Gastric and Gastroesophageal Junction Carcinoma
Conditions
Brief summary
This is a Phase Ib/II, open-label, multicenter, randomized umbrella study in participants with advanced gastric carcinoma (GC) or gastroesophageal junction carcinoma (GEJC). The study is designed with the flexibility to open new treatment arms as new treatments become available, close existing treatment arms that demonstrate minimal clinical activity or unacceptable toxicity, and modify the participant population. Cohort 1 will enroll participants with inoperable locally advanced, metastatic, or advanced GC or GEJC, with adenocarcinoma confirmed as the predominant histology, who have not received prior systemic therapy for advanced or metastatic disease. Eligible participants will initially be randomly assigned to one of treatment arms (Stage 1). Participants who experience loss of clinical benefit or unacceptable toxicity during Stage 1 may be eligible to receive treatment with a different treatment combination (Stage 2). When a Stage 2 treatment combination is available, this will be introduced by amending the protocol.
Interventions
DRUGAtezolizumab
Atezolizumab is administered by IV infusion on Day 1 of each 21 day cycle. Treatment until progressive disease.
DRUGCapecitabine
Capecitabine is administered orally twice daily on Days 1-14 of each 21 day cycle. Treatment for up to six cycles.
DRUGOxaliplatin
Oxaliplatin is administered by IV infusion on Day 1 of each 21 day cycle. Treatment for up to six cycles.
DRUGTiragolumab
Tiragolumab is administered by IV infusion on Day 1 of each 21 day cycle.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
for Stage 1: * ECOG Performance Status of 0 or 1 * Inoperable locally advanced, metastatic, or advanced GC or GEJC, with adenocarcinoma confirmed as the predominant histology * No prior systemic treatment for advanced or metastatic disease * Life expectancy \>= 3 months, as determined by the investigator * Human epidermal growth factor receptor 2 (HER2)-negative tumors * Measurable disease according to RECIST v1.1 * Adequate hematologic and end-organ function * Patients without hepatitis B virus (HBV) infection at screening * Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening * Negative HIV test at screening * For women of childbearing potential: agreement to remain abstinent or use contraception, and agreement to refrain from donating eggs, as outlined for each specific treatment arm * For men: agreement to remain abstinent or use contraception, and agreement to refrain from donating sperm, as outlined for each specific treatment arm
Exclusion criteria
for Stage 1: * Prior treatment with CD137 agonists or immune checkpoint blockade therapies * Treatment with investigational therapy within 28 days prior to initiation of study treatment * Any contraindications to any of the study drugs of the chemotherapy regimen * Eligible only for the control arm * Patients with a signet ring cells dominant carcinoma * Symptomatic, untreated, or actively progressing CNS metastases * History of leptomeningeal disease * Active or history of autoimmune disease or immune deficiency * Significant cardiovascular disease within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina * History of malignancy other than GC or GEJC within 2 years prior to initiation of study treatment, with the exception of malignancies with a negligible risk of metastasis or death
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Up to 42.1 months | ORR was defined as the percentage of participants with a complete response (CR) or partial response (PR) on two consecutive occasions, ≥ 4 weeks apart during Stage 1, as determined by the investigator according to RECIST v1.1. CR was defined as the disappearance of all target or non-target lesions. Any pathological lymph nodes (whether target or non-target lesions) must have a reduction in short axis to \< 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters (SOD) of all target lesions, taking as reference the baseline SOD, in the absence of CR. Participants with missing or no response assessments were classified as non-responders. Percentages have been rounded off. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) After Randomization | From randomization to first occurrence of PD or death from any cause, whichever occurred first (up to 42.1 months) | PFS after randomization was defined as the time from randomization to the first occurrence of PD or death from any cause (whichever occurred first) in Stage 1, as determined by the investigator according to RECIST v1.1. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline) or unequivocal progression of existing non-target lesions. Additionally, the SOD must also demonstrate an absolute increase of ≥ 5 mm. PFS was censored at the day of the last tumor assessment for participants who did not die or did not have documented PD. Median PFS was estimated using the Kaplan-Meier (K-M) method. |
| Overall Survival (OS) After Randomization | From randomization to death from any cause (up to 42.1 months) | OS was defined as the time from randomization to death from any cause, regardless of stage. Participants who were still alive at the time of OS analysis were censored at the last date they were known to be alive. Median OS was estimated using the K-M method. |
| OS Rates at Specified Timepoints | At Months 6 and 12 | OS was defined as the time from randomization to death from any cause, regardless of stage. OS rate at 6 and 12 months was defined as the percentage of participants who did not experience death from any cause at these timepoints from randomization. OS rates at the specified timepoints were estimated using the K-M method. Percentages have been rounded off. |
| Duration of Response (DOR) | From first occurrence of CR or PR to PD or death from any cause, whichever occurred first (up to 42.1 months) | DOR was defined as time from the first occurrence of a documented objective response (OR), CR or PR to PD or death from any cause (whichever occurred first) in Stage 1, as determined by the investigator according to RECIST v1.1. CR was defined as disappearance of all target or non-target lesions. Any pathological lymph nodes (whether target/non-target lesions) must have a reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline) or unequivocal progression of existing non-target lesions. Additionally, the SOD must also demonstrate an absolute increase of ≥ 5 mm. DOR was censored at the day of the last tumor assessment for participants who did not die or did not have documented PD. Median DOR was estimated using the K-M method. |
| Disease Control Rate (DCR) | Up to 42.1 months | DCR was defined as percentage of participants with stable disease (SD) for ≥ 12 weeks or a CR or PR, as determined by the investigator according to RECIST v1.1. SD was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. CR was defined as the disappearance of all target or non-target lesions. Any pathological lymph nodes (whether target or non-target lesions) must have a reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline) or unequivocal progression of existing non-target lesions. Additionally, the SOD must also demonstrate an absolute increase of ≥ 5 mm. Percentages have been rounded off. |
| Number of Participants With Adverse Events (AEs) | Up to 42.1 months | An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. |
Countries
China
Contacts
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Participant flow
Recruitment details
A total of 40 participants with inoperable locally advanced, metastatic, or advanced gastric carcinoma (GC) or gastroesophageal junction carcinoma (GEJC), who had not received prior systemic therapy for advanced or metastatic disease, took part in the study at 11 investigative sites in China from 01 March 2022 to 04 September 2025.
Pre-assignment details
Participants in Stage 1 were randomized to receive either atezolizumab (atezo) in combination with capecitabine and oxaliplatin (CAPOX) (control arm), or atezolizumab in combination with CAPOX and tiragolumab (tira) (experimental arm). As pre-specified in the Protocol, the sponsor decided not to open the Stage 2 part of the study for enrollment.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 63.83 years STANDARD_DEVIATION 8.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 22 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 40 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 13 / 18 | 18 / 22 |
| other Total, other adverse events | 18 / 18 | 22 / 22 |
| serious Total, serious adverse events | 9 / 18 | 12 / 22 |
Outcome results
None listed