discussed as well, and will be described in more detail
below.
A Phase II Trial of Intermittent Nivolumab in
Patients with mRCC Who Have Received Prior
Anti-Angiogenic Therapy by Dr Moshe Ornstein
Dr Ornstein described an ongoing phase 2 clinical trial
(target 40 patients, any RCC, 14 patients enrolled) that
is studying the feasibility of using intermittent nivolumab
in patients with metastatic RCC who received
prior anti-angiogenic therapy. Patients receive 12 weeks
of nivolumab. If patients experience PD, they come off
therapy/trial. If the tumor burden decreases by 10% or
more, they go to the intermittent phase. If the tumor
burden decreases by less than 10%, they continue
nivolumab.
For the intermittent phase, patients hold nivolumab
for 12 weeks and are reassessed. If tumor burden increases
by 10% or more, patients resume nivolumab until
PD or tumor burden reduction by 10% or more. If PD,
they come off therapy/trial, and if tumor burden decreases
by 10% or more, they can hold nivolumab. If
after 12 weeks of nivolumab hold, patients do not have
an increase of tumor burden of more than 10%, they can
continue to hold nivolumab for another 12 weeks and
get reassessed.
Using Cryotherapy to Stimulate the Immune
System in RCC by Dr Matthew Campbell
Dr. Campbell presented an ongoing pilot study in
metastatic RCC (target 30 patients, any RCC, 29 enrolled)
where patients are randomized to either 2 doses
of tremelimumab followed by surgery or biopsy, or to
cryoablation of a metastatic site, followed by 2 doses of
tremelimumab followed by surgery or biopsy. Patients
then continue tremelimumab until PD. Preliminary immune
correlate analysis has shown an increase in CD3+
T cells in patients with ccRCC who received cryotherapy,
as well as an increase in the frequency of an ICOS+ CD8+
T-cell subset, and that VEGF and IFN pathway genes are
significantly higher in patients with ccRCC compared to
nccRCC.
Rationally Targeting the Bone with Radium
Pus Cabozantinib by Dr. Rana McKay
Dr McKay described a new clinical trial (RADICAL) for
patients (target 132 patients) with any RCC histology
with 2 or more untreated bone metastases, where patients
are randomized to either cabozantinib alone or
cabozantinib+Radium-223, with primary endpoint being
symptomatic skeletal event-free survival.
Trials in Progress - PDIGREE by Dr Tian Zhang
Dr Zhang presented the PDIGREE trial (Alliance
A031704), which should be starting in 2019. PDIGREE
plans to enroll 1044 patients with mRCC where all patients
receive nivolumab+ipilimumab for 4 doses. In case
of CR, patients continue with nivolumab alone. If case
of PD, patients switch to cabozantinib. Patients with
PR/SD (around 696 patients) will be randomized to
nivolumab alone or nivolumab+cabozantinib. The primary
endpoint is 3-year overall survival, with key secondary
122 Kidney Cancer Journal
endpoints such as 1-year CR rate, PFS, ORR and
toxicity of combination therapy. Correlative studies are
planned and will include using tissue-based markers (PDL1
and MET IHC, tumor mutational burden and neoantigen
load, gene expression profiling, TILs), circulating
markers (IL-6 and other cytokines, ctDNA), quality of life
measures, and imaging correlates.
Treatment-Free Internval Following
Discontinuation of First-Line Nivolumab
Plus Ipilimumab or Sunitinib in Patients
with Advanced RCC by Dr Thomas Powles
Dr Powles described a posthoc analysis of CheckMate
214 studying treatment-free survival (TFS) after discontinuation
of nivolumab+ipilimumab or sunitinib. Only
patients with IMDC intermediate/poor-risk were included.
The study demonstrated that the combination
therapy delayed time from randomization to second-line
therapy by almost 7 months compared with sunitinib.
Time from randomization to second-line therapy and
TFS analyses showed durable response/disease control
with combination therapy despite treatment discontinuation.
Delay to second-line treatment and TFS benefit
with combination therapy compared with sunitinib was
noted regardless of whether patients achieved objective
response or disease control, and regardless of baseline
tumor PD-L1 expression. Dr Powles noted that a full TFS
analysis of CheckMate 214 is being performed, and will
include the intention-to-treat analysis and favorable-risk
patients.
Safety and Activity of Immune Checkpoint
Inhibitors in Patients with Advanced RCC
and Pre-existing Autoimmune Disorders
by Dr Nieves Martinez Chanza
Dr. Martinez Chanza reported on a retrospective study
that included 25 patients with well-controlled autoimmune
disorders (AD) treated with checkpoint inhibitors.
CTCAE grade 1/2 and 3/4 AD exacerbations were noted
in 6 and 2 patients, respectively, while CTCAE grade 1/2
and 3/4 immune-related adverse events (irAE) were
noted in 10 and 2 patients, respectively. 1 patient received
systemic corticosteroids for AD exacerbation and
4 patients for new irAE. Ultimately, 1 patient discontinued
checkpoint inhibitor therapy due to AD exacerbation
and 2 for irAE. Median follow up in this study was
15 months, with median time from checkpoint inhibitor
therapy to AD exacerbation or to new irAE of almost 3
months. Overall response rate was 44% and 2-year OS
was 54% in this small cohort. The authors concluded
that while some patients with AD could benefit from
checkpoint inhibitor therapy, there is a risk for AD exacerbation
and new irAEs, which are manageable, but require
careful monitoring and multidisciplinary care.
CheckMate 214 Retrospective Analyses
by Dr Nizar Tannir
Dr Tannir described a posthoc analysis of CheckMate 214
focusing on the outcomes of 112 patients (intermediate/
poor-risk) with sarcomatoid dedifferentiation treated
with either nivolumab+ipilimumab (60 patients) or sunitinib
(52 patients). Confirmed ORR was 56.7% (18.3%