xiamen University

Xiamen, Fujian, 361003, China

NOT YET RECRUITING

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, 150081, China

NOT YET RECRUITING

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, 450052, China

NOT YET RECRUITING

Hubei Cancer Hospital

Wuhan, Hubei, 430079, China

NOT YET RECRUITING

Hunan Cancer Hospital

Changsha, Hunan, 410031, China

RECRUITING

Xuzhou Central Hospital

Xuzhou, Jiangsu, 221009, China

RECRUITING

Shandong Cancer Hospital

Jinan, Shandong, 250117, China

RECRUITING

The Affiliated Hospital of Qingdao University

Qingdao, Shandong, 266003, China

NOT YET RECRUITING

Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200025, China

NOT YET RECRUITING

West China Hospital of Sichuan University

Chengdu, Sichuan, 610041, China

NOT YET RECRUITING

Yunnan Cancer Hospital

Kunming, Yunnan, 650118, China

RECRUITING

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

disitamab vedotin; Paclitaxel

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Jianmin Fang, Ph.D

  RemeGen Co., Ltd.

  STUDY DIRECTOR

Central Study Contacts

Jianmin Fang, Ph.D

CONTACT

+8610-58075763; Jianminfang@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2024
• First Posted: January 24, 2024
• Study Start: February 22, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: April 3, 2024

Record last verified: 2024-01

Locations

CN (12)