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NCT05251948

An Umbrella Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Gastric or Gastroesophageal Junction Carcinoma

Terminated Phase 1, PHASE2 Results posted Last updated 15 April 2026
What this trial tests

Phase 1, PHASE2 trial testing Atezolizumab in Gastric and Gastroesophageal Junction Carcinoma in 40 participants. Terminated before completion.

Timeline
1 March 2022
Primary endpoint
4 September 2025
4 September 2025

Quick facts

Lead sponsorHoffmann-La Roche
PhasePhase 1, PHASE2
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment40
Start date1 March 2022
Primary completion4 September 2025
Estimated completion4 September 2025
Sites11 locations across China

Drugs / interventions tested

Conditions studied

Sponsor

Hoffmann-La Roche — full company profile →

Who can join

18 and older, any sex, with Gastric and Gastroesophageal Junction Carcinoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Objective Response Rate (ORR) Primary · 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 w

GroupValue95% CI
Atezo + CAPOX55.630.76 – 78.47
Atezo + CAPOX + Tira40.920.71 – 63.65
Progression-free Survival (PFS) After Randomization Secondary · 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 di

GroupValue95% CI
Atezo + CAPOX9.516.97 – 13.08
Atezo + CAPOX + Tira6.654.93 – 9.20
Overall Survival (OS) After Randomization Secondary · 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.

GroupValue95% CI
Atezo + CAPOX20.8511.04 – 26.28
Atezo + CAPOX + Tira12.676.60 – 15.67
OS Rates at Specified Timepoints Secondary · 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.

Month 6
GroupValue95% CI
Atezo + CAPOX93.7581.89 – 100.00
Atezo + CAPOX + Tira86.3672.02 – 100.00
Month 12
GroupValue95% CI
Atezo + CAPOX68.7546.04 – 91.46
Atezo + CAPOX + Tira50.0029.11 – 70.89
Duration of Response (DOR) Secondary · 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

GroupValue95% CI
Atezo + CAPOX10.385.62 – 20.37
Atezo + CAPOX + Tira8.084.14 – 21.98
Disease Control Rate (DCR) Secondary · 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.

GroupValue95% CI
Atezo + CAPOX77.852.36 – 93.59
Atezo + CAPOX + Tira72.749.78 – 89.27
Number of Participants With Adverse Events (AEs) Secondary · 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.

GroupValue95% CI
Atezo + CAPOX18
Atezo + CAPOX + Tira22

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 42.1 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Atezo + CAPOX
Serious: 9/18 (50%)
Deaths: 13/18
Atezo + CAPOX + Tira
Serious: 12/22 (55%)
Deaths: 18/22

Serious adverse events (28 terms)

ReactionSystemAtezo + CAPOXAtezo + CAPOX + Tira
PneumoniaInfections and infestations
AnaemiaBlood and lymphatic system disorders
Febrile neutropeniaBlood and lymphatic system disorders
Acute coronary syndromeCardiac disorders
Immune-mediated myocarditisCardiac disorders
Lymphocytic hypophysitisEndocrine disorders
Gastrointestinal obstructionGastrointestinal disorders
IleusGastrointestinal disorders
Immune-mediated enterocolitisGastrointestinal disorders
Intestinal obstructionGastrointestinal disorders
Small intestinal obstructionGastrointestinal disorders
Upper gastrointestinal haemorrhageGastrointestinal disorders
VomitingGastrointestinal disorders
Autoimmune hepatitisHepatobiliary disorders
Cholecystitis acuteHepatobiliary disorders
Hepatic failureHepatobiliary disorders
JaundiceHepatobiliary disorders
COVID-19Infections and infestations
COVID-19 pneumoniaInfections and infestations
Herpes zosterInfections and infestations
Alanine aminotransferase increasedInvestigations
Decreased appetiteMetabolism and nutrition disorders
HypoalbuminaemiaMetabolism and nutrition disorders
Pain in extremityMusculoskeletal and connective tissue disorders
Altered state of consciousnessNervous system disorders
Other adverse events (90 terms — click to expand)

ReactionSystemAtezo + CAPOXAtezo + CAPOX + Tira
AnaemiaBlood and lymphatic system disorders
Neutrophil count decreasedInvestigations
Platelet count decreasedInvestigations
Aspartate aminotransferase increasedInvestigations
White blood cell count decreasedInvestigations
NauseaGastrointestinal disorders
HypokalaemiaMetabolism and nutrition disorders
VomitingGastrointestinal disorders
Weight decreasedInvestigations
Alanine aminotransferase increasedInvestigations
HypoalbuminaemiaMetabolism and nutrition disorders
PyrexiaGeneral disorders
Decreased appetiteMetabolism and nutrition disorders
Abdominal painGastrointestinal disorders
COVID-19Infections and infestations
Blood bilirubin increasedInvestigations
Blood lactate dehydrogenase increasedInvestigations
ProteinuriaRenal and urinary disorders
RashSkin and subcutaneous tissue disorders
HypothyroidismEndocrine disorders
ConstipationGastrointestinal disorders
AstheniaGeneral disorders
Gamma-glutamyltransferase increasedInvestigations
Lymphocyte count decreasedInvestigations
HypoaesthesiaNervous system disorders
HaematuriaRenal and urinary disorders
PruritusSkin and subcutaneous tissue disorders
Iron deficiency anaemiaBlood and lymphatic system disorders
DiarrhoeaGastrointestinal disorders
Ill-defined disorderGeneral disorders
COVID-19 pneumoniaInfections and infestations
PneumoniaInfections and infestations
Upper respiratory tract infectionInfections and infestations
Urinary tract infectionInfections and infestations
Infusion related reactionInjury, poisoning and procedural complications
Alpha hydroxybutyrate dehydrogenase increasedInvestigations
Blood alkaline phosphatase increasedInvestigations
Blood corticotrophin decreasedInvestigations
Blood follicle stimulating hormone increasedInvestigations
Blood luteinising hormone decreasedInvestigations

Most-reported serious reactions: Pneumonia, Anaemia, Febrile neutropenia, Acute coronary syndrome, Immune-mediated myocarditis, Lymphocytic hypophysitis, Gastrointestinal obstruction, Ileus.

Data from ClinicalTrials.gov NCT05251948 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Exploiting innate immunity for cancer immunotherapy.
    Yi M, Li T, Niu M, Mei Q, et al · · 2023 · cited 151× · PMID 38008741 · DOI 10.1186/s12943-023-01885-w
  2. Co-inhibition of TIGIT and PD-1/PD-L1 in Cancer Immunotherapy: Mechanisms and Clinical Trials.
    Chu X, Tian W, Wang Z, Zhang J, et al · · 2023 · cited 147× · PMID 37291608 · DOI 10.1186/s12943-023-01800-3
  3. Anti-TIGIT therapies for solid tumors: a systematic review.
    Rousseau A, Parisi C, Barlesi F. · · 2023 · cited 111× · PMID 36933320 · DOI 10.1016/j.esmoop.2023.101184
  4. Update in TIGIT Immune-Checkpoint Role in Cancer.
    Annese T, Tamma R, Ribatti D. · · 2022 · cited 40× · PMID 35656508 · DOI 10.3389/fonc.2022.871085
  5. Advances in molecular biomarkers research and clinical application progress for gastric cancer immunotherapy.
    Cai H, Li M, Deng R, Wang M, et al · · 2022 · cited 35× · PMID 36042469 · DOI 10.1186/s40364-022-00413-0
  6. Emergence of the CD226 Axis in Cancer Immunotherapy.
    Conner M, Hance KW, Yadavilli S, Smothers J, et al · · 2022 · cited 30× · PMID 35812451 · DOI 10.3389/fimmu.2022.914406
  7. Tiragolumab (Anti-TIGIT) in SCLC: Skyscraper-02, a Towering Inferno.
    Brazel D, Ou SI, Nagasaka M. · · 2023 · cited 22× · PMID 36636263 · DOI 10.2147/lctt.s379389
  8. Killer instincts: natural killer cells as multifactorial cancer immunotherapy.
    Nersesian S, Carter EB, Lee SN, Westhaver LP, et al · · 2023 · cited 8× · PMID 38090565 · DOI 10.3389/fimmu.2023.1269614

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