66 Kidney Cancer Journal
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Positive Topline Results Achieved in
Randomized Phase 2 ENTRATA Study of
Telaglenastat with Everolimus in RCC
• Doubled median progression-free survival (PFS) in heavily
pre-treated patients with advanced renal cell carcinoma
• Provides first clinical proof of concept for glutaminase
inhibitor telaglenastat
SOUTH SAN FRANCISCO, CA—Calithera Biosciences has
achieved positive results from its randomized placebo-
controlled Phase 2 ENTRATA study of telaglenastat (CB-
839) in combination with everolimus in patients with
advanced RCC. The combination doubled the median progression
free survival (PFS) in heavily pre-treated patients
with advanced RCC and had a well-tolerated safety profile.
Telaglenastat is the first glutaminase inhibitor to demonstrate
clinical activity for the treatment of cancer.
“The achievement of positive topline results in our first
randomized trial is a significant milestone because it provides
clinical proof of concept for telaglenastat,” said Susan
Molineaux, PhD, president and chief executive officer of
Calithera. “This study demonstrates a clinically meaningful
improvement in progression free survival in patients with
advanced renal cell carcinoma who have been treated with
many prior lines of therapy, including immunotherapy and
multiple tyrosine kinase inhibitors. “
Patients enrolled were heavily pre-treated with a median
of three prior lines of therapy for advanced metastatic
disease including 70% with two or more prior tyrosine
kinase inhibitors (TKI), and 68% with intermediate/poor
MSKCC prognostic score. Eighty-eight percent of patients
received prior PD-1/PD-L1 therapy. Telaglenastat, when
added to everolimus, doubled the median PFS to 3.8
months as compared to 1.9 months for everolimus alone
and reduced the risk of disease progression or death by
36% (HR=0.64, P=0.079 one-sided). The primary endpoint
of the trial was PFS per investigator assessment with a
predetermined threshold of P≤0.2 one-sided. The secondary
endpoint of overall survival is not yet mature.
Frequency of all-grade adverse events in the telaglenastat
containing arm were comparable to that of everolimus
alone. Grade 3 or higher adverse events occurred in 80.4%
of patients in the telaglenastat plus everolimus arm versus
60.9% in the everolimus plus placebo arm. The most frequently
reported Grade ≥3 adverse events in the treatment
versus control arms, respectively, were anemia (17.4% vs.
17.4%), pneumonia (6.5% vs. 4.3%), abdominal pain (6.5%
vs. 0%), thrombocytopenia (6.5% vs. 0%), and fatigue (4.3%
vs. 8.7%). Adverse events leading to discontinuation of any
study drug were comparable (28.3% vs. 30.4%).
The ENTRATA trial (NCT03163667) is a randomized,
double-blind Phase 2 trial designed to evaluate the
efficacy and safety of telaglenastat in combination with
everolimus versus placebo with everolimus in patients with
advanced clear cell RCC who have been treated with at
least two prior lines of systemic therapy, including at least
one VEGFR-targeted TKI. Patients were stratified by prior
TKI treatment and MSKCC prognostic score. The trial enrolled
69 patients at multiple centers in the United States.
Calithera intends to present data at an upcoming medical
meeting. Telaglenastat is an investigational, novel glutaminase
inhibitor specifically designed to block glutamine
consumption in tumor cells. RCC tumors commonly exhibit
specific genetic alterations that cause cancer cells to
increase metabolism of glutamine. In preclinical studies,
telaglenastat produced synergistic antitumor effects when
used in combination with standard-of-care RCC therapies,
including everolimus and cabozantinib.
Telaglenastat is also being investigated in the CANTATA
trial, a global, randomized, double-blind Phase 2 trial designed
to evaluate the efficacy and safety of telaglenastat
in combination with cabozantinib versus placebo with
cabozantinib in patients with advanced clear cell RCC who
have been treated with one or two prior lines of systemic
therapy. CANTATA will enroll approximately 400 patients
and is designed with registrational intent. The primary
endpoint is PFS by blinded independent review. Calithera
expects data from this trial in the second half of 2020.
I
nternational Kidney Cancer Symposium
Scheduled for November 15-16
MIAMI—The 18th International Kidney Cancer Symposium,
featuring the most comprehensive agenda and program
focused on renal cell carcinoma, will be held November
15-16 at the Trump National Doral Miami Hotel. Researchers
and medical staff from leading centers worldwide
will gather for an exchange of ideas and information that
will frame future research and treatment of RCC.
Registration and full details on the agenda is available
online through the Association’s website,
kidneycancer.org.
Updated Overall Survival Hazard Ratio of 0.99
Reported in Phase 3 TIVO-3 Trial of Tivozanib in
Renal Cell Carcinoma
CAMBRIDGE, MA—AVEO Oncology has announced results
from the second prespecified analysis of overall survival
(OS) in the TIVO-3 trial. TIVO-3 is the Company’s Phase 3
randomized, controlled, multi-center, open-label study to
compare tivozanib (FOTIVDA®) to sorafenib in 350 subjects
with highly refractory metastatic renal cell carcinoma
(RCC). These results include an OS hazard ratio (HR) below
1.00, favoring tivozanib (HR=0.99; 95% CI: 0.76-1.29;
P=0.95). TIVO-3 is the first and only positive Phase 3 study
in third and fourth line RCC, and the first Phase 3 study in
RCC to investigate a predefined subpopulation of patients
who received prior immunotherapy, an emerging standard
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