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NCT02493751

A Study Of Avelumab In Combination With Axitinib In Advanced Renal Cell Cancer (JAVELIN Renal 100)

Completed Phase 1 Results posted Last updated 18 February 2022
What this trial tests

Phase 1 trial testing Avelumab (MSB0010718C) in Renal Cell Cancer in 55 participants. Completed in 4 March 2021.

Timeline
26 October 2015
Primary endpoint
3 April 2018
4 March 2021

Quick facts

Lead sponsorPfizer
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Maskingnone
Primary purposetreatment
Enrollment55
Start date26 October 2015
Primary completion3 April 2018
Estimated completion4 March 2021
Sites21 locations across United Kingdom, Japan, United States

Drugs / interventions tested

Conditions studied

Sponsor

Pfizer — full company profile →

Who can join

18 and older, any sex, with Renal Cell 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.

Number of Participants With Dose Limiting Toxicities (DLTs) Primary · DLT observation period (from the beginning of Cycle 1 up to the end of Cycle 2 [28 days])

DLT: greater than or equal to (\>=) Grade 3 hematologic/non-hematologic toxicity, Grade 3-4 liver-related laboratory test elevation (alanine aminotransferase, aspartate aminotransferase) with Grade 2 elevation of total bilirubin, non-hematologic Grade 3 laboratory abnormality (required medical intervention to treat participant/led to hospitalization), inability to complete \>=75% of first 2 cycles doses of axitinib (from Cycle 1 Day 1 after completion of lead-in period) or 2 infusions of avelumab within DLT observation period due to investigational product related toxicity.

GroupValue95% CI
Axitinib + Avelumab With Lead-in1
Number of Participants With All-causality Treatment Emergent Adverse Events (TEAEs) Secondary · Baseline up to 30 days after the last dose of study treatment (maximum of 259.7 weeks)

Adverse event (AE)=any untoward medical occurrence in participant who received study treatment without regard to causality. TEAE=event between first dose of study treatment and up to 30 days after last dose that were absent before treatment or worsened relative to pretreatment state. Serious AE (SAE)=AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience; persistent or significant disability/incapacity; congenital anomaly. AEs were graded by worst National Cancer Institute (NCI

Participants with TEAEs
GroupValue95% CI
Axitinib + Avelumab With Lead-in16
Axitinib + Avelumab39
Participants with Grade >=3 TEAEs
GroupValue95% CI
Axitinib + Avelumab With Lead-in13
Axitinib + Avelumab30
Participants with SAEs
GroupValue95% CI
Axitinib + Avelumab With Lead-in6
Axitinib + Avelumab18
Number of Participants With Treatment-related TEAEs Secondary · Baseline up to 30 days after the last dose of study treatment (maximum of 259.7 weeks)

Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. TEAE=event between first dose of study treatment and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience; persistent or significant disability/incapacity; congenital anomaly. AEs were graded by worst NCI CTCAE v4.03 severity gra

Participants with treatment-related TEAEs
GroupValue95% CI
Axitinib + Avelumab With Lead-in15
Axitinib + Avelumab39
Participants with Grade >=3 treatment-related TEAEs
GroupValue95% CI
Axitinib + Avelumab With Lead-in11
Axitinib + Avelumab23
Participants with treatment-related SAEs
GroupValue95% CI
Axitinib + Avelumab With Lead-in3
Axitinib + Avelumab10
Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Hematology Secondary · Baseline up to 30 days after the last dose of study treatment and 1 day before the start day of new anti-cancer drug therapy (maximum of 259.7 weeks)

Laboratory abnormalities (hematology) reported included anemia, platelet count decreased, lymphocyte count decreased, and neutrophil count decreased. Grade 1=mild transient reaction; infusion interruption not indicated; intervention not indicated. Grade 2=therapy or infusion interruption indicated but responds promptly to symptomatic treatment; prophylactic medications indicated for \<=24 hours. Grade 3=prolonged; recurrence of symptoms following initial improvement; hospitalization indicated for clinical sequelae. Grade 4=life threatening consequences; urgent intervention indicated. Grade 5=d

Participants with Grade >=1 anemia
GroupValue95% CI
Axitinib + Avelumab With Lead-in8
Axitinib + Avelumab24
Participants with Grade >=3 anemia
GroupValue95% CI
Axitinib + Avelumab With Lead-in0
Axitinib + Avelumab2
Participants with Grade >=1 platelet count decreased
GroupValue95% CI
Axitinib + Avelumab With Lead-in4
Axitinib + Avelumab11
Participants with Grade >=3 platelet count decreased
GroupValue95% CI
Axitinib + Avelumab With Lead-in0
Axitinib + Avelumab0
Participants with Grade >=1 lymphocyte count decreased
GroupValue95% CI
Axitinib + Avelumab With Lead-in10
Axitinib + Avelumab16
Participants with Grade >=3 lymphocyte count decreased
GroupValue95% CI
Axitinib + Avelumab With Lead-in1
Axitinib + Avelumab3
Participants with Grade >=1 neutrophil count decreased
GroupValue95% CI
Axitinib + Avelumab With Lead-in1
Axitinib + Avelumab4
Participants with Grade >=3 neutrophil count decreased
GroupValue95% CI
Axitinib + Avelumab With Lead-in0
Axitinib + Avelumab0
Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry Secondary · Baseline up to 30 days after the last dose of study treatment and 1 day before the start day of new anti-cancer drug therapy (maximum of 259.7 weeks)

Laboratory abnormalities (chemistry) reported included creatinine increased, serum amylase increased, lipase increased, alanine aminotransferase (ALT) increased, aspartate aminotransferase (AST) increased, blood bilirubin increased, creatine kinase increased, hypoglycemia, and hyperglycemia. Grade 1=mild transient reaction; infusion interruption not indicated; intervention not indicated. Grade 2=therapy or infusion interruption indicated but responds promptly to symptomatic treatment; prophylactic medications indicated for \<=24 hours. Grade 3=prolonged; recurrence of symptoms following initia

Participants with Grade >=1 creatinine increased
GroupValue95% CI
Axitinib + Avelumab With Lead-in16
Axitinib + Avelumab37
Participants with Grade >=3 creatinine increased
GroupValue95% CI
Axitinib + Avelumab With Lead-in0
Axitinib + Avelumab0
Participants with Grade >=1 serum amylase increased
GroupValue95% CI
Axitinib + Avelumab With Lead-in11
Axitinib + Avelumab16
Participants with Grade >=3 serum amylase increased
GroupValue95% CI
Axitinib + Avelumab With Lead-in4
Axitinib + Avelumab3
Participants with Grade >=1 lipase increased
GroupValue95% CI
Axitinib + Avelumab With Lead-in9
Axitinib + Avelumab16
Participants with Grade >=3 lipase increased
GroupValue95% CI
Axitinib + Avelumab With Lead-in5
Axitinib + Avelumab8
Participants with Grade >=1 ALT increased
GroupValue95% CI
Axitinib + Avelumab With Lead-in8
Axitinib + Avelumab20
Participants with Grade >=3 ALT increased
GroupValue95% CI
Axitinib + Avelumab With Lead-in2
Axitinib + Avelumab2
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure Secondary · Baseline, Day 1 of each cycle, Day 8 of Cycles 1 and 2, end of treatment, Follow-up Days 30, 60, 90 for all participants in the analysis population, and Lead-in Day 7 for participants with lead-in (maximum of 139.6 weeks by PCD)

Blood pressure was taken with the participant in the seated position after the participant had been sitting quietly for at least 5 minutes. Baseline was defined as the last assessment prior to the date/time of the first dose of study treatment, which occurred on Day 1 in Lead-in period for participants with lead-in, and occurred on Cycle 1 Day 1 (C1D1) for participants without lead-in. The results reflect data available on cutoff of primary completion date (PCD) (03 Apr 2018).

Lead-in Day 7
GroupValue95% CI
Axitinib + Avelumab With Lead-in5.4± 9.32
C1D1
GroupValue95% CI
Axitinib + Avelumab With Lead-in4.1± 9.36
C1D8
GroupValue95% CI
Axitinib + Avelumab With Lead-in3.2± 12.80
Axitinib + Avelumab9.8± 11.81
C2D1
GroupValue95% CI
Axitinib + Avelumab With Lead-in3.4± 13.15
Axitinib + Avelumab10.1± 10.03
C2D8
GroupValue95% CI
Axitinib + Avelumab With Lead-in1.8± 10.01
Axitinib + Avelumab14.7± 5.03
C3D1
GroupValue95% CI
Axitinib + Avelumab With Lead-in6.1± 12.16
Axitinib + Avelumab10.2± 11.80
C4D1
GroupValue95% CI
Axitinib + Avelumab With Lead-in3.6± 10.34
Axitinib + Avelumab8.8± 9.60
C5D1
GroupValue95% CI
Axitinib + Avelumab With Lead-in4.8± 10.53
Axitinib + Avelumab6.9± 11.64
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure Secondary · Baseline, Day 1 of each cycle, Day 8 of Cycles 1 and 2, end of treatment, Follow-up Days 30, 60, 90 for all participants in the analysis population, and Lead-in Day 7 for participants with lead-in (maximum of 139.6 weeks by PCD)

Blood pressure was taken with the participant in the seated position after the participant had been sitting quietly for at least 5 minutes. Baseline was defined as the last assessment prior to the date/time of the first dose of study treatment, which occurred on Day 1 in Lead-in period for participants with lead-in, and occurred on Cycle 1 Day 1 (C1D1) for participants without lead-in. The results reflect data available on cutoff of PCD (03 Apr 2018).

Lead-in Day 7
GroupValue95% CI
Axitinib + Avelumab With Lead-in9.7± 13.44
C1D1
GroupValue95% CI
Axitinib + Avelumab With Lead-in11.0± 18.20
C1D8
GroupValue95% CI
Axitinib + Avelumab With Lead-in8.0± 18.94
Axitinib + Avelumab10.3± 16.12
C2D1
GroupValue95% CI
Axitinib + Avelumab With Lead-in4.6± 18.49
Axitinib + Avelumab11.2± 11.47
C2D8
GroupValue95% CI
Axitinib + Avelumab With Lead-in0.8± 15.63
Axitinib + Avelumab17.7± 6.66
C3D1
GroupValue95% CI
Axitinib + Avelumab With Lead-in9.9± 18.96
Axitinib + Avelumab8.7± 15.05
C4D1
GroupValue95% CI
Axitinib + Avelumab With Lead-in6.7± 15.61
Axitinib + Avelumab5.8± 11.73
C5D1
GroupValue95% CI
Axitinib + Avelumab With Lead-in6.2± 19.45
Axitinib + Avelumab6.7± 14.90
Change From Baseline in Vital Signs - Pulse Rate Secondary · Baseline, Day 1 of each cycle, Day 8 of Cycles 1 and 2, end of treatment, Follow-up Days 30, 60, 90 for all participants in the analysis population, and Lead-in Day 7 for participants with lead-in (maximum of 139.6 weeks by PCD)

Pulse rate was taken with the participant in the seated position after the participant had been sitting quietly for at least 5 minutes. Baseline was defined as the last assessment prior to the date/time of the first dose of study treatment, which occurred on Day 1 in Lead-in period for participants with lead-in, and occurred on Cycle 1 Day 1 (C1D1) for participants without lead-in. The results reflect data available on cutoff of PCD (03 Apr 2018).

Lean-in Day 7
GroupValue95% CI
Axitinib + Avelumab With Lead-in-0.5-16.0 – 28.0
C1D1
GroupValue95% CI
Axitinib + Avelumab With Lead-in-1.0-21.0 – 19.0
C1D8
GroupValue95% CI
Axitinib + Avelumab With Lead-in-2.0-20.0 – 24.0
Axitinib + Avelumab-2.0-27.0 – 41.0
C2D1
GroupValue95% CI
Axitinib + Avelumab With Lead-in3.0-20.0 – 24.0
Axitinib + Avelumab4.0-30.0 – 29.0
C2D8
GroupValue95% CI
Axitinib + Avelumab With Lead-in8.0-6.0 – 25.0
Axitinib + Avelumab2.0-14.0 – 10.0
C3D1
GroupValue95% CI
Axitinib + Avelumab With Lead-in4.0-25.0 – 29.0
Axitinib + Avelumab2.0-34.0 – 35.0
C4D1
GroupValue95% CI
Axitinib + Avelumab With Lead-in1.5-20.0 – 24.0
Axitinib + Avelumab4.0-28.0 – 48.0
C5D1
GroupValue95% CI
Axitinib + Avelumab With Lead-in0.0-27.0 – 16.0
Axitinib + Avelumab2.5-40.0 – 26.0
Number of Participants Achieving Objective Response (OR) Based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Secondary · Cycle 1 Day 1 up to 30 months after the first dose

Confirmed OR was defined as complete response (CR) or partial response (PR) according to RECIST v1.1 from the start date until disease progression or death due to any cause. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis \<10 mm). PR was defined as \>= 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. All target lesio

CR
GroupValue95% CI
Axitinib + Avelumab With Lead-in2
Axitinib + Avelumab2
PR
GroupValue95% CI
Axitinib + Avelumab With Lead-in8
Axitinib + Avelumab21
Number of Participants Achieving Disease Control (DC) Based on RECIST Version 1.1 Secondary · Cycle 1 Day 1 up to 30 months after the first dose

DC was defined as OR (CR or PR) or stable disease (SD) per RECIST v1.1 from the start date until the first documentation of objective disease progression or death due to any cause. SD was defined as not qualifying for CR, PR, or progression (PD). PD was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 mm. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must de

GroupValue95% CI
Axitinib + Avelumab With Lead-in15
Axitinib + Avelumab28
Duration of Response (DR) Based on RECIST Version 1.1 Secondary · Cycle 1 Day 1 up to 30 months after the first dose

DR was defined as the time from the first documentation of objective tumor response (CR or PR) that was subsequently confirmed to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis \<10 mm). PR was defined as \>= 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter

GroupValue95% CI
Axitinib + Avelumab With Lead-inNA4.2 – NA
Axitinib + AvelumabNA9.6 – NA
Progression-free Survival (PFS) Secondary · Cycle 1 Day 1 up to 30 months after the first dose

PFS was defined as defined as the time from the start date to the date of the first documentation of objective progression of disease (PD) or death due to any cause, whichever occurred first. PD was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 mm. All target lesions must have been assessed. The results reflect data available on cutoff of PCD (03 Apr 2018).

GroupValue95% CI
Axitinib + Avelumab With Lead-in19.24.4 – NA
Axitinib + Avelumab7.64.1 – NA

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline up to 30 days after last dose of study treatment (maximum duration of 259.7 weeks for participants with Lead-in, and maximum duration of 244.4 weeks for participants without lead-in). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Axitinib + Avelumab With Lead-in
Serious: 6/16 (38%)
Deaths: 6/16
Axitinib + Avelumab
Serious: 18/39 (46%)
Deaths: 14/39

Serious adverse events (38 terms)

ReactionSystemAxitinib + Avelumab With L…Axitinib + Avelumab
Disease progressionGeneral disorders
Infusion related reactionInjury, poisoning and procedural complications
PresyncopeNervous system disorders
Spinal cord compressionNervous system disorders
HaematomaVascular disorders
AnaemiaBlood and lymphatic system disorders
NeutropeniaBlood and lymphatic system disorders
MyocarditisCardiac disorders
PalpitationsCardiac disorders
TachycardiaCardiac disorders
Adrenal insufficiencyEndocrine disorders
DiarrhoeaGastrointestinal disorders
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
Adverse drug reactionGeneral disorders
PyrexiaGeneral disorders
SepsisInfections and infestations
Tooth abscessInfections and infestations
Lower limb fractureInjury, poisoning and procedural complications
Rib fractureInjury, poisoning and procedural complications
Spinal fractureInjury, poisoning and procedural complications
Alanine aminotransferase increasedInvestigations
Amylase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
Lipase increasedInvestigations
Other adverse events (202 terms — click to expand)

ReactionSystemAxitinib + Avelumab With L…Axitinib + Avelumab
DiarrhoeaGastrointestinal disorders
FatigueGeneral disorders
DysphoniaRespiratory, thoracic and mediastinal disorders
HypertensionVascular disorders
RashSkin and subcutaneous tissue disorders
Aspartate aminotransferase increasedInvestigations
ConstipationGastrointestinal disorders
Alanine aminotransferase increasedInvestigations
ArthralgiaMusculoskeletal and connective tissue disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Palmar-plantar erythrodysaesthesia syndromeSkin and subcutaneous tissue disorders
HypothyroidismEndocrine disorders
Mucosal inflammationGeneral disorders
VomitingGastrointestinal disorders
Amylase increasedInvestigations
Decreased appetiteMetabolism and nutrition disorders
CoughRespiratory, thoracic and mediastinal disorders
PruritusSkin and subcutaneous tissue disorders
Weight decreasedInvestigations
NauseaGastrointestinal disorders
Infusion related reactionInjury, poisoning and procedural complications
HypophosphataemiaMetabolism and nutrition disorders
MyalgiaMusculoskeletal and connective tissue disorders
HeadacheNervous system disorders
ChillsGeneral disorders
Upper respiratory tract infectionInfections and infestations
Lipase increasedInvestigations
Muscle spasmsMusculoskeletal and connective tissue disorders
Abdominal painGastrointestinal disorders
Oedema peripheralGeneral disorders
Blood alkaline phosphatase increasedInvestigations
HyperuricaemiaMetabolism and nutrition disorders
DysgeusiaNervous system disorders
InsomniaPsychiatric disorders
ProteinuriaRenal and urinary disorders
Skin ulcerSkin and subcutaneous tissue disorders
AnaemiaBlood and lymphatic system disorders
Dry mouthGastrointestinal disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders
PyrexiaGeneral disorders

Most-reported serious reactions: Disease progression, Infusion related reaction, Presyncope, Spinal cord compression, Haematoma, Anaemia, Neutropenia, Myocarditis.

Data from ClinicalTrials.gov NCT02493751 adverse events section.

Sponsor's own description

This is a Phase 1b, open-label, multi-center, multiple-dose trial designed to estimate the maximum tolerated dose (MTD) and select the recommended phase 2 dose (RP2D) of avelumab (MSB0010718C) in combination with axitinib (AG-013736). Once the MTD of avelumab administered in combination with axitinib is estimated (dose finding portion), the dose expansion phase will be opened to further characterize the combination in term of safety profile, anti tumor activity, pharmacokinetics, pharmacodynamics and biomarker modulation.

Publications & conference data

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

  1. Synergistic effect of immune checkpoint blockade and anti-angiogenesis in cancer treatment.
    Yi M, Jiao D, Qin S, Chu Q, et al · · 2019 · cited 487× · PMID 30925919 · DOI 10.1186/s12943-019-0974-6
  2. Resistance to Systemic Therapies in Clear Cell Renal Cell Carcinoma: Mechanisms and Management Strategies.
    Makhov P, Joshi S, Ghatalia P, Kutikov A, et al · · 2018 · cited 396× · PMID 29967214 · DOI 10.1158/1535-7163.mct-17-1299
  3. Avelumab plus axitinib versus sunitinib in advanced renal cell carcinoma: biomarker analysis of the phase 3 JAVELIN Renal 101 trial.
    Motzer RJ, Robbins PB, Powles T, Albiges L, et al · · 2020 · cited 383× · PMID 32895571 · DOI 10.1038/s41591-020-1044-8
  4. Improvement of the anticancer efficacy of PD-1/PD-L1 blockade via combination therapy and PD-L1 regulation.
    Wu M, Huang Q, Xie Y, Wu X, et al · · 2022 · cited 336× · PMID 35279217 · DOI 10.1186/s13045-022-01242-2
  5. Preliminary results for avelumab plus axitinib as first-line therapy in patients with advanced clear-cell renal-cell carcinoma (JAVELIN Renal 100): an open-label, dose-finding and dose-expansion, phase 1b trial.
    Choueiri TK, Larkin J, Oya M, Thistlethwaite F, et al · · 2018 · cited 208× · PMID 29530667 · DOI 10.1016/s1470-2045(18)30107-4
  6. Anti-angiogenic Agents in Combination With Immune Checkpoint Inhibitors: A Promising Strategy for Cancer Treatment.
    Song Y, Fu Y, Xie Q, Zhu B, et al · · 2020 · cited 198× · PMID 32983126 · DOI 10.3389/fimmu.2020.01956
  7. The society for immunotherapy of cancer consensus statement on immunotherapy for the treatment of advanced renal cell carcinoma (RCC).
    Rini BI, Battle D, Figlin RA, George DJ, et al · · 2019 · cited 197× · PMID 31856918 · DOI 10.1186/s40425-019-0813-8
  8. Immunotherapy in Renal Cell Carcinoma: The Future Is Now.
    Deleuze A, Saout J, Dugay F, Peyronnet B, et al · · 2020 · cited 178× · PMID 32260578 · DOI 10.3390/ijms21072532

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