Kidney Cancer Journal 105
Revisiting IL-2 Therapy in Renal Cell Carcinoma:
A Case Report of a Patient Treated With
Pegylated IL-2, Bempegaldesleukin (NKTR-214)
Elshad Hasanov,
MD, PhD
Nizar M. Tannir,
MD, FACP
Department of Genitourinary Medical Oncology
Division of Cancer Medicine
MD Anderson Cancer Center,
Houston, Texas
This cohort in PIVOT-02 is ongoing and full data analyses
for the cohort are not yet available. Therefore, this patient
case should be interpreted with caution.
Abstract
IL-2 is a well-known stimulatory cytokine involved in
differentiation and activation of T-cells and natural killer
(NK) cells. FDA approved high-dose IL-2, aldesleukin for
the treatment of metastatic renal cell carcinoma (mRCC)
in 1992 based on the phase 2 trial that showed 7% complete
response and 15% overall response rate.1 However,
due to its severe toxicities, such as vascular leak syndrome,
pulmonary edema, and cardiac toxicity, that required
inpatient administration, it has limited use. After
the discoveries of immune checkpoint inhibitors (CPI),
the treatment landscape of mRCC has rapidly evolved.
Different combinations of CPI or with tyrosine kinase inhibitors
(TKI) have been approved for first-line treatment.
Despite that, achieving a durable response or
overcoming resistance to CPI therapy is an unmet medical
need. Revisiting IL-2 therapy and combining with CPI
may overcome this and achieve better and more durable
responses.
Bempegaldesleukin (BEMPEG; NKTR-214) is a CD122-
preferential IL-2 pathway agonist that has been shown
to increase tumor-infiltrating lymphocytes (TIL), T-cell
clonality and PD-1 expression2,3 (Figure 1). With its prodrug
design, BEMPEG achieves rapid and sustained activation
of the IL-2 pathway, and minimizes toxicity vs
native IL-2 allowing for administration in an outpatient
setting.2 Additionally, BEMPEG combined with the CPI
nivolumab (NIVO) has been shown to convert baseline
tumors from PD-L1 negative (<1%) to PD-L1 positive
(1%).4,5 PIVOT-02 (NCT02983045) is a phase 1/2 study
of BEMPEG in combination with NIVO and other anticancer
therapies in patients with advanced solid tumors.
Here we present a clinical vignette of a patient who was
successfully treated with BEMPEG plus NIVO as part of
the PIVOT-02 trial. Some details have been modified to
protect the privacy of the individual.
Case Report
Mr. F is a 50 to 55 year-old man who initially presented
with sudden onset gross hematuria and was found to
have a 7cm right renal mass. He underwent laparoscopic
right radical nephrectomy and pathology revealed clear
cell RCC, pT3a N0 M0, Fuhrman grade 2. He was initially
treated on a phase 2 randomized single-blind study of
Vitespen (HSPPC-96, Oncophage) for immune response
assessment following treatment of patients with resectable
RCC at intermediate risk for recurrence. He was followed
up with CT chest, abdomen, and pelvis every 3,
then 6 and 12 months.
He did not have any evidence of recurrence until 6
years after the nephrectomy, when restaging CT showed
a 2 x 3cm hypervascular lesion at the pancreatic tail and
multiple subcentimeter bilateral pulmonary nodules
concerning for metastasis. Endoscopic ultrasound-guided
fine-needle aspiration of the pancreas lesion showed metastatic
clear cell RCC. Based on the International Metastatic
RCC Database Consortium (IMDC) risk strati-
fication, he was categorized as having favorable-risk
disease. Mr. F enrolled on the PIVOT-02 trial. His PD-L1
status at baseline was PD-L1 negative, and his initial baseline
SLD was 55mm. The patient was enrolled during
the dose escalation phase, where he received BEMPEG
0.003mg/kg and NIVO 240mg every 2 weeks. After 8
months, his dose of BEMPEG was increased to the recommended
Phase 2 dose, 0.006mg/kg, and the NIVO increased
to 360 mg every 3 weeks. At week 16, the patient
Keywords: IL-2 therapy, nivolumab, bempegaldesleukin, immune
checkpoint inhibitors, renal cell carcinoma, combination therapy.
Corresponding Author: Nizar M. Tannir, MD, FACP, Ransom Horne, Jr.,
Professor of Cancer Research, Professor and Chair ad interim
Department of Genitourinary Medical Oncology, Division of Cancer
Medicine, MD Anderson Cancer Center, 1515 Holcomb Blvd., Unit
1374, Houston, TX 77030-4009 Email: ntannir@mdanderson.org
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