were male (52.5%) and had ECOG PS of 0 (82.0%). The
most common lesions outside the kidney (non-RCC tumors)
were CNS hemangioblastomas (80.3%) and pancreatic
lesions (50.8%). Median (range) duration of
treatment was 9.9 mo (1.9-18.2) and 95.1% of pts remain
on therapy. Three pts discontinued (AE, n = 1; death
fentanyl toxicity, n = 1; pt decision, n = 1). There were
17 confirmed responses (ORR, 27.9% 95% CI, 17.1-
40.8%) and 8 (13.1%) unconfirmed (documented at 1
timepoint and to be confirmed at subsequent timepoint)
responses; all responses were PRs. Of 61 pts, 53 (86.9%)
had decrease in size of target lesions. In 17 pts with confirmed
response, median (range) DOR was not reached
(2.1-9.0 mo) and median (range) TTR was 5.5 mo (2.7-
14.0). Responses were also observed in CNS, retinal, and
pancreatic lesions. Median PFS was not reached; 12-mo
PFS rate was 98.3%. Treatment-related AEs (TRAEs) occurred
in 96.7% of pts, mostly grade 1 (44.3%) or grade
2 (42.6%) and primarily (20%) anemia (83.6%; considered
an on-target-toxicity), fatigue (49.2%), and dizziness
(21.3%). Grade 3 TRAEs occurred in 9.8% of pts, primarily
fatigue (4.9%) and anemia (3.3%). There were no
grade 4 or 5 TRAEs. One pt discontinued because of a
TRAE (dizziness).
Conclusions: MK-6482 showed promising efficacy and
tolerability in pts with VHL-associated ccRCC and responses
in other VHL-related lesions. These data support
further investigation of MK-6482 in VHL disease. Clinical
trial information: NCT03401788.
Research Funding: Merck Sharp & Dohme Corp., a subsidiary
of Merck & Co., Inc., Kenilworth, NJ, USA
n Abstract 5006: Phase II study of nivolumab and
salvage nivolumab + ipilimumab in treatment-naïve
patients (pts) with advanced renal cell carcinoma
(RCC) (HCRN GU16-260). Michael B. Atkins, Opeyemi
Jegede, Naomi B. Haas et al.
Results: 123 pts with clear cell(cc) RCC were enrolled between
5/2017 and 12/2019 at 12 participating HCRN
sites. Median age 65 (range 32-86 years); 72% male.
IMDC favorable 30 (25%), intermediate 79 (65%) and
poor risk 12 (10%). 22 (18%) had a component of sarcomatoid
histology (SARC). 117 pts are currently evaluable
for response. RECIST defined ORR was: 34 (29.3%)CR 5
(4.3%), PR 29 (24.8%), SD 47 (40.2%), PD 36 (30.7%).
ORR by irRECIST was 35%. ORR by IMDC was: favorable
12/29 (41.4%), interme-diate/poor 22/87 (25.3%) and for
SARC 6/22 (27.3%). Median DOR is 13.8 (10.9, NA) mo.
Median PFS is 7.4 (5.5, 10.9) mo. 110 pts remain alive.
60 pts (54 PD, 6 pSD) to date were potentially eligible
for salvage nivo/ipi (Part B), but 28 did not enroll due to
symptomatic PD (17), grade 3-4 toxicity on nivo (8),
other (3). 27 of 32 Part B pts are currently evaluable for
efficacy and 30 for toxicity. Best response to nivo/ipi was
PR (11%), SD (30%), PD (59%). ORR by irRECIST was
19%. Grade 3-5 Treatment-related AEs (TrAE) were seen
in 35/123 (28)% on nivo with 1 death due to respiratory
failure. Grade 3-4 TrAE were seen in 10/30 (33%) on
nivo/ipi with 0 deaths. Correlative studies are pending.
Conclusions: Nivo monotherapy is active in treatment
naïve ccRCC across all IMDC groups. Toxicity is consistent
with prior nivo studies. Salvage treatment with
nivo/ipi after nivo monotherapy was feasible in 53% of
pts with PD/pSD, with 11% responding. Clinical trial information:
NCT03117309.
Research Funding: Bristol Meyers Squibb
n Abstract 5007: FRACTION-RCC: Innovative, highthroughput
assessment of nivolumab + ipilimumab
for treatment-refractory advanced renal cell. Toni K.
Choueiri, Harriet M. Kluger, Saby George et al
Results: 46 pts were randomized to NIVO+IPI. Pts had 0
(n = 1), 1 (n = 10), 2 (n = 12), 3 (n = 10), or 4 (n = 13)
prior lines of therapy. All pretreated pts had prior anti-
PD-(L)1-, none had prior anti-CTLA-4- therapy, and 37
had prior TKI-based therapy; 45 pts progressed on anti-
PD-(L)1 as the most recent therapy. Most pts had clear
cell aRCC (n = 44). After a median study follow-up of 8.9
months, ORR was 15.2%; no pts achieved complete response
and 7 achieved partial response. DOR ranged
from 2–19+ months (n = 7); 5 pts had ongoing response.
Six of 7 responders had received 2 prior lines of therapy.
Any-grade treatment-related adverse events (AEs) were
reported in 36 pts (78.3%; fatigue, rash both 19.6%,
and diarrhea 17.4% were most common). Grade 3–4
treatment-related AEs were reported in 13 pts (28.3%; diarrhea
8.7%, amylase and lipase both 6.5% were
most common). Treatment-related immune-mediated
AEs of any grade were reported in 22 pts (47.8%; rash
19.6%, diarrhea 17.4%, and alanine aminotransferase
8.7%). No treatment-related deaths were reported. Updated
and expanded results with an additional 3 months
of follow-up will be presented.
Conclusions: These results suggest that NIVO+IPI may
provide durable partial response in some pts with prior
progression on checkpoint inhibitors, including some
heavily pretreated pts. The safety profile of NIVO+IPI in
FRACTION pts was similar to historic data in aRCC with
this combination. Clinical trial information: NCT0299
6110.
Research Funding: Bristol-Myers Squibb
n Abstract 5008: Phase II trial of lenvatinib (LEN)
plus pembrolizumab (PEMBRO) for disease
progression after PD-1/PD-L1 immune checkpoint
inhibitor (ICI) in metastatic clear cell renal cell
carcinoma (mccRCC). Chung-Han Lee, Amishi Yogesh
Shah, James J Hsieh et al.
Results: 104 pts were enrolled. At data cutoff (January
12, 2020), 71 (69%) pts were still on study treatment.
Most pts had 2 prior anticancer regimens (58%). 91 of
104 pts were evaluable for response at Week 12 (13 pts
NE at Week 12); 46 of 91 pts achieved a confirmed partial
response for an ORR of 51% (Table). Median progressionfree
survival (PFS) was 11.7 months and median duration
of response (DOR) was 9.9 months. The most common
treatment-related adverse events (TRAEs) were fatigue
(49%), diarrhea (44%), proteinuria (37%), hypertension
(31%), nausea (31%), dysphonia (29%), stomatitis (29%),
and arthralgia (27%). There was 1 grade 5 TRAE (upper
gastrointestinal hemorrhage). 43% of pts required dose
reduction and 12% of pts discontinued treatment due to
TRAEs. Response and safety data will be updated to include
all pts evaluable at an April 9, 2020 cut-off.
Kidney Cancer Journal 39