Kidney Cancer Journal 123
CR) in the nivolumab+ipilimumab group and 19.2% (no
CR) in the sunitinib group. Median PFS and OS were 8.4
months and 31.2 months in the nivolumab+ipilimumab
group, respectively, and 4.9 months and 13.6 months in
the sunitinib group, respectively. These exploratory
analyses show a remarkable efficacy of checkpoint blockade
combination in the treatment of this generally treatment
refractory disease, with similar safety profile to the
general study population.
Phase 1b Study of Cabozantinib in Combination
with Atezolizumab by Dr Neeraj Agarwal
Dr Agarwal described the COSMIC-021 phase 1b study
using first-line cabozantinib+atezolizumab in 12 patients
with metastatic RCC (10 ccRCC, 2 nccRCC). This combination
was noted have an acceptable safety profile and
promising activity with responses in 8 of 10 patients
with ccRCC.
Second-Line VEGF Receptor TKI Outcomes
afer First-Line Immune Checkpoint Bloackade
in mRCC by Dr Ritesh Kotecha
Dr Kotecha reported on a retrospective study from 2 cancer
centers whereby VEGFR TKI was used as second line
therapy in 70 patients who had already received checkpoint
inhibitors as first line therapy. The authors report
an ORR of 41.2%, with 52.9% SD. Median PFS was 13.2
months (1-year PFS 52.5%) and median OS was not
reached (1-year OS 79.6%). Second line VEGFR TKI median
duration was 10.1 months, with 47% of patients
discontinuing therapy due to PD. The authors have
demonstrated in this cohort that tolerability was similar
to first line therapy historic controls and that second line
VEGFR TKI can be safely used after first line checkpoint
inhibitors, with good outcomes.
Ipilimumab plus Nivolumab as Salvage
Therapy in Patients with Immunotherapy-
Refractory mRCC by Dr Kimberly Allman
Dr Allman reported on a retrospective study from 2 cancer
centers whereby ipilimumab+nivolumab was used as
second line therapy in 14 patients who had already received
other checkpoint inhibitors as first line therapy,
and showed that ipilimumab+nivolumab was well-tolerated
in this setting, and generated a 33% PR rate. Additional
centers are being recruited into this project in
order to increase the size of this retrospective study.
The Next 10 years: The Next Therapeutic Targets
This session included 5 different presentations covering
early phase clinical trials of novel therapeutics being investigated
in patients with RCC.
• Dr Ranjit Bindra discussed oncometabolite-induced
homologous recombination suppression (IDH1/2, FH,
and SDH mutants), and its targeting in solid tumors,
with a focus on the PARP inhibitors olaparib and
BGB290, alone or in combination with established
therapies.
• Dr Abhishek Tripathi discussed the rationale behind
using adenosine pathway inhibitors (Anti-CD73 and
Adenosine 2a Receptor antagonists) in patients with
RCC. One phase 1 trial has studied CPI-444 (A2aR antagoinst)
in combination with atezolizumab in 30 patients
with RCC refractory to anti-PD-1 therapy. Other
trials of anti-CD73 and A2aR antagonists are planned,
in combination with checkpoint inhibitor therapy, in
patients with metastatic RCC.
• Dr Thomas Powles delineated the biology and roles of
TGFb in differentiation and immune inhibition, along
with data in RCC suggesting TGFb is overexpressed in
patients with poor prognosis. Dr Powles also discussed
data on targeting both PD-L1 and TGFb to enhance
the efficacy and infiltration of T cells into immune excluded
tumors. This could be done either with a combination
of a TGFb-R1 kinase inhibitor (Galunisertib)
with a PD-L1 inhibitor, or with a novel fusion protein
(M7824) that consists of an IgG1 monoclonal antibody
against PD-L1 with a TGFb trap.
• Dr Thai Ho focused on treatment of patients with
SETD2-deficient tumors, and described a phase 2 study
of adavosertib (AZD1775) to target nucleotide metabolism
in patients with these tumors.
• Dr Toni Choueiri described a phase 1 study that will
be using a new personalized neoantigen peptide vaccine
NeoVax (in combination with local injection of
ipilimumab) in 20 patients with fully resected stage III
RCC or with M1 that is completely resected with subsequent
absence of disease. KCJ