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NCT04150562

Avelumab (Bavencio) With IL-15 in Subjects With Clear-Cell Renal Carcinoma

Terminated Phase 2 Results posted Last updated 17 May 2022
What this trial tests

Phase 2 trial testing rhIL-15 in Clear-Cell Renal Carcinoma in 2 participants. Terminated before completion.

Timeline
26 May 2020
Primary endpoint
23 July 2021
16 September 2021

Quick facts

Lead sponsorNational Cancer Institute (NCI)
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationnon randomized
Designsequential
Maskingnone
Primary purposetreatment
Enrollment2
Start date26 May 2020
Primary completion23 July 2021
Estimated completion16 September 2021
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

National Cancer Institute (NCI)

Who can join

18 and older, any sex, with Clear-Cell Renal 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.

Overall Response Rate (Complete Response + Partial Response) Primary · Following start of study medication while on treatment, approximately 2 months.

Response was assessed using the Immune Related Response Evaluation Criteria in Solid Tumors (irRECIST)v1.1. Immune related complete response (irCR) is at least two radiographic determinations of complete response (CR - e.g., disappearance of all target lesions) at least 4 weeks apart and before Immune related progressive disease (irPD - defined as at least two consecutive radiographic determinations of progressive disease ((PD - e.g., appearance of one or more new lesions) at least 4 weeks apart). at least 4 weeks apart). Immune related partial response (irPR) is at least two radiographic dete

Immune related complete response (irCR)
GroupValue95% CI
Arm 1- Safety Run-in Dose Level 10
Immune related partial response (irPR)
GroupValue95% CI
Arm 1- Safety Run-in Dose Level 10
Duration of Response Secondary · Following start of study medication while on treatment, up to 1-2 months.

Duration of response is defined as the time from the initial response (irCR, irPR or irSD) to progression or death, whichever comes first. Response was assessed using the Immune Related Response Evaluation Criteria in Solid Tumors (irRECIST)v1.1. Immune related complete response (irCR) is at least two radiographic determinations of complete response (CR) at least 4 weeks apart and before Immune related progressive disease (irPD - defined as at least two consecutive radiographic determinations of progressive disease (PD) at least 4 weeks apart). Immune related partial response (irPR) is at leas

GroupValue95% CI
Arm 1- Safety Run-in Dose Level 1130 – 26
Progression-free Survival Secondary · Monitoring frequency is every two cycles through completion of study then annually until progressive disease is noted, an average of 73 days.

Progression free survival is defined as the duration of time from the date of study enrollment until time of disease relapse, disease progression, or death, whichever comes first. Progression was assessed using the Immune Related Response Evaluation Criteria in Solid Tumors (irRECIST)v1.1. Immune related progressive disease (irPD) is defined as at least two consecutive radiographic determinations of progressive disease (PD - e.g., appearance of one or more new lesions) at least 4 weeks apart).

GroupValue95% CI
Arm 1- Safety Run-in Dose Level 17362 – 84
Overall Survival Secondary · time from the date of study enrollment until time of death from any cause, an average of 167 days

Overall survival is defined as the time from the date of study enrollment until time of death from any cause.

GroupValue95% CI
Arm 1- Safety Run-in Dose Level 1167147 – 187
Number of Grade 3 Adverse Events Possibly, Probably or Definitely Related to Treatment of rhIL-15 + Avelumab Secondary · 4 cycles (each cycle is 28 days), up to 112 days

Adverse events were assessed using the Common Terminology Criteria for Adverse Events (CTCAE)v5.0. Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse events.

Grade 3
GroupValue95% CI
Arm 1- Safety Run-in Dose Level 10
Grade 4
GroupValue95% CI
Arm 1- Safety Run-in Dose Level 10
Grade 5
GroupValue95% CI
Arm 1- Safety Run-in Dose Level 10
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Secondary · Date treatment consent signed to date off study, approximately 13 months and 24 days.

Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent

GroupValue95% CI
Arm 1- Safety Run-in Dose Level 12

Adverse events — posted to ClinicalTrials.gov

Time frame: Date treatment consent signed to date off study, approximately 13 months and 24 days.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Arm 1- Safety Run-in Dose Level 1
Serious: 1/2 (50%)
Deaths: 2/2

Serious adverse events (2 terms)

ReactionSystemArm 1- Safety Run-in Dose …
Abdominal painGastrointestinal disorders
Creatinine increasedInvestigations
Other adverse events (26 terms — click to expand)

ReactionSystemArm 1- Safety Run-in Dose …
Alanine aminotransferase increasedInvestigations
Alkaline phosphatase increasedInvestigations
AnemiaBlood and lymphatic system disorders
AnorexiaMetabolism and nutrition disorders
Aspartate aminotransferase increasedInvestigations
Back painMusculoskeletal and connective tissue disorders
ChillsGeneral disorders
ConstipationGastrointestinal disorders
Creatinine increasedInvestigations
DehydrationMetabolism and nutrition disorders
Disease progressionGeneral disorders
DyspepsiaGastrointestinal disorders
FatigueGeneral disorders
FeverGeneral disorders
Flu like symptomsGeneral disorders
HypercalcemiaMetabolism and nutrition disorders
HypertensionVascular disorders
HypoalbuminemiaMetabolism and nutrition disorders
HyponatremiaMetabolism and nutrition disorders
NauseaGastrointestinal disorders
PainGeneral disorders
ProteinuriaRenal and urinary disorders
Rash maculo-papularSkin and subcutaneous tissue disorders
Thyroid stimulating hormone increasedInvestigations
VomitingGastrointestinal disorders
Weight gainInvestigations

Most-reported serious reactions: Abdominal pain, Creatinine increased.

Data from ClinicalTrials.gov NCT04150562 adverse events section.

Sponsor's own description

Background: -Clear-cell renal cell carcinoma (ccRCC) is a kind of kidney cancer. The drug avelumab may help direct the immune response to the tumors and can prolong the immune response. The drug Interleukin-15 (IL-15) stimulates certain kinds of white blood cells that have the potential to attack the cancer. Objective: -To test whether IL-15 and avelumab administered together are safe and effective at treating ccRCC. Eligibility: -People ages 18 and older with relapsed, metastatic biopsy proven clear cell renal cell carcinoma (ccRCC) that has not responded to standard treatments Design: Participants will be screened with: * Medical history * Physical exam * Blood, urine, heart, and lung tests * Computed tomography (CT) and positron emission tomography (PET) scans and possible MRI: Participants will lie in a machine that takes pictures of the body. For the CT scan, they may receive an oral contrast agent by mouth and normally receive IV contrast through a vein to improve the x-ray images. * Tumor sample to confirm expression of avelumab target: If one is not available, participants will require a new biopsy that is generally obtained by a needle that is inserted into the tumor. Participants will get the study drugs by vein for up to four 28-day cycles. The IL-15 will be given through a vein continuously for the first 5 days (120 hours) of each cycle. They avelumab will be given through a vein over about 1 hour on days 8 and 22 of each cycle. Participants will be hospitalized for their 1st week of IL-15 cycle and may be able to receive their subsequent IL-15 treatment as an outpatient depending on their side effects. Participants who receive the infusion as an outpatient will return to the hospital each day for a new bag of IL-15. Participants who cannot or do not want to be treated as an outpatient will be treated in the hospital during their 5-day IL-15 infusions. * Participants will need a midline venous catheter which is longer than a standard venous catheter but is still inserted into a peripheral vein in their arm. * Participants will have repeats of blood tests to monitor the blood counts and chemistry throughout the study. * Participants will have follow-up visits 30 days after their last treatment, every 60 days for the first 6 months, every 90 days for 2 years, then every 6 months.

Publications & conference data

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

  1. IL-15 in the Combination Immunotherapy of Cancer.
    Waldmann TA, Dubois S, Miljkovic MD, Conlon KC. · · 2020 · cited 187× · PMID 32508818 · DOI 10.3389/fimmu.2020.00868
  2. Immunomodulatory Effects of IL-2 and IL-15; Implications for Cancer Immunotherapy.
    Yang Y, Lundqvist A. · · 2020 · cited 149× · PMID 33266177 · DOI 10.3390/cancers12123586
  3. Interleukin 15 in Cell-Based Cancer Immunotherapy.
    Zhou Y, Husman T, Cen X, Tsao T, et al · · 2022 · cited 68× · PMID 35806311 · DOI 10.3390/ijms23137311
  4. Therapeutic potential of interleukin-15 in cancer (Review).
    Isvoranu G, Surcel M, Munteanu AN, Bratu OG, et al · · 2021 · cited 39× · PMID 33986840 · DOI 10.3892/etm.2021.10107
  5. Interleukin-15 augments NK cell-mediated ADCC of alemtuzumab in patients with CD52+ T-cell malignancies.
    Miljkovic MD, Dubois SP, Müller JR, Bryant B, et al · · 2023 · cited 17× · PMID 35475910 · DOI 10.1182/bloodadvances.2021006440
  6. PD-1/PD-L1 inhibitors-based treatment for advanced renal cell carcinoma: Mechanisms affecting efficacy and combination therapies.
    Ding L, Dong HY, Zhou TR, Wang YH, et al · · 2021 · cited 15× · PMID 34382349 · DOI 10.1002/cam4.4190
  7. IL15 and Anti-PD-1 Augment the Efficacy of Agonistic Intratumoral Anti-CD40 in a Mouse Model with Multiple TRAMP-C2 Tumors.
    Chen W, Bamford RN, Edmondson EF, Waldmann TA. · · 2022 · cited 13× · PMID 35262675 · DOI 10.1158/1078-0432.ccr-21-0496
  8. IL15 synergizes with radiotherapy to reprogram the tumor immune contexture through a dendritic cell connection.
    Pilones KA, Charpentier M, Garcia-Martinez E, Demaria S. · · 2020 · cited 8× · PMID 32934886 · DOI 10.1080/2162402x.2020.1790716

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