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NCT03342937

KeyLargo: Pembrolizumab + Oxaliplatin + Capecitabine in Gastric Cancer

Completed Phase 2 Results posted Last updated 13 March 2024
What this trial tests

Phase 2 trial testing Oxaliplatin+Capecitabine+Pembrolizumab in Gastric Cancer in 36 participants. Completed in 6 February 2023.

Timeline
11 January 2018
Primary endpoint
6 February 2023
6 February 2023

Quick facts

Lead sponsorDuke University
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment36
Start date11 January 2018
Primary completion6 February 2023
Estimated completion6 February 2023
Sites7 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Duke University

Who can join

18 and older, any sex, with Gastric Cancer or Esophagus Cancer. 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.

Months of Progression-free Survival (PFS) Primary · Up to 44 months

PFS measured from study entry until documented progression or death from any cause. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression. Patients who have not experienced progression will be censored at the date of the last radiographic assessment. The median

GroupValue95% CI
Oxaliplatin + Capecitabine + Pembrolizumab7.65.8 – 11.2
Response Rate as Measured by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Secondary · Up to 44 months

Response rate is calculated as the number of people with a complete response or partial response, divided by the total number of people treated. Complete response is defined as disappearance of all target lesions. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

GroupValue95% CI
Oxaliplatin + Capecitabine + Pembrolizumab0.760. – 0.90
Months of Overall Survival Secondary · Up to 44 months

Overall survival is the amount of time subjects live since starting the study.

GroupValue95% CI
Oxaliplatin + Capecitabine + Pembrolizumab1611.6 – 24.3

Adverse events — posted to ClinicalTrials.gov

Time frame: From the first dose of study drug through 30 days after the last dose of study drug (up to 44 months).. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Oxaliplatin + Capecitabine + Pembrolizumab
Serious: 17/36 (47%)
Deaths: 26/36

Serious adverse events (24 terms)

ReactionSystemOxaliplatin + Capecitabine…
ColitisGastrointestinal disorders
VomitingGastrointestinal disorders
Colonic obstructionGastrointestinal disorders
DiarrheaGastrointestinal disorders
DysphagiaGastrointestinal disorders
NauseaGastrointestinal disorders
DehydrationMetabolism and nutrition disorders
HyperglycemiaMetabolism and nutrition disorders
Thromboembolic eventVascular disorders
Pericardial tamponadeCardiac disorders
Sinus tachycardiaCardiac disorders
Abdominal painGastrointestinal disorders
AscitesGastrointestinal disorders
ConstipationGastrointestinal disorders
Sudden death NOSGeneral disorders
Device related infectionInfections and infestations
Enterocolitis infectiousInfections and infestations
Infections and infestations - Other, SpecifyInfections and infestations
Lung infectionInfections and infestations
MeningitisInfections and infestations
SepsisInfections and infestations
Aspartate aminotransferase increasedInvestigations
Bone painMusculoskeletal and connective tissue disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
Other adverse events (124 terms — click to expand)

ReactionSystemOxaliplatin + Capecitabine…
NauseaGastrointestinal disorders
AnorexiaMetabolism and nutrition disorders
AnemiaBlood and lymphatic system disorders
FatigueGeneral disorders
DiarrheaGastrointestinal disorders
Peripheral sensory neuropathyNervous system disorders
Neutrophil count decreasedInvestigations
HypoalbuminemiaMetabolism and nutrition disorders
Palmar-plantar erythrodysesthesia syndromeSkin and subcutaneous tissue disorders
VomitingGastrointestinal disorders
Weight lossInvestigations
White blood cell decreasedInvestigations
DehydrationMetabolism and nutrition disorders
HyperglycemiaMetabolism and nutrition disorders
HypokalemiaMetabolism and nutrition disorders
HypertensionVascular disorders
DysphagiaGastrointestinal disorders
Blood bilirubin increasedInvestigations
InsomniaPsychiatric disorders
Allergic rhinitisRespiratory, thoracic and mediastinal disorders
CoughRespiratory, thoracic and mediastinal disorders
Thromboembolic eventVascular disorders
BloatingGastrointestinal disorders
ConstipationGastrointestinal disorders
DyspepsiaGastrointestinal disorders
Mucositis oralGastrointestinal disorders
Urinary tract infectionInfections and infestations
Alkaline phosphatase increasedInvestigations
HyponatremiaMetabolism and nutrition disorders
AnxietyPsychiatric disorders
Rash maculo-papularSkin and subcutaneous tissue disorders
HypothyroidismEndocrine disorders
Abdominal distensionGastrointestinal disorders
Abdominal painGastrointestinal disorders
Aspartate aminotransferase increasedInvestigations
Platelet count decreasedInvestigations
MyalgiaMusculoskeletal and connective tissue disorders
DysgeusiaNervous system disorders
DyspneaRespiratory, thoracic and mediastinal disorders
HiccupsRespiratory, thoracic and mediastinal disorders

Most-reported serious reactions: Colitis, Vomiting, Colonic obstruction, Diarrhea, Dysphagia, Nausea, Dehydration, Hyperglycemia.

Data from ClinicalTrials.gov NCT03342937 adverse events section.

Sponsor's own description

This study will be conducted in two stages: 1) safety validation and 2) dose expansion 1. Safety Validation Cohort: The first portion of the study will preliminarily establish the tolerability of the combination of pembrolizumab, oxaliplatin and capecitabine. Five (5) subjects will be enrolled and their safety data after 21 days of treatment will be reviewed before additional subjects are enrolled. Subjects on this portion of the study will only be enrolled at the Duke Cancer Institute. 2. Dose Expansion Cohort: The second portion of the study (ie. phase II) will enroll 30 subjects. In the dose expansion cohort, the first cycle will be modified to allow one week of pembrolizumab monotherapy before starting capecitabine and oxaliplatin (XELOX) chemotherapy, which will allow analysis of biomarkers related to pembrolizumab. Subjects on this portion of the study will be enrolled at the Duke Cancer institute and select external collaborating institutions. The primary objective of this trial is to describe the progression free survival (PFS) associated with the combination of pembrolizumab, oxaliplatin and capecitabine (pembrolizumab +XELOX) in all patients with previously untreated metastatic esophagogastric adenocarcinoma.

Publications & conference data

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

  1. Prognostic significance of tumor immune microenvironment and immunotherapy: Novel insights and future perspectives in gastric cancer.
    Lazăr DC, Avram MF, Romoșan I, Cornianu M, et al · · 2018 · cited 114× · PMID 30166856 · DOI 10.3748/wjg.v24.i32.3583
  2. The role of pembrolizumab in the treatment of PD-L1 expressing gastric and gastroesophageal junction adenocarcinoma.
    Brar G, Shah MA. · · 2019 · cited 31× · PMID 31516556 · DOI 10.1177/1756284819869767
  3. PD-1 Inhibitors in the Advanced Esophageal Cancer.
    Hong Y, Ding ZY. · · 2019 · cited 28× · PMID 31920637 · DOI 10.3389/fphar.2019.01418
  4. Immune checkpoint inhibitor combination therapy for gastric cancer: Research progress.
    Song X, Qi W, Guo J, Sun L, et al · · 2020 · cited 16× · PMID 32802168 · DOI 10.3892/ol.2020.11905
  5. Immunotherapy in Advanced Gastric Cancer: An Overview of the Emerging Strategies.
    Magalhães H, Fontes-Sousa M, Machado M. · · 2018 · cited 13× · PMID 30027089 · DOI 10.1155/2018/2732408
  6. Immune checkpoint inhibitors in gastrointestinal malignancies: what can we learn from experience with other tumors?
    Shah AB, Sommerer KR, Almhanna K. · · 2019 · cited 3× · PMID 31728430 · DOI 10.21037/tgh.2019.09.04
  7. Prognostic and predictive factors in advanced upper gastrointestinal cancer treated with immune checkpoint inhibitors: a systematic review and meta-analysis of the current evidence.
    Wang P, Chen P, Yang W, Yang W, et al · · 2024 · PMID 39385078 · DOI 10.1186/s12885-024-12998-w

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03342937.

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