Kidney Cancer Journal 41
MEDICAL INTELLIGENCE
Newsworthy, late-breaking information from Web-based
sources, professional societies, and government agencies
FDA approves nivolumab plus ipilimumab
combination for intermediate or poor-risk
advanced renal cell carcinoma
The Food and Drug Administration has granted approvals
to nivolumab and ipilimumab (Opdivo and Yervoy) in combination
for the treatment of intermediate or poor risk,
previously untreated advanced renal cell carcinoma (RCC).
Approvals were based on CheckMate 214 (NCT02231749),
a randomized open-label trial. Patients with previously
untreated advanced RCC received nivolumab (3 mg/kg)
plus ipilimumab (1 mg/kg) every 3 weeks for 4 doses
followed by nivolumab monotherapy (3 mg/kg) every
2 weeks, or sunitinib 50 mg daily for 4 weeks followed by
2 weeks off every cycle.
The trial demonstrated statistically significant improvements
in overall survival (OS) and objective response rate
(ORR) for patients receiving the combination (n=425) compared
with those receiving sunitinib (n=422). Estimated
median OS was not estimable in the combination arm compared
with 25.9 months in the sunitinib arm (hazard ratio
0.63, 95% CI: 0.44, 0.89; P<0.0001). The ORR was 41.6% (95%
CI: 36.9, 46.5) for the combination versus 26.5% (95% CI:
22.4, 31) in the sunitinib arm (P<0.0001). The recommended
schedule and dose for this combination is nivolumab,
3 mg/kg, followed by ipilimumab, 1 mg/kg, on the same
day every 3 weeks for 4 doses, then nivolumab, 240 mg,
every 2 weeks or 480 mg every 4 weeks.
Peloton Therapeutics initiates phase 2 trial of oral
HIF-2α inhibitor PT2977 for treatment of von Hippel-
Lindau Disease-associated kidney cancer
Peloton Therapeutics, Inc., announced dosing of the first
patient in a Phase 2 trial evaluating the efficacy and safety
of lead investigational oncology agent, PT2977, to treat
von Hippel-Lindau (VHL) disease-associated kidney cancer.
PT2977 is a once-daily, oral inhibitor of HIF-2α, a transcription
factor that has been implicated in the development
and progression of RCC. The primary objective of the Phase
2 trial is to evaluate the efficacy of PT2977 for the treatment
of VHL disease-associated renal tumors as measured by
overall response rate. Secondary objectives include duration
of response, time to response, progression free survival,
and time to surgery for VHL disease-associated renal
tumors. The trial will also evaluate the efficacy of PT2977
in other VHL disease-associated tumor types as well as the
safety and pharmacokinetics of PT2977. Patients will be
evaluated radiologically approximately every 12 weeks
while continuing in the study.
Peloton’s drug discovery and development efforts focus
on identifying novel compounds capable of modulating
complex protein-protein interactions that drive disease
which have eluded conventional small molecule
approaches. Peloton has the only clinical stage small-molecule
inhibitors of HIF-2α, and PT2977 has demonstrated a
favorable profile in a Phase 1 study in patients with advanced
solid tumors including RCC. The study will enroll
50 patients at clinical trial centers across the United States
and Europe. More information about the trial is available
at www.clinicaltrials.gov, identifier NCT NCT03401788.
First patient enrolled in phase 1 trial of INCB01158,
Keytruda combo for solid cancers
The first patient has been treated in a Phase 1 clinical trial
evaluating a combination of INCB01158 (aka CB-1158) plus
Keytruda (pembrolizumab) in patients with advanced solid
tumors, including RCC. The trial is evaluating the safety and
effectiveness of INCB01158, given alone or in combination
with an anti-PD-1 immune checkpoint inhibitor like
Keytruda. Developed by Calithera in collaboration with
Incyte Corporation, INCB01158 is an immunotherapy that
targets selectively the arginase enzyme.
Arginase is an enzyme produced in the tumor microenvironment
by immunosuppressive cells, like myeloidderived
suppressor cells (MDSCs). Its activity depletes the
amino acid arginine, which is essential for immune T-cells to
proliferate and survive. Inhibiting arginase is thus expected
to promote the T-cell expansion at the tumor site in cancers
where arginase-secreting MDSCs are known to play an
immunosuppressive role. These include renal cell cancer,
breast cancer, lung cancer, and acute myeloid leukemia.
Because INCB01158 increases the amount of T-cells within
the tumors, researchers believe it might work in synergy
with other immunotherapies that unleash T-cells’ tumorkilling
functions.
The Phase 1 trial (NCT02903914) is designed to assess
the safety of INCB01158 and define a recommended dose
to be used in planned Phase 2 studies, both as a monotherapy
and in combination with immune checkpoint therapy.
The study is being conducted in the U.S. and is expected
to include 236 patients with advanced or metastatic solid
tumors. Enrollment is ongoing.
Delayed mRCC targeted therapy does
not worsen survival
SAN FRANCISCO—Delayed rather than early initiation of
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/www.clinicaltrials.gov