New Study Compares Bempegaldesleukin (NKTR-214)
Plus Nivolumab to Sunitinib or Cabozantinib in
Previously Untreated Advanced RCC
CHICAGO – Bempegaldesleukin (NKTR-214) is a CD122-
preferential IL-2 pathway agonist that stimulates proliferation
and activation of tumor antien-specific CD8+ T cells
and natural killer cells within the tumor microenvironment
and increases PD-1/PD-L1 expression. These properties
make bempegaldesleukin (NKTR-214) a potentially promising
agent for combination therapy with checkpoint inhibitors
that target and inhibit the PD-1/PD-L1 pathway. In
phase 1 studies, NKTR-214 plus nivolumab demonstrated
encouraging objective response rates (ORR) in first-line
renal cell carcinoma (RCC) and an acceptable safety profile.
Immunotherapy with NKTR-214 plus nivolumab may lead
to greater clinical benefit than tyrosine kinase inhibitors
(TKIs), standard-of-care agents, in this patient population.
A multicenter, randomized, open-label phase 3 study
(NCT03729245) will evaluate the efficacy and safety of
bempegaldesleukin (NKTR-214) plus nivolumab compared
with investigator’s choice of TKI (sunitinib or cabozantinib)
in patients with previously untreated advanced or metastatic
RCC with clear cell component. Exclusion criteria include
active brain metastasis and autoimmune disease. Approximately
600 patients will be randomized in a 1:1 ratio, stratified
by PD-L1 status (≥1% vs < 1% or indeterminate),
International Metastatic RCC Database Consortium prognostic
score (1-2 intermediate risk vs 3-6 poor risk); and
TKI (sunitinib or cabozantinib; cabozantinib percentage
to be capped at 50%). Combination therapy will consist of
bempegaldesleukin (NKTR-214) 0.006 mg/kg intravenously
(IV) every 3 weeks (Q3W) plus nivolumab 360 mg IV Q3W
until progression or death or maximum of 2 years. TKI
therapy will consist of sunitinib 50 mg orally once daily
(QD) for 4 weeks followed by 2 weeks off or cabozantinib
60 mg orally QD. Primary objectives are ORR by blinded independent
central radiology (BICR) assessment and overall
survival. Secondary objectives are progression-free survival
by BICR, safety, predictive value of PD-L1 expression, and
quality of life. Enrollment is ongoing.
UT Southwestern Develops Test to Predict
Immunotherapy Response
DALLAS – A novel imaging test shows promise for identifying
kidney cancer patients most likely to benefit from immuno-
therapy. Investigators with the UT Southwestern Medical
Center Kidney Cancer Program say a new test can illuminate
kidney cancers that may respond to checkpoint inhibitors.
The strategy involved transforming an immunotherapy
drug, atezolizumab (Tecentriq), into a diagnostic tracer.
Atezolizumab binds to and disables PD-L1, a protein that
cancer cells display on their surface to shut off approaching
killer immune cells. By labeling atezolizumab with zirconium
89 (Zr89), a radioactive metal generated using a
cyclotron, the investigators were able to visualize atezolizumab
using PET (positron emission tomography). As
such, a single, very small dose of Zr89-atezolizumab can be
used to evaluate whether tumors deploy PD-L1 to suppress
immune cells and whether drugs disabling this pathway
may be effective.
58 Kidney Cancer Journal
Currently, immunotherapy drugs benefit less than 50
percent of kidney cancer patients. With immuno-PET, or
iPET, as a screening tool, the investigators hope to identify
those patients who will benefit. Marking the first time this
type of theranostic (drug turned into a diagnostic test) is
Left, illuminated tumor by iPET expressing immuno-
therapy target, compared to control tumor (right).
deployed for kidney cancer, the approach opens a molecular
window. In proof-of-principle experiments, a team led
by Dr James Brugarolas, one of the corresponding authors
of the study and the Director of the UT Southwestern
Kidney Cancer Program, showed that Zr89-atezolizumab
was able to illuminate kidney tumors with high levels of
PD-L1. As part of the study, investigators selected tumors
from two patients, one with high PD-L1 and another with
low PD-L1, and transplanted them into mice. The mice
were then injected with Zr89-atezolizumab intravenously
and evaluated by PET. As predicted from the mouse studies,
the patient with the high PD-L1 tumor had substantial
regression of his metastases when treated with nivolumab
(Opdivo), which targets the PD-L1 pathway.
“The development of tests predicting which patients
respond to immunotherapy is critical,” said Dr Hans
Hammers, an immunotherapy expert with the Kidney
Cancer Program. Zr89-atezolizumab was filed with the FDA
by the Cyclotron and Radiochemistry Program led by
Dr Xiankai Sun at UT Southwestern, also a corresponding
author of the study, and is now proceeding to evaluation
in patients in a clinical trial at UT Southwestern’s Harold C.
Simmons Comprehensive Cancer Center. The clinical trial
is made possible through a $600,000 translational award
to Dr. Brugarolas’ team by the V Foundation for Cancer
Research. Support for the preclinical studies was provided
through a Specialized Program of Research Excellence
(SPORE) grant from the National Cancer Institute. A second
trial also is planned at the Simmons Cancer Center using
Zr89-atezolizumab to evaluate the impact of stereotactic
body radiation therapy (SBRT) on PD-L1 expression in
kidney cancer patients. The SBRT trial will be funded by the
Kidney Cancer Congressionally Directed Medical Research
Program.
First Patient Enrolled in RCC Trial with Pexa-Vec
in Combination with Cemiplimab
SAN FRANCISCO— SillaJen, Inc., a clinical-stage, biotherapeutics
company focused on the development of oncolytic