Last reviewed · How we verify

NCT02718417

Avelumab in Previously Untreated Patients With Epithelial Ovarian Cancer (JAVELIN OVARIAN 100)

Terminated Phase 3 Results posted Last updated 14 July 2020
What this trial tests

Phase 3 trial testing carboplatin in Ovarian Cancer in 998 participants. Terminated before completion.

Timeline
19 May 2016
Primary endpoint
7 September 2018
16 May 2019

Quick facts

Lead sponsorPfizer
PhasePhase 3
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment998
Start date19 May 2016
Primary completion7 September 2018
Estimated completion16 May 2019
Sites319 locations across Hong Kong, Italy, Japan, Taiwan, Ireland, Poland, South Korea, Croatia

Drugs / interventions tested

Conditions studied

Sponsor

Pfizer — full company profile →

Who can join

18 and older, female only, with Ovarian 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.

Progression-Free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR) Primary · Baseline to progression of disease or discontinuation from the study or death, whichever occurred first (maximum duration of 27 months)

BICR assessed PFS: Duration from randomization until disease progression or death. PFS data was censored on the date of the last adequate tumor assessment for participants who did not have an event (progression of disease or death), who started a new anti-cancer therapy prior to an event or for participants with an event after 2 or more missing tumor assessments. Progression as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1: as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the ba

GroupValue95% CI
Chemotherapy Followed by Avelumab16.813.5 – NA
Chemotherapy + Avelumab Followed by Avelumab18.114.8 – NA
Chemotherapy Followed by ObservationNA18.2 – NA
Overall Survival Secondary · Baseline to discontinuation from the study or death, whichever occurred first (maximum duration of 27 months)

Overall survival was defined as the time (in months) from the date of randomization to the date of death due to any cause. Participants last known to be alive were censored at date of last contact. Analysis was performed using Kaplan-Meier method.

GroupValue95% CI
Chemotherapy Followed by AvelumabNANA – NA
Chemotherapy + Avelumab Followed by AvelumabNANA – NA
Chemotherapy Followed by ObservationNANA – NA
Progression-Free Survival (PFS) as Assessed by Investigator Secondary · Baseline to progression of disease or discontinuation from the study or death, whichever occurred first (maximum duration of 27 months)

Investigator assessed PFS was defined as time (in months) from date of randomization to the first documentation of disease progression or death (due to any cause), whichever occurred first. Progression as per RECIST 1.1, was 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 have also demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered pr

GroupValue95% CI
Chemotherapy Followed by Avelumab13.812.1 – 15.9
Chemotherapy + Avelumab Followed by Avelumab16.113.9 – 19.4
Chemotherapy Followed by Observation15.013.2 – 18.7
Percentage of Participants With Objective Response as Assessed by Investigator Secondary · Baseline to progression of disease, start of new anti-cancer therapy or discontinuation from study or death, whichever occurred first (maximum duration of 27 months)

Investigator assessed objective response according to RECIST version 1.1, was defined as participants with confirmed best overall response of complete response (CR) or partial response (PR). CR was defined as disappearance of all target and non-target lesions, and sustained for at least 4 weeks. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 mm. PR was defined as at least 30% decrease in the sum of the longest dimensions of target lesions taking as reference the baseline sum longest dimensions.

GroupValue95% CI
Chemotherapy Followed by Avelumab25.921.3 – 31.0
Chemotherapy + Avelumab Followed by Avelumab31.126.2 – 36.4
Chemotherapy Followed by Observation27.823.0 – 32.9
Percentage of Participants With Objective Response as Assessed by Blinded Independent Central Review (BICR) Secondary · Baseline to progression of disease, start of new anti-cancer therapy or discontinuation from study or death, whichever occurred first (maximum duration of 27 months)

BICR assessed objective response according to RECIST version 1.1, was defined as participants with confirmed best overall response of CR or PR. CR was defined as disappearance of all target and non-target lesions, and sustained for at least 4 weeks. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least 30% decrease in the sum of the longest dimensions of target lesions taking as reference the baseline sum longest dimensions.

GroupValue95% CI
Chemotherapy Followed by Avelumab30.425.5 – 35.7
Chemotherapy + Avelumab Followed by Avelumab36.030.8 – 41.4
Chemotherapy Followed by Observation30.425.6 – 35.7
Duration of Response (DOR) as Assessed by Investigator Secondary · First response subsequently confirmed to progression of disease or start of new anti-cancer therapy or discontinuation from the study or death, whichever occurred first (maximum duration of 27 months)

Investigator assessed DOR: time (in months) from the first documentation of objective response (confirmed CR or PR) to the date of first documentation of PD or death due to any cause. As per RECIST version 1.1, CR was defined as disappearance of all target and non-target lesions, and sustained for at least 4 weeks. Any pathological lymph nodes (target or non-target) must have reduction in short axis to \<10 mm. PR: at least 30% decrease in the sum of the longest dimensions of target lesions taking as reference the baseline sum longest dimensions. PD was defined as at least a 20% increase in th

GroupValue95% CI
Chemotherapy Followed by Avelumab10.68.3 – 20.2
Chemotherapy + Avelumab Followed by AvelumabNA11.7 – NA
Chemotherapy Followed by Observation15.48.3 – 18.4
Duration of Response (DOR) as Assessed by Blinded Independent Central Review (BICR) Secondary · First response subsequently confirmed to progression of disease or start of new anti-cancer therapy or discontinuation from the study or death, whichever occurred first (maximum duration of 27 months)

BICR assessed DOR: time (in months) from the first documentation of objective response (confirmed CR or PR) to the date of first documentation of PD or death due to any cause. As per RECIST version 1.1, CR was defined as disappearance of all target and non-target lesions, and sustained for at least 4 weeks. Any pathological lymph nodes (target or non-target) must have reduction in short axis to \<10 mm. PR: at least 30% decrease in the sum of the longest dimensions of target lesions taking as reference the baseline sum longest dimensions. PD was defined as at least a 20% increase in the sum of

GroupValue95% CI
Chemotherapy Followed by Avelumab11.98.9 – NA
Chemotherapy + Avelumab Followed by Avelumab14.511.7 – NA
Chemotherapy Followed by ObservationNA16.1 – NA
Maintenance Progression-Free Survival as Assessed by Blinded Independent Central Review (BICR) Secondary · From Day 1 of Cycle 1 (42 days) of maintenance phase to progression of disease or death, whichever occurred first (maximum duration of 27 months)

BICR assessed maintenance PFS was defined as the time from Cycle 1 Day 1 of the maintenance phase to the date of the first documentation of PD or death due to any cause, whichever occurs first. It was defined, for participants who proceeded to maintenance phase and who did not have disease progression by BICR during the chemotherapy phase. As per RECIST version 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that is the smallest on study). In addition to the relative incre

GroupValue95% CI
Chemotherapy Followed by Avelumab13.69.3 – NA
Chemotherapy + Avelumab Followed by Avelumab13.811.1 – NA
Chemotherapy Followed by ObservationNA13.8 – NA
Maintenance Progression-Free Survival (PFS) as Assessed by Investigator Secondary · From Day 1 of Cycle 1 (42 days) of maintenance phase to progression of disease or death, whichever occurred first (maximum duration of 27 months)

Investigator assessed maintenance PFS was defined as the time from Cycle 1 Day 1 of the maintenance phase to the date of the first documentation of PD or death due to any cause, whichever occurs first. It was defined, for participants who proceeded to maintenance phase and who did not have disease progression by investigator during the chemotherapy phase. As per RECIST version 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that is the smallest on study). In addition to th

GroupValue95% CI
Chemotherapy Followed by Avelumab10.48.2 – 13.6
Chemotherapy + Avelumab Followed by Avelumab11.69.9 – 13.8
Chemotherapy Followed by Observation12.79.5 – NA
Percentage of Participants With Pathological Complete Response (pCR) Secondary · Baseline to progression of disease or discontinuation from the study or death, whichever occurred first (maximum duration of 27 months)

pCR was defined (for neoadjuvant participants who underwent interval debulking surgery \[IDS\]), as the chemotherapy response score 3 (CSR3), based on a study by Bohm et al, 2015. CSR3 was defined as complete or near-complete response with no residual tumor or minimal irregularly scattered tumor foci seen as individual cells, cell groups, or nodules up to 2 mm. Complete or near-complete response was defined as complete or near-complete microscopic disappearance of invasive tumor/ residual disease.

GroupValue95% CI
Chemotherapy Followed by Avelumab15.7
Chemotherapy + Avelumab Followed by Avelumab17.4
Chemotherapy Followed by Observation25.9
Number of Participants With Treatment-Emergent Adverse Events (AEs) Graded Based on, National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 Secondary · Baseline to discontinuation from the study or death, whichever occurred first (maximum duration of 36 months)

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per NCI-CTCAE version 4.03, Grade 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care

Grade 1
GroupValue95% CI
Chemotherapy Followed by Avelumab11
Chemotherapy + Avelumab Followed by Avelumab13
Chemotherapy Followed by Observation15
Grade 2
GroupValue95% CI
Chemotherapy Followed by Avelumab89
Chemotherapy + Avelumab Followed by Avelumab77
Chemotherapy Followed by Observation96
Grade 3
GroupValue95% CI
Chemotherapy Followed by Avelumab151
Chemotherapy + Avelumab Followed by Avelumab148
Chemotherapy Followed by Observation131
Grade 4
GroupValue95% CI
Chemotherapy Followed by Avelumab67
Chemotherapy + Avelumab Followed by Avelumab84
Chemotherapy Followed by Observation76
Grade 5
GroupValue95% CI
Chemotherapy Followed by Avelumab5
Chemotherapy + Avelumab Followed by Avelumab6
Chemotherapy Followed by Observation3
Number of Participants With Laboratory Abnormalities Greater Than or Equal to (>=) Grade 3, Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 Secondary · Baseline to discontinuation from the study or death, whichever occurred first (maximum duration of 27 months)

As per NCI-CTCAE v 4.03, Grade 3 and above criteria were; Hematology \[Anemia - Grade 3: hemoglobin \<8.0 grams per deciliter (g/dL), \<4.9 millimoles per liter (mmol/L), \<80 grams per liter (g/L), transfusion indicated, Grade 4: life-threatening consequences, urgent intervention indicated, Grade 5: death; platelet count decreased- Grade 3:\<50.0 to 25.0\*10\^9/Liters(L), Grade 4: \<25.0\*10\^9/L; lymphocyte count decreased-Grade 3: \<0.5-0.2\*10\^9/L, Grade 4: \<0.2\*10\^9/L; neutrophil count decreased-Grade 3: \<1.0 to 0.5\*10\^9 /L, Grade 4: \<0.5\*10\^9/L\]. Chemistry \[creatinine increas

Anemia
GroupValue95% CI
Chemotherapy Followed by Avelumab73
Chemotherapy + Avelumab Followed by Avelumab68
Chemotherapy Followed by Observation63
Platelet Count Decreased
GroupValue95% CI
Chemotherapy Followed by Avelumab20
Chemotherapy + Avelumab Followed by Avelumab35
Chemotherapy Followed by Observation38
Lymphocyte Count Decreased
GroupValue95% CI
Chemotherapy Followed by Avelumab35
Chemotherapy + Avelumab Followed by Avelumab63
Chemotherapy Followed by Observation29
Neutrophil Count Decreased
GroupValue95% CI
Chemotherapy Followed by Avelumab144
Chemotherapy + Avelumab Followed by Avelumab159
Chemotherapy Followed by Observation156
Creatinine Increased
GroupValue95% CI
Chemotherapy Followed by Avelumab2
Chemotherapy + Avelumab Followed by Avelumab7
Chemotherapy Followed by Observation0
Serum Amylase Increased
GroupValue95% CI
Chemotherapy Followed by Avelumab5
Chemotherapy + Avelumab Followed by Avelumab9
Chemotherapy Followed by Observation10
Lipase Increased
GroupValue95% CI
Chemotherapy Followed by Avelumab19
Chemotherapy + Avelumab Followed by Avelumab24
Chemotherapy Followed by Observation11
ALT or AST
GroupValue95% CI
Chemotherapy Followed by Avelumab0
Chemotherapy + Avelumab Followed by Avelumab1
Chemotherapy Followed by Observation0

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline up to maximum duration of 36 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Chemotherapy Followed by Avelumab
Serious: 92/328 (28%)
Deaths: 34/328
Chemotherapy + Avelumab Followed by Avelumab
Serious: 118/329 (36%)
Deaths: 31/329
Chemotherapy Followed by Observation
Serious: 64/334 (19%)
Deaths: 20/334

Serious adverse events (189 terms)

ReactionSystemChemotherapy Followed by A…Chemotherapy + Avelumab Fo…Chemotherapy Followed by O…
Febrile neutropeniaBlood and lymphatic system disorders
PyrexiaGeneral disorders
IleusGastrointestinal disorders
AnaemiaBlood and lymphatic system disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
Small intestinal obstructionGastrointestinal disorders
Urinary tract infectionInfections and infestations
VomitingGastrointestinal disorders
Intestinal obstructionGastrointestinal disorders
AscitesGastrointestinal disorders
NauseaGastrointestinal disorders
ThrombocytopeniaBlood and lymphatic system disorders
Abdominal painGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
Infusion related reactionInjury, poisoning and procedural complications
Chest painGeneral disorders
ConstipationGastrointestinal disorders
DehydrationMetabolism and nutrition disorders
Disease progressionGeneral disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
PneumoniaInfections and infestations
Acute kidney injuryRenal and urinary disorders
Device related infectionInfections and infestations
EmbolismVascular disorders
Gastrointestinal obstructionGastrointestinal disorders
Other adverse events (60 terms — click to expand)

ReactionSystemChemotherapy Followed by A…Chemotherapy + Avelumab Fo…Chemotherapy Followed by O…
AlopeciaSkin and subcutaneous tissue disorders
NauseaGastrointestinal disorders
AnaemiaBlood and lymphatic system disorders
NeutropeniaBlood and lymphatic system disorders
FatigueGeneral disorders
ConstipationGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
Peripheral sensory neuropathyNervous system disorders
VomitingGastrointestinal disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Neuropathy peripheralNervous system disorders
Neutrophil count decreasedInvestigations
Abdominal painGastrointestinal disorders
MyalgiaMusculoskeletal and connective tissue disorders
RashSkin and subcutaneous tissue disorders
Decreased appetiteMetabolism and nutrition disorders
ThrombocytopeniaBlood and lymphatic system disorders
CoughRespiratory, thoracic and mediastinal disorders
HeadacheNervous system disorders
InsomniaPsychiatric disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
AstheniaGeneral disorders
Urinary tract infectionInfections and infestations
DizzinessNervous system disorders
Platelet count decreasedInvestigations
HypomagnesaemiaMetabolism and nutrition disorders
PyrexiaGeneral disorders
Abdominal pain upperGastrointestinal disorders
PruritusSkin and subcutaneous tissue disorders
Pain in extremityMusculoskeletal and connective tissue disorders
Back painMusculoskeletal and connective tissue disorders
HypothyroidismEndocrine disorders
White blood cell count decreasedInvestigations
Alanine aminotransferase increasedInvestigations
DyspepsiaGastrointestinal disorders
Infusion related reactionInjury, poisoning and procedural complications
Oedema peripheralGeneral disorders
Aspartate aminotransferase increasedInvestigations
LeukopeniaBlood and lymphatic system disorders
StomatitisGastrointestinal disorders

Most-reported serious reactions: Febrile neutropenia, Pyrexia, Ileus, Anaemia, Pulmonary embolism, Small intestinal obstruction, Urinary tract infection, Vomiting.

Data from ClinicalTrials.gov NCT02718417 adverse events section.

Sponsor's own description

This is a Phase 3, open-label, international, multi-center, efficacy, and safety study of avelumab in combination with and/or following platinum-based chemotherapy. Eligible patients must have previously untreated, histologically confirmed Stage III-IV epithelial ovarian (EOC), fallopian tube cancer (FTC), or primary peritoneal cancer (PPC) and be candidates for platinum-based chemotherapy. The primary purpose of the study is to demonstrate if avelumab given as single agent in the maintenance setting following frontline chemotherapy or in combination with carboplatin/paclitaxel is superior to platinum-based chemotherapy alone followed by observation in this population of newly diagnosed ovarian cancer patients.

Publications & conference data

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

  1. 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
  2. Advances in ovarian cancer therapy.
    Cortez AJ, Tudrej P, Kujawa KA, Lisowska KM. · · 2018 · cited 417× · PMID 29249039 · DOI 10.1007/s00280-017-3501-8
  3. Efficacy and Safety of Avelumab for Patients With Recurrent or Refractory Ovarian Cancer: Phase 1b Results From the JAVELIN Solid Tumor Trial.
    Disis ML, Taylor MH, Kelly K, Beck JT, et al · · 2019 · cited 361× · PMID 30676622 · DOI 10.1001/jamaoncol.2018.6258
  4. Immunotherapy in ovarian cancer.
    Odunsi K. · · 2017 · cited 292× · PMID 29232467 · DOI 10.1093/annonc/mdx444
  5. 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
  6. 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
  7. Chemotherapy with or without avelumab followed by avelumab maintenance versus chemotherapy alone in patients with previously untreated epithelial ovarian cancer (JAVELIN Ovarian 100): an open-label, randomised, phase 3 trial.
    Monk BJ, Colombo N, Oza AM, Fujiwara K, et al · · 2021 · cited 204× · PMID 34363762 · DOI 10.1016/s1470-2045(21)00342-9
  8. Targeted therapies in gynecological cancers: a comprehensive review of clinical evidence.
    Wang Q, Peng H, Qi X, Wu M, et al · · 2020 · cited 114× · PMID 32728057 · DOI 10.1038/s41392-020-0199-6

Verify or expand the search:

Other trials of carboplatin

Trials testing the same drug.

Other recruiting trials for Ovarian Cancer

Currently open trials in the same condition.

Other Pfizer trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

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/NCT02718417.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing