HER2-positive Advanced Gastric Cancer or Gastroesophageal Junction Adenocarcinoma
Conditions
Brief summary
This study will assess the efficacy and safety of SHR-A1811 compared with treatment chosen by the investigator in participants with HER2-positive (defined as immunohistochemistry \[IHC\] 3+ or IHC 2+/in situ hybridization \[ISH\]+) gastric or GEJ adenocarcinoma (based on \[American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) guidelines who have progressed on or after a first-line anti-HER2 therapy-containing regimen.
Interventions
DRUGSHR-A1811
SHR-A1811 6.4 mg/kg IV infusion every 3 weeks on Day 1 of each 21-day cycle
DRUGRamucirumab / Paclitaxel/ Docetaxel/ Irinotecan
Ramucirumab 8mg/kg，D 1,15 + Paclitaxel 80mg/m2，D1,8,15，Q4W; Paclitaxel 80mg/m2，D1,8,15，Q4W; Docetaxel 75mg/m2，D1，Q3W; Irinotecan 150mg/m2，D1，Q2W.
Sponsors
Jiangsu HengRui Medicine Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18-75 years old, male and female; 2. Histologically or cytologically confirmed gastric or gastroesophageal junction adenocarcinoma, and unresectable locally advanced or metastatic disease 3. Prior anti-HER-2 containing treatment 4. Progression on or after first-line standard treatment (Prior neoadjuvant or adjuvant therapy can be counted as a line of therapy if the subject progressed on or within 6 months of completing neoadjuvant or adjuvant therapy); 5. Centrally confirmed HER2-positive (IHC 3+ or IHC 2+ and evidence of HER2 amplification by ISH) as classified by ASCO-CAP on a tumor biopsy 6. At least one measurable lesion according to the solid tumor response Evaluation Criteria (RECIST 1.1); 7. ECOG: 0-1; 8. Expected survival ≥12 weeks; 9. Good blood reserve and liver, kidney and coagulation function; 10. Willing to provide informed consent for study participation.
Exclusion criteria
1. Receive the last dose of anti-cancer therapy(including chemotherapy, radiotherapy, biological therapy, targeted therapy or immunotherapy) within 4 weeks, prior to the first dose; 2. Known allergies to monoclonal antibodies and inactive ingredients of this product, and allergies to paclitaxel, docetaxel, and irinotecan concurrently; 3. The toxicity of prior anti-tumor therapy did not recover to the level specified by CTCAE v5.0 grade evaluation ≤ Grade 1 or inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | Time from date of randomization until death (due to any cause), up to approximately 42 months | defined as the time from date of randomization until death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | From start of treatment to date of documented disease progression, up to approximately 42 months | defined as the proportion of participants who achieve a best response of complete response (CR) or partial response (PR) using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) criteria as assessed by Investigator. |
| Duration of response (DoR) | Time from initial response (CR or PR) to date of documented disease progression or death (due to any cause) whichever occurs first, up to approximately 42 months | defined time from the initial response (CR or PR) until documented tumor progression or death from any cause and based on Investigator assessment. |
| Disease control rate (DCR) | From start of treatment to date of documented disease progression, up to approximately 42 months | defined as the proportion of participants who achieved CR, PR, or stable disease (SD) for a minimum of 6 weeks during study treatment, based on Investigator assessment. |
| Progression-free survival (PFS) | Time from date of randomization until first objective radiographic disease progression or death (due to any cause) whichever occurs first, up to approximately 42 months | defined as the time from date of randomization until first objective radiographic tumor progression or death from any cause, based on Investigator assessment. |
| Immunogenicity indicators of SHR-A1811: including anti-SHR-A1811 antibodies (ADA and neutralizing antibodies) | approximately 42 months | — |
| Serum concentrations of SHR-A1811 toxin-binding antibodies and free toxin SHR169265 | approximately 42 months | — |
| AE and SAE | From time subjects signs informed consent form up to 40 days after last study dose | Adverse events will be graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events Version 5.0. |
Countries
China
Contacts
Primary ContactYang Wu
Outcome results
None listed