19 / 32
SL-401 demonstrates robust activity
against blastic plasmacytoid dendritic
cell neoplasm
SL-401 has demonstrated
robust single-agent activity in
blastic plasmacytoid dendritic
cell neoplasm (BPDCN),
including a 100% objective
response rate in first-line, and
87% in all lines.
N
aveen Pemmaraju, MD, of the
University of Texas MD Anderson
Cancer Center, Houston, explained
that SL-401 is a novel targeted therapy
directed to the interleukin-3 receptor. The
interleukin-3 receptor is overexpressed
by many haematologic cancers, including
BPDCN, acute myeloid leukaemia,
myeloproliferative neoplasms, and multiple
myeloma.
In a prior phase 1/2 trial, SL-401 demonstrated
clinical activity, including multiple complete
responses, in patients with BPDCN, a highly
aggressive malignancy of unmet medical
need and poor prognosis. Dr Pemmaraju and
colleagues built on this prior experience and
reported updated efficacy and safety data
from their ongoing SL- 401 registration trial
in BPDCN.
This phase 2 trial is a single-arm, open-label,
two-stage study consisting of a lead-in dose
escalation (stage 1) and subsequent expansion
stage (stage 2) designed to generate safety and
efficacy data to support potential registration
in BPDCN.
In stage 1, patients with BPDCN or relapsed/
refractory acute myeloid leukaemia receive
SL-401 as a daily intravenous infusion for up
to 5 days (7, 9, 12, or 16 μg/kg daily) every
21 days.
In stage 2, patients with BPDCN receive SL-
401 at the optimal stage 1 dose and schedule.
Response criteria include skin assessment by
modified severity weighted assessment tool,
and bone marrow, lymph node, and viscera
by standard measures. Clinical complete
response is defined as no detectable disease
in bone marrow, lymph nodes, or viscera, with
microscopic-only skin disease.
At data cutoff (1/20/16), 48 patients
(18 BPDCN; 30 relapsed/refractory acute
myeloid leukemia) were treated with SL-401.
Eighteen BPDCN patients (9+ 9 in stages
1 and 2) received SL-401 (7 μg/kg, n=3
[stage 1]; 12 μg/kg, n=15 [6 + 9 in stages 1
and 2]). The median age was 70 years (range
45–82 and one compassionate use patient
age 15 years).
Data on 30 relapsed/refractory patients with
acute myeloid leukaemia (14+16 in stages
1 and 2) will be reported separately. Most
common treatment-related adverse events
(all grades) were transient transaminase
elevation (57%) and hypoalbuminemia (40%).
Transient thrombocytopenia was also noted
(15%).
Two stage 1 patients had capillary leak
syndrome grade 5 (7 μg/kg) and grade 4 (12
μg/kg). Safety precautions were developed
and successfully implemented to minimise
risk of severe capillary leak syndrome. Since
adoption, severe capillary leak syndrome has
not been observed at doses up to 12 μg/kg. No
cumulative side effects were observed over
multiple cycles.
In stage 1, 12 μg/kg was the maximum tested
and recommended stage 2 dose for BPDCN
and maximum tolerated in relapsed/refractory
acute myeloid leukaemia. Maximum tolerated
dose was not reached in BPDCN. An 87%
(13/15) overall response rate was observed in
15 evaluable BPDCN patients, with marked
disease reductions in skin, bone marrow,
lymph node, and viscera.
A 100% (10/10) objective response rate was
observed in evaluable first-line BPDCN
patients, with 90% (9/10) of patients
achieving complete response (n=7) or
clinical complete response (n=2). A 100%
(8/8) objective response rate was observed in
evaluable first-line BPDCN patients treated
at the optimal dose (12 μg/kg), and all eight
patients achieved either complete response
(n=6) or clinical complete response (n=2).
Six of the eight patients either remain on
SL-401 in complete response (n=4; duration
ongoing at 3+ to 8+ cycles) or were bridged
to stem cell transplant (n=2; one complete
response, one clinical complete response
after seven and four cycles, respectively).
Dr Pemmaraju concluded that SL-401
demonstrated robust single-agent activity in
BPDCN, including 100% objective response
rate in first-line, and 87% in all lines, with
multiple complete responses in a phase 2
trial. Response duration data are maturing
and encouraging.
SL-401 is also being developed in additional
interleukin-3 receptor/ CD123-positive
haematologic malignancies, including acute
myeloid leukaemia in complete response
with minimal residual disease and high-risk
myeloproliferative neoplasms.
EHA 2016
19
DECEMBER 2016