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NCT02625623

Avelumab in Third-Line Gastric Cancer (JAVELIN Gastric 300)

Completed Phase 3 Results posted Last updated 24 November 2020
What this trial tests

Phase 3 trial testing Avelumab in Unresectable, Recurrent, Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma in 371 participants. Completed in 13 November 2019.

Timeline
28 December 2015
Primary endpoint
14 September 2017
13 November 2019

Quick facts

Lead sponsorEMD Serono Research & Development Institute, Inc.
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment371
Start date28 December 2015
Primary completion14 September 2017
Estimated completion13 November 2019
Sites75 locations across France, Italy, Belgium, Germany, Poland, South Korea, Australia, United States

Drugs / interventions tested

Conditions studied

Sponsor

EMD Serono Research & Development Institute, Inc. — full company profile →

Who can join

18 and older, any sex, with Unresectable, Recurrent, Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma or Gastric Cancer Third Line. 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.

Overall Survival (OS) Primary · From randomization up to 627 days

OS was defined as the time from randomization to the date of death due to any cause. For participants who were still alive at the time of data analysis or who were lost to follow-up, OS time was censored at the date of last contact. OS was measured using Kaplan-Meier (KM) estimates.

GroupValue95% CI
Physician Choice Chemotherapy + Best Supportive Care (BSC)5.04.5 – 6.3
Avelumab + BSC4.63.6 – 5.7
Progression Free Survival (PFS) Secondary · From randomization up to 627 days

The PFS time was defined as the time from date of randomization until date of the first documentation of progressive disease (PD) or death due to any cause (whichever occurs first). PFS was assessed as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). PD was defined as at least a 20 percent (%) increase in the sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. PFS was measured using Kaplan-Meier (KM) estimates.

GroupValue95% CI
Physician Choice Chemotherapy + Best Supportive Care (BSC)2.71.81 – 2.83
Avelumab + BSC1.41.38 – 1.45
Best Overall Response (BOR) Secondary · From randomization up to 627 days

BOR was determined by RECIST v1.1 and defined as best-confirmed response of any of following: complete response (CR), partial response (PR), stable disease (SD) and PD recorded from date of randomization until disease progression or recurrence. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in SLD of all lesions. SD: Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD is defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or appearance of

GroupValue95% CI
Physician Choice Chemotherapy + Best Supportive Care (BSC)1
Avelumab + BSC1
Physician Choice Chemotherapy + Best Supportive Care (BSC)7
Avelumab + BSC3
Physician Choice Chemotherapy + Best Supportive Care (BSC)62
Avelumab + BSC30
Physician Choice Chemotherapy + Best Supportive Care (BSC)12
Avelumab + BSC7
Objective Response Rate (ORR) Secondary · From randomization up to 627 days

The ORR defined as the percentage of all randomized participants with a confirmed best overall response (BOR) of partial response (PR),or complete response (CR) according to RECIST v1.1 and as adjudicated by the Independent Review Committee (IRC). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in sum of longest diameter (SLD) of all lesions.

GroupValue95% CI
Physician Choice Chemotherapy + Best Supportive Care (BSC)4.31.9 – 8.3
Avelumab + SC2.20.6 – 5.4
Change From Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire Through Composite Index Score at End of Treatment (EOT) Secondary · Baseline, EOT (up to Week 66)

EQ-5D-5L is comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive overall composite health state index score, with scores ranging from -0.594 to 1. A higher score indicates better health state.

GroupValue95% CI
Physician Choice Chemotherapy + Best Supportive Care (BSC)-0.103± 0.2113
Avelumab + BSC-0.144± 0.2088
Change From Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire Through Visual Analogue Scale (VAS) at End of Treatment (EOT) Secondary · Baseline, EOT (up to Week 66)

EQ-5D-5L is comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive overall score using a visual analog scale (VAS) that ranged from 0 to 100 millimeter (mm), where 0 is the worst health you can imagine and 100 is the best health you can imagine.

GroupValue95% CI
Physician Choice Chemotherapy + Best Supportive Care (BSC)-12.3± 19.22
Avelumab + BSC-13.6± 19.76
Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) Global Health Status Scale Score at End of Treatment (EOT) Secondary · Baseline, EOT (up to Week 66)

EORTC QLQ-C30 is a 30-question tool used to assess the overall quality of life (QoL) in cancer participants. It consisted of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, role, cognitive, emotional, social), and 9 symptom scales/items (Fatigue, nausea and vomiting, pain, dyspnoea, sleep disturbance, appetite loss, constipation, diarrhea, financial impact. The EORTC QLQ-C30 GHS/QoL score ranges from 0 to 100; High score indicates better GHS/QoL. Score 0 represents: very poor physical condition and QoL. Score 100 represents: excellent overall physical condition a

GroupValue95% CI
Physician Choice Chemotherapy + Best Supportive Care (BSC)-10.14± 19.914
Avelumab + BSC-15.77± 19.437
Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Stomach Cancer Specific (EORTC QLQ-STO22) Questionnaire Scores at End of Treatment (EOT) Secondary · Baseline, EOT (up to Week 66)

The EORTC QLQ-STO22 supplements the EORTC QLQ-C30 to assess symptoms and treatment-related side effects commonly reported in participants. There are 22 questions which comprise 5 scales (dysphagia, pain, reflux symptom, dietary restrictions, and anxiety) and 4 single items (dry mouth, hair loss, taste, body image). Most questions use 4-point scale (1 'Not at all' to 4 'Very much'; 1 question was a yes or no answer). A linear transformation was used to standardize all scores and single-items to a scale of 0 to 100; higher score=better level of functioning or greater degree of symptoms.

Dysphagia
GroupValue95% CI
Physician Choice Chemotherapy + Best Supportive Care (BSC)7.25± 28.551
Avelumab + BSC15.32± 29.120
Pain
GroupValue95% CI
Physician Choice Chemotherapy + Best Supportive Care (BSC)8.88± 22.402
Avelumab + BSC9.23± 21.527
Reflux
GroupValue95% CI
Physician Choice Chemotherapy + Best Supportive Care (BSC)4.59± 20.184
Avelumab + BSC7.96± 18.347
Eating Restrictions
GroupValue95% CI
Physician Choice Chemotherapy + Best Supportive Care (BSC)9.24± 22.661
Avelumab + BSC13.29± 21.276
Anxiety
GroupValue95% CI
Physician Choice Chemotherapy + Best Supportive Care (BSC)7.49± 21.860
Avelumab + BSC6.61± 19.456
Dry Mouth
GroupValue95% CI
Physician Choice Chemotherapy + Best Supportive Care (BSC)15.94± 27.725
Avelumab + BSC9.01± 28.827
Tasting
GroupValue95% CI
Physician Choice Chemotherapy + Best Supportive Care (BSC)9.42± 25.832
Avelumab + BSC2.25± 35.897
Body Image
GroupValue95% CI
Physician Choice Chemotherapy + Best Supportive Care (BSC)5.07± 28.787
Avelumab + BSC4.05± 27.561

Adverse events — posted to ClinicalTrials.gov

Time frame: From randomization up to 627 days. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Physician Choice Chemotherapy + Best Supportive Care (BSC)
Serious: 81/177 (46%)
Deaths: 131/177
Avelumab + BSC
Serious: 90/184 (49%)
Deaths: 142/184

Serious adverse events (102 terms)

ReactionSystemPhysician Choice Chemother…Avelumab + BSC
Disease progressionGeneral disorders
General physical health deteriorationGeneral disorders
Abdominal painGastrointestinal disorders
VomitingGastrointestinal disorders
PneumoniaInfections and infestations
AnaemiaBlood and lymphatic system disorders
Intestinal obstructionGastrointestinal disorders
IleusGastrointestinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Decreased appetiteMetabolism and nutrition disorders
AstheniaGeneral disorders
AscitesGastrointestinal disorders
DysphagiaGastrointestinal disorders
SubileusGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
SepsisInfections and infestations
Febrile neutropeniaBlood and lymphatic system disorders
DehydrationMetabolism and nutrition disorders
Oedema peripheralGeneral disorders
Abdominal pain upperGastrointestinal disorders
NauseaGastrointestinal disorders
Device related infectionInfections and infestations
Herpes zosterInfections and infestations
Tumour painNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatic failureHepatobiliary disorders
Other adverse events (29 terms — click to expand)

ReactionSystemPhysician Choice Chemother…Avelumab + BSC
NauseaGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
AnaemiaBlood and lymphatic system disorders
Decreased appetiteMetabolism and nutrition disorders
AstheniaGeneral disorders
VomitingGastrointestinal disorders
Abdominal painGastrointestinal disorders
PyrexiaGeneral disorders
FatigueGeneral disorders
ConstipationGastrointestinal disorders
NeutropeniaBlood and lymphatic system disorders
AlopeciaSkin and subcutaneous tissue disorders
ChillsGeneral disorders
Abdominal pain upperGastrointestinal disorders
Infusion related reactionInjury, poisoning and procedural complications
Back painMusculoskeletal and connective tissue disorders
Oedema peripheralGeneral disorders
Aspartate aminotransferase increasedInvestigations
Weight decreasedInvestigations
Neutrophil count decreasedInvestigations
Gamma-glutamyltransferase increasedInvestigations
DyspnoeaRespiratory, thoracic and mediastinal disorders
Blood alkaline phosphatase increasedInvestigations
White blood cell count decreasedInvestigations
Peripheral sensory neuropathyNervous system disorders
Alanine aminotransferase increasedInvestigations
DysphagiaGastrointestinal disorders
DehydrationMetabolism and nutrition disorders
CoughRespiratory, thoracic and mediastinal disorders

Most-reported serious reactions: Disease progression, General physical health deterioration, Abdominal pain, Vomiting, Pneumonia, Anaemia, Intestinal obstruction, Ileus.

Data from ClinicalTrials.gov NCT02625623 adverse events section.

Sponsor's own description

The purpose of this study was to demonstrate superiority of treatment with avelumab plus best supportive care (BSC) versus physician's choice (chosen from a pre-specified list of therapeutic options) plus BSC.

Publications & conference data

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

  1. Immune checkpoint inhibitors: recent progress and potential biomarkers.
    Darvin P, Toor SM, Sasidharan Nair V, Elkord E. · · 2018 · cited 1495× · PMID 30546008 · DOI 10.1038/s12276-018-0191-1
  2. PD-1 and PD-L1 Checkpoint Signaling Inhibition for Cancer Immunotherapy: Mechanism, Combinations, and Clinical Outcome.
    Alsaab HO, Sau S, Alzhrani R, Tatiparti K, et al · · 2017 · cited 1206× · PMID 28878676 · DOI 10.3389/fphar.2017.00561
  3. Phase III, randomised trial of avelumab versus physician's choice of chemotherapy as third-line treatment of patients with advanced gastric or gastro-oesophageal junction cancer: primary analysis of JAVELIN Gastric 300.
    Bang YJ, Ruiz EY, Van Cutsem E, Lee KW, et al · · 2018 · cited 388× · PMID 30052729 · DOI 10.1093/annonc/mdy264
  4. Avelumab for metastatic or locally advanced previously treated solid tumours (JAVELIN Solid Tumor): a phase 1a, multicohort, dose-escalation trial.
    Heery CR, O'Sullivan-Coyne G, Madan RA, Cordes L, et al · · 2017 · cited 228× · PMID 28373007 · DOI 10.1016/s1470-2045(17)30239-5
  5. Genetic, transcriptional and post-translational regulation of the programmed death protein ligand 1 in cancer: biology and clinical correlations.
    Zerdes I, Matikas A, Bergh J, Rassidakis GZ, et al · · 2018 · cited 223× · PMID 29765155 · DOI 10.1038/s41388-018-0303-3
  6. Antibodies to watch in 2018.
    Kaplon H, Reichert JM. · · 2018 · cited 179× · PMID 29300693 · DOI 10.1080/19420862.2018.1415671
  7. Outlooks on Epstein-Barr virus associated gastric cancer.
    Naseem M, Barzi A, Brezden-Masley C, Puccini A, et al · · 2018 · cited 156× · PMID 29631196 · DOI 10.1016/j.ctrv.2018.03.006
  8. The Use of Immune Checkpoint Inhibitors in Oncology and the Occurrence of AKI: Where Do We Stand?
    Franzin R, Netti GS, Spadaccino F, Porta C, et al · · 2020 · cited 142× · PMID 33162990 · DOI 10.3389/fimmu.2020.574271

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