None listed
Conditions
Interventions
Drug : Neoadjuvant treatment will be administered beginning on Day 1 of Cycle 1 and will be administered for three times 3-week cycles.
Following surgery,
For cohort A: patients will receive adjuvan
Sponsors
Samsung Medical Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of fully informed consent prior to any study specific procedures. 2. Patients must be = 19 years of age 3. Body weight > 30kg 4. Has a Pathologically documented adenocarcinoma of gastric or gastroesophageal junction with HER2 IHC results. 5. In initial Cohort, HER2 positive (HER2 IHC 3+ or HER2 IHC 2+/ISH positive)) 6. Locally advanced unresectable disease by physician’s discretion (ex. cT4 or bulky Nx node or localized peritoneal seeding) No evident distant organ metastasis. 7. ECOG performance status PS 0-1 with no deterioration between screening and the first dose of study treatment. 8. Has LVEF = 50% by either echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 days before treatment 9. Has measurable target disease assessed by the Investigator based on RECIST version 1.1. 10. Has adequate organ and bone marrow, liver and renal function within 14 days before treatment Note: Transfusion (red blood cell or platelet) or G-CSF administration is not allowed within 14 days prior to the day on which bone marrow function is assessed, or at any time after this day and prior to C1D1. -Hemoglobin = 9.0 g/dL (=8.0 g/dL in GC Indications) -Platelet count =100 x 109/L -Absolute neutrophil count (ANC) = 1.5 x 109/L -Total bilirubin = 1.5 ULN if no liver metastases 45ml/min in Rilvegostomig) as determined by Cockcroft Gault (using actual body weight) -International normalised ratio or Prothrombin time and either partial thromboplastin or activated partial thromboplastin time = 1.5 × ULN 11. Female patients must be using a highly effective method of contraception (refer to the restrictions on P45) during the clinical trial and for 7 months after permanent discontinuation of the study drug. There must be evidence that patients are not breastfeeding, have a negative pregnancy test, or not of childbearing potential by meeting one of the following criteria at screening: a. Post-menopausal women defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatment. b. Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy, but not tubal ligation. c. Amenorrhoeic for 12 months and serum follicle-stimulating hormone (FSH), lutenizing hormone (LH) and plasma oestradiol levels in the postmenopausal range for the institution More detailed information is provided in Appendix G (Definition and accepted contraception for women of childbearing age). Also female participants must not breastfeed and must not donate/retrieve ova from screening to 60 days post last dose 12. Non-sterilized male patients who are sexually active with a female partner of childbearing potential must use a condom with spermicide from screening to 4 months after the final dose of IMP. Complete heterosexual abstinence for the duration of the study and drug washout period is an acceptable contraceptive method if it is in line with the patient’s usual lifestyle (consideration must be made to the duration of the clinical trial); however, periodic or occasional abstinence, the rhythm method, and the withdrawal method are not acceptable.
Exclusion criteria
Exclusion criteria: 1. Patients with evident peritoneal metastasis (including tumor cells in peritoneal fluid) or distant metastasis 2. Known dihydropyrimidine dehydrogenase (DPD) enzyme deficiency based on either local or central laboratory testing. Central laboratory testing will be available for patients where testing is SOC and with unknown DPD status. 3. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, uncontrolled hypertension, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs, or compromise the ability of the participant to give written informed consent. 4. Unresolved toxicities of = Grade 2 (Common Terminology Criteria for Adverse Events [CTCAE] v5.0) from prior therapy (excluding vitiligo, alopecia, endocrine disorders that are controlled with replacement hormone therapy, asymptomatic laboratory abnormalities). 5. History of organ transplant. 6. Active primary immunodeficiency/active infectious diseases. Active or prior documented autoimmune or inflammatory disorders (including IBD [e.g. Crohn’s disease, ulcerative colitis or diverticulitis], SLE, sarcoidosis syndrome, tuberculosis, Wegener syndrome, myasthenia gravis, Graves’ disease, rheumatoid arthritis, hypophysitis, uveitis, at screening, , that requires use of immunosuppressives, glomerulonephritis, nephritic syndrome, Fanconi Syndrome or renal tubular acidosis within the past 2 years prior to the start of treatment. The following are exceptions to this criterion: - Subjects with vitiligo or alopecia, hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement or psoriasis not requiring systemic treatment; patients with coeliac disease controlled by diet alone and patients without active disease in the last 5 years may be included after consultation with Chief Investigator. -HbsAg carrier without active viral infection and under entecavir prophylaxis will be allowed. 7. History of (non-infectious) ILD/pneumonitis, current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening. 8. Active hepatitis B (HBV surface antigen [HBsAg] positive) or active hepatitis C. Virus testing is not essential for clinical trial feasiblity assessment. Patients who have had or have resolved HBV infection or HCV infection in the past may participate in clinical trials. Note: For HBsAg-, patient needs to be >6 months off antiviral treatment 9. Participants with past or resolved HBV infection are eligible only if they meet all of the following criteria*: • Anti-HBc (+) (IgG or total Ig), • HBV DNA undetectable, • Absence of cirrhosis or fibrosis on prior imaging or biopsy, • Absence of HCV co-infection or history of HCV co-infection. • Access to a local Hepatitis B expert during and after the study. Such participants should be closely monitored for HBV reactivation. Consideration should be given to exclusion of all participants with HBV infection if comparator or combination study treatments are associated with a high risk of HBV infection reactivation are incompatible with anti-viral medications. 10. Known to have tested positive for human immunodeficiency virus (HIV) (positive HIV 1/2 antibodies) or active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| AEs/SAEs | — |
Secondary
| Measure | Time frame |
|---|---|
| To assess secondary measures of clinical efficacy (pCR, R0 resection rate, OS, EFS, Duration of response, ORR) | — |
Countries
Korea, Republic of
Contacts
Public ContactJeeyun Lee
Samsung Medical Center
Outcome results
None listed