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

NCT04150562 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 20000720-C-0007
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Clear-Cell Renal Carcinoma

Keywords

Antibody Dependent Cellular Cytotoxicity (ADCC); Anti-PD-L1 monoclonal antibody

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (Complete Response + Partial Response)

  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 determinations of partial response (PR - e.g., 30% decrease of target lesions) or better at least 4 weeks apart and before irPD (and not qualifying for an irCR).

  Following start of study medication while on treatment, approximately 2 months.

Secondary Outcomes (4)

• Duration of Response

  Following start of study medication while on treatment, up to 1-2 months.

• Progression-free Survival

  Monitoring frequency is every two cycles through completion of study then annually until progressive disease is noted, an average of 73 days.

• Overall Survival

  time from the date of study enrollment until time of death from any cause, an average of 167 days

• Number of Grade 3 Adverse Events Possibly, Probably or Definitely Related to Treatment of rhIL-15 + Avelumab

  4 cycles (each cycle is 28 days), up to 112 days

Other Outcomes (1)

• Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0).

  Date treatment consent signed to date off study, approximately 13 months and 24 days.

Study Arms (2)

Arm 1- Experimental Treatment: Safety Run-in

EXPERIMENTAL

Interleukin 15 (IL-15) by continuous intravenous (CIV) infusion at escalating doses of 2 and 4 mcg/kg/day on days 1-5 of each 28-day cycle (max 4 cycles) with avelumab by intravenous (IV) infusion at a dose of 800mg on Day 8 and 22 of each cycle

Drug: rhIL-15; Biological: Avelumab

Arm 2-Experimental Treatment: Dose Expansion

EXPERIMENTAL

Interleukin 15 (IL-15) by continuous intravenous (CIV) infusion at 4 mcg/kg/day on days 1-5 of each 28- day cycle (max 4 cycles) with avelumab by intravenous (IV) infusion at a dose of 800mg on Day 8 and 22 of each cycle

Drug: rhIL-15; Biological: Avelumab

Interventions

rhIL-15 DRUG

Recombinant human Interleukin-15 (rhIL-15) will be administered by continuous intravenous infusion (CIV) at a starting dose of 2 mcg/kg/day for the first dose level followed by a second dose level of 4mcg/kg/day on days 1-5 of the 28-day cycle of each of four cycles.

Also known as: Recombinant human Interleukin-15

Arm 1- Experimental Treatment: Safety Run-in; Arm 2-Experimental Treatment: Dose Expansion

Avelumab BIOLOGICAL

avelumab (800mg by intravenous (IV) will be administered on days 8 and 22 of the 28- day cycle for four cycles

Also known as: Bavencio

Arm 1- Experimental Treatment: Safety Run-in; Arm 2-Experimental Treatment: Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically proven metastatic clear cell renal carcinoma with greater than or equal to 5% expression of programmed death-ligand 1 (PD-L1) on the tumor cells confirmed by immunohistochemistry (IHC) in the national Cancer Institute (NCI) Lab of Pathology. Archival tumor sample may be used but if archival tissue is not available or is not adequate, tissue biopsy will be required.
• Patients must have failed or relapsed and have progressive disease after at least 2 prior therapies that include multityrosine kinase inhibitor (mTKI) like axitinib or sunitinib and an anti-Programmed cell death protein 1 (PD1) or PD-L1 (ICI) therapy like nivolumab which could have been administered in combination with an anti-cluster of differentiation 152 (CTLA4) agent like ipilimumab. Patients who received an immune checkpoint inhibitor (ICI) in combination with a mTKI would be eligible for the trial if they received another appropriate treatment. Adjuvant or neoadjuvant with either type of agent would not fulfill this requirement only treatment for metastatic disease will be considered to satisfy this criterion.
• Disease must be measurable with at least one measurable lesion by the Response Evaluation Criteria in Solid Tumors (Recist) v1.1 criteria that is different from the lesion biopsied.
• Age \>=18 years
• NOTE: Because no dosing or adverse event data are currently available on the use of recombinant human Interleukin-15 (rhIL-15) in combination with avelumab in patients \<18 years of age, children are excluded from this study, but may be eligible for future pediatric trials
• Eastern Cooperative Oncology Group (ECOG) performance status \<= 1 (Karnofsky \>=80%)
• Adequate organ and marrow function as defined below:
• absolute neutrophil count greater than or equal to 1,500/mcL
• absolute lymphocyte count greater than or equal to 500/mcL
• Hemoglobin greater than or equal to 10 g/dL
• Platelets greater than or equal to 100,000/mcL
• total bilirubin less than or equal to 1.5 X institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT)/Alanine aminotransferase (ALT) Serum glutamic pyruvic transaminase (SGPT) less than or equal to 2.5 X institutional ULN
• Serum creatinine less than or equal to 1.5 X institutional ULN
• Creatinine clearance greater than or equal to 50 mL/min/1.73 m\^2 for patients with creatinine levels \>1.5 institutional ULN

You may not qualify if:

• Chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C).
• Persisting toxicity related to prior therapy of grade \> 1, with the exception of the following: alopecia, sensory neuropathy grade \<= 2, or other grade \<= 2 not constituting a safety risk based on investigator's judgement.
• Patients who are receiving any other investigational agents
• Current use of immunosuppressive medication, EXCEPT for the following:
• Intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection)
• Systemic corticosteroids at physiologic doses \<= 10 mg/day of prednisone or equivalent; or,
• Steroids as premedication for hypersensitivity reactions (e.g., computed tomography (CT) scan premedication).
• Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• Patients with previous malignant disease other than the target malignancy within the last 5 years with the exception of basal or squamous cell carcinoma of the skin or cervical carcinoma in situ.
• Patients with history of any organ transplantation
• Vaccination within 4 weeks of the first dose of avelumab. Vaccination with a live vaccine while on trial is prohibited.
• NOTE: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed.
• Patients with history of allergic reactions attributed to compounds of similar chemical or biologic composition to rhIL-15 or avelumab.
• Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring systemic therapy, or psychiatric illness/social situations that would limit compliance with study requirements.
• Inability or refusal to practice effective contraception during therapy or the presence of pregnancy or active breastfeeding. Based on its mechanism of action, avelumab can cause fetal harm when administered to a pregnant woman. Animal studies have demonstrated that inhibition of the PD-1/PD-L1 pathway can lead to increased risk of immune-mediated rejection of the developing fetus resulting in fetal death. These potential risks may also apply to other agents used in this study.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• Waldmann TA, Dubois S, Miljkovic MD, Conlon KC. IL-15 in the Combination Immunotherapy of Cancer. Front Immunol. 2020 May 19;11:868. doi: 10.3389/fimmu.2020.00868. eCollection 2020.

  PMID: 32508818 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Interleukin-15; avelumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Dr. Kevin C. Conlon
• Organization: National Cancer Institute

conlonkc@mail.nih.gov

240-858-3570

Study Officials

• Kevin C Conlon, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 1, 2019
• First Posted: November 4, 2019
• Study Start: May 26, 2020
• Primary Completion: July 23, 2021
• Study Completion: September 16, 2021
• Last Updated: May 17, 2022
• Results First Posted: May 17, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data will be available during the study and indefinitely.
• Access Criteria: Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI).

Locations

US (1)