Aldesleukin and Pembrolizumab in Treating Patients With Advanced or Metastatic Kidney Cancer

NCT03260504 | Terminated Phase 1 Results DMC FDA Drug

• 3 other identifiers: 9611NCI-2017-01416RG1717068
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of aldesleukin when given together with pembrolizumab in treating patients with kidney cancer that has spread to other parts of the body. Aldesleukin may stimulate white blood cells to kill kidney cancer cells. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to avoid recognition by immune cells. Giving aldesleukin and pembrolizumab may work better in treating patients with kidney cancer.

Conditions

Advanced Clear Cell Renal Cell Carcinoma; Stage IV Renal Cell Cancer; Stage III Renal Cell Cancer; Metastatic Clear Cell Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Number of Adverse Events

  The safety analysis was based on subjects who experienced toxicities as defined by CTCAE v5.0 criteria. Safety was assessed by quantifying the toxicities and laboratory abnormalities by grades experienced, including any serious adverse events (SAEs). Only treatment-related adverse events with an incidence rate of at least 2.5% are reported.

  Adverse events were recorded from the time the consent form was signed through 30 days following the cessation of the study treatment for each participant. Each treatment course was 12 weeks and the maximum duration of treatment was 3 courses (36 weeks).

Secondary Outcomes (3)

• Number of Participants With Objective Response

  Tumor imaging was collected at baseline after consent was obtained, every 12 weeks at end of a treatment course (max. 3 courses), and every 12 weeks after the cessation of study treatment for up to 1 year of surveillance follow-up for each participant.

• Number of Participants With Objective Response or Stable Disease

  Tumor imaging was collected at baseline after consent was obtained, every 12 weeks at end of a treatment course (max. 3 courses), and every 12 weeks after the cessation of study treatment for up to 1 year of surveillance follow-up for each participant.

• Progression Free Survival (PFS)

  Tumor imaging was collected at baseline after consent was obtained, every 12 weeks at end of a treatment course (max. 3 courses), and every 12 weeks after the cessation of study treatment for up to 1 year of surveillance follow-up for each participant.

Study Arms (1)

Treatment (pembrolizumab, aldesleukin)

EXPERIMENTAL

Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Patients also receive aldesleukin subcutaneously (SC) 5 days per week for 6 weeks; or aldesleukin IV on days 2-6 of pembrolizumab cycles 1 and 2. Pembrolizumab treatment repeats every 3 weeks for 4 cycles per treatment course in the absence of clinical disease progression or unacceptable toxicity.

Biological: Aldesleukin; Biological: Pembrolizumab

Interventions

Aldesleukin BIOLOGICAL

Given SC or IV

Also known as: 125-L-Serine-2-133-interleukin 2, Proleukin, r-serHuIL-2, Recombinant Human IL-2, Recombinant Human Interleukin-2

Treatment (pembrolizumab, aldesleukin)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475, Immunoglobulin G4, Anti-(Human Programmed Cell Death 1)

Treatment (pembrolizumab, aldesleukin)

Eligibility Criteria

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

You may qualify if:

• Be willing and able to provide written informed consent for the trial
• Be \>= 18 years of age on day of signing informed consent
• Have histologic confirmation of RCC with a clear cell component
• Have advanced (not amenable to potentially curative surgery) or metastatic RCC
• May have received previous systemic treatments or regimens for metastatic RCC. Prior therapy can include checkpoint blocking antibodies targeting PD-1, PD-L1, or cytotoxic Tlymphocyte-associated antigen-4 (CTLA-4) and/or targeted agents including TKIs, mTOR inhibitors, or bevacizumab. Patients may choose to receive study treatment as their initial therapy
• Previously treated patients must have documented disease progression after their last line of therapy
• Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Available tissue from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
• Absolute neutrophil count (ANC) \>= 1,500 /mcL (within 14 days of treatment initiation)
• Platelets \>= 100,000/mcL (within 14 days of treatment initiation)
• Hemoglobin \>= 9 g/dL or \>= 5.6 mmol/L (within 14 days of treatment initiation)
• Serum creatinine =\< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate \[GFR\] can also be used in place of creatinine or CrCl) \>= 40 mL/min for subject with creatinine levels \> 1.5 X institutional ULN; creatinine clearance should be calculated by Cockcroft-Gault (within 14 days of treatment initiation)
• Serum total bilirubin =\< 1.5 X ULN OR direct bilirubin =\< ULN for subjects with total bilirubin levels \> 1.5 ULN (within 14 days of treatment initiation)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) =\< 2.5 X ULN OR =\< 5 X ULN for subjects with liver metastases (within 14 days of treatment initiation)

You may not qualify if:

• Has received prior therapy with IL-2 or other investigational systemic cytokine therapy signaling through a common gamma-chain cytokine receptor including IL-7, IL-15 or IL-21
• Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment
• Has had a prior monoclonal antibody within 4 weeks prior to study day I. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1
• Adverse events due to prior treatment must be resolved to \< grade 1
• \* Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
• For patients previously treated with checkpoint blocking antibodies, no history of myocarditis, pneumonitis or nephritis of any grade associated with the prior treatment
• Has had autoimmune toxicity associated with prior checkpoint blocking antibodies requiring more than one drug class of immune suppressive therapy to resolve (e.g. steroid-refractory toxicity requiring infliximab, mycophenolate mofetil, tacrolimus or other immune suppressive agent) or requiring continuous immune suppression \> 12 weeks, or having a severity judged to be life threatening by the investigator
• Has a known additional malignancy that is progressing or requires active treatment; exceptions include locally curable cancers such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ of the cervix or breast that has undergone potentially curative therapy
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
• (Dose level 1) subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment
• (Dose Level 2 and 3) subjects may not have any history of or current CNS metastases; baseline imaging of the brain is required within 28 days prior to the start of study treatments
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
• Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents; subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule; subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study; subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study
• Has history of (non-infectious) pneumonitis that required steroids or active, non-infectious pneumonitis
• Ongoing symptomatic cardiac dysrhythmias, uncontrolled atrial fibrillation, or prolongation of the corrected QT interval defined as \> 450 msec for males and \> 470 msec for female

Sponsors & Collaborators

• University of Washington: lead
• Merck Sharp & Dohme LLC: collaborator
• Prometheus Laboratories: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell; Clear-cell metastatic renal cell carcinoma

Interventions

aldesleukin; pembrolizumab; Immunoglobulin G

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)

Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Study enrollment was hampered by changes in frontline treatment options for advanced/metastatic RCC. There was a significant decrease of IL-2 therapy use at our cancer center starting in 2018 which coincided with the FDA approval of ICI-based regimens of nivolumab plus ipilimumab (2018), and pembrolizumab plus axitinib (2019). Study enrollment was also affected by the COVID-19 pandemic as our hospital prioritized efforts to inpatient care for patients with COVID-19 versus elective use of IL-2.

Results Point of Contact

• Title: Scott Tykodi, MD, PhD
• Organization: University of Washington

stykodi@fredhutch.org

206-606-7763

Study Officials

• Scott S. Tykodi

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: August 21, 2017
• First Posted: August 24, 2017
• Study Start: August 28, 2018
• Primary Completion: July 26, 2022
• Study Completion: July 26, 2022
• Last Updated: December 8, 2025
• Results First Posted: December 8, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)