Gastroesophageal Adenocarcinoma
Conditions
Keywords
Locally Advanced Resectable Gastroesophageal Adenocarcinoma, Gastroesophageal Junction, Neoadjuvant Treatment, Perioperative Treatment, Gastric cancer, Immune checkpoint inhibitors, Chemotherapy
Brief summary
GEMINI-PeriOp GC study will assess the safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity of novel agents or novel combinations as perioperative treatment in participants with locally advanced resectable gastric, gastroesophageal junction (GEJ), or esophageal adenocarcinoma who have not received previous treatment for the disease.
Detailed description
This Phase II, open-label, multi-drug, multi-center platform study consists of individual sub-studies, each allows the assessment of multiple novel agents or novel combinations. Participants will be assigned across 3 sub-studies, to have sufficient evaluable participants of the confirmed recommended dose by Safety Review Committee (SRC) for study intervention in each corresponding sub-study.
Interventions
DRUGAZD0901
AZD0901 will be administered as an IV infusion.
DRUGRilvegostomig
Rilvegostomig will be administered as an IV infusion.
T-DXd will be administered as an IV infusion.
DRUGCapecitabine
Capecitabine (Fluoropyrimidine) will be administered orally as chemotherapy standard of care.
DRUG5-Fluorouracil (5-FU)
5-FU (Fluoropyrimidine) will be administered as an IV infusion as chemotherapy standard of care.
FLOT (5-FU, leucovorin, oxaliplatin, and docetaxel) Chemotherapy will be administered as an IV infusion.
Sponsors
AstraZeneca
Parexel
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically documented gastric, GEJ, or esophageal adenocarcinoma with resectable disease * Participants who are CLDN18.2-positive and HER2-negative in Sub-study 1 or HER2-positive in Sub-study 2; no specific requirements for Sub-study 3 * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Adequate organ and bone marrow function * Body weight \> 35 kg
Exclusion criteria
* Participants had any prior anti-cancer treatment or surgery for the current gastric, GEJ, or esophageal cancer. * Active or prior documented autoimmune or inflammatory disorders requiring systemic treatment with steroids or other immunosuppressive treatment * Central nervous system (CNS) pathology * Uncontrolled infections * Participants with history of (non-infectious) interstitial lung disease (ILD)/pneumonitis, current ILD/pneumonitis, or suspected ILD/pneumonitis * History of another primary malignancy * Participants with any known or suspicious distant metastasis * Uncontrolled hepatitis B and/or chronic or active hepatitis B * Current or prior use of immunosuppressive medication within 14 days before the first dose of study intervention
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with adverse events (AEs) and serious adverse events (SAEs) | Until sub-study completion, up to 38 months | To assess the safety and tolerability of perioperative treatment. |
| Percentage of participants with pathological complete response (pCR) | Until sub-study completion, up to 38 months | pCR is defined as no viable cancer cells, including lymph nodes after complete evaluation in the resected gastric, GEJ, or esophageal cancer specimen and all sampled regional lymph nodes following neoadjuvant treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Surgery completion rate as planned | Until sub-study completion, up to 38 months | Surgery completion rate (including R0 and R1) as planned is defined as the percentage of participants who received intended gastrectomy or gastroesophagectomy as planned. |
| R0 resection (complete resection) rate as planned | Until sub-study completion, up to 38 months | R0 resection (complete resection) rate as planned is the percentage of participants who received gastrectomy or gastroesophagectomy and had a confirmed margin-negative resection as planned. |
| Percentage of participants with tumor downstaging | Until sub-study completion, up to 38 months | Tumor downstaging is defined as the lowering of the primary tumor (T) and/or regional lymph nodes (N) from pre-neoadjuvant clinical staging (pre-cTN) to post-neoadjuvant clinical staging (post-cTN) and to postoperative pathological staging (ypTN). |
| Event-free survival (EFS) | Until sub-study completion, up to 38 months | EFS is defined as the time from the first dose of study intervention to documented Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) or non-RECIST 1.1 disease progression that precludes radical surgery or requires non-protocol therapy during the neoadjuvant through surgery period, or to documented RECIST 1.1 or biopsy-confirmed non-RECIST 1.1 recurrence or progression of disease during the adjuvant period, or death due to any cause at any time. |
| Disease-free survival (DFS) | Until sub-study completion, up to 38 months | DFS is defined as the time elapsed from the date of the first post-surgery scan (ie, Adjuvant Baseline scan) until the date of first evidence of disease recurrence as determined by Investigator using RECIST 1.1 assessment (local or distant), or death due to any cause, whichever occurs first. |
| Objective response rate (ORR) | Until sub-study completion, up to 38 months | ORR is defined as the percentage of participants who have a CR or PR as determined by Investigator using RECIST 1.1 at their latest assessment prior to surgery. |
| Overall survival (OS) | Until sub-study completion, up to 38 months | OS is defined as the time from the first dose of the study intervention until the date of death due to any cause regardless of whether participant withdraws from treatment or receives another anti-cancer therapy. |
| Serum concentrations of study interventions | Until sub-study completion, up to 38 months | To assess the serum concentrations of study interventions in participants receiving perioperative treatment. |
| Number of participants with positive anti-drug antibodies (ADA) | Until sub-study completion, up to 38 months | To assess the immunogenicity of study interventions in participants receiving perioperative treatment. |
Countries
Canada, China, Georgia, Italy, Japan, Poland, Spain, Taiwan, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed