Annual Meeting Proceedings Part 1 - American Society of Clinical ...

162s Developmental Therapeutics—Clinical Pharmacology and Immunotherapy
2581 General Poster Session (Board #6F), Mon, 8:00 AM-12:00 PM
A phase II, single arm clinical trial involving an alternative cancer treatment
psorinum therapy in patients with unresectable metastatic colorectal
carcinoma. Presenting Author: Aradeep Chatterjee, Critical Cancer Management
Research Centre and Clinic, Kolkata, India
Background: We prospectively studied the clinical efficacy of an alternative
cancer treatment “psorinum therapy” in treating unresectable metastatic
colorectal carcinoma (UMCRC). Methods: Our study was phase-II, open
level, single arm and single stage. Participants eligibility criteria included
(1) histopathology confirmation of the malignancy (2) metastatic and
unresectable disease status (3) No prior conventional cancer treatments
(4) Karnofsky performance status between 40 – 70%. The primary outcome
measures of the study were (1) to assess the radiological tumor response
rate (using CT scanning procedure and following the RECIST criteria); (2) to
assess how many participants survived at least 1 yr, 2 yrs, 3 yrs, 4 yrs and
finally, after 5 yrs of the study. The secondary outcome measure was to
assess the side effects of the investigational anti- cancer drug (psorinum) if
any. Psorinum (an alcoholic extract of scabies slough and pus cells) was
administered orally at a dose of 0.02ml / kg body weight / day as a single
dose on an empty stomach for a complete course duration of 2 yrs to all the
participants along with allopathic and homeopathic supportive cares.
Results: 105 participants included in the final analysis at the end of the
study. According to the RECIST criteria, complete response occurred in 12
(11.43%) cases and partial response occurred in 38 (36.19%) cases. 76
(72.38%) of them survived at least 1 yr, 58 (55.24%) survived at least 2
yrs, 51 (48.57%) survived at least 3 yrs, 43 (40.95%) survived at least 4
yrs and 37 (35.24%) of them survived at least 5 yrs. These participants
didn’t receive conventional or any other investigational cancer treatments.
Conclusions: The results of the study show clinical efficacy of psorinum
therapy in treating patients with UMCRC. The investigational drug psorinum
is non- toxic. Randomized controlled clinical trial should be conducted
for further investigation of this alternative cancer treatment in
treating unresectable metastatic colorectal carcinoma to integrate it into
the mainstream of oncology treatments.
2583 General Poster Session (Board #6H), Mon, 8:00 AM-12:00 PM
Phase I/II, two-part, open-label, multiple-dose, dose-escalation study of
siltuximab in patients with solid tumors. Presenting Author: Eric Angevin,
Institut de Cancérologie Gustave Roussy, Villejuif, France
Background: Siltuximab (S) is a chimeric mAb with high affinity for soluble
IL-6. This Ph 1/2 study evaluated safety, efficacy and PK of escalating,
multiple IV doses of S from a new cell line in patients (pts) with advanced
refractory solid tumors. Methods: In Ph 1, S was given to 20 pts with
advanced solid tumors at escalating dose levels (2.8 or 5.5 mg/kg q2w or
11 or 15 mg/kg q3w) and to 24 pts with taxane and platinum resistant
ovarian cancer (OVC) or KRAS mutant (KRASmt) tumors at 15 mg/kg q3w.
In Ph 2, 17 OVC pts and 23 KRASmt pts received the Ph 1 selected dose of
15 mg/kg q3w. The Ph 2 primary efficacy endpoint was clinical benefit rate
(CBR: CR � PR � SD of � 6 wk). Results: In Ph 1-2, 84 pts (35 colorectal,
29 OVC, 9 pancreatic, 11 other) pretreated with a median of 4 prior tx
regimens received a median of 3 (range 1, 45) cycles. 1 DLT occurred at
5.5 mg/kg; MTD was not reached. 62% pts had AEs gr � 3 in Ph 1-2, most
common were hepatic function abnormalities (15%), PS deterioration
(12%), fatigue (11%). 10% pts had possibly S-related AEs gr � 3; only
neutropenia (4%) was reported in �1 pt. 42% pts had SAEs, most were
related to underlying disease, 2% were possibly S-related. 18 deaths
occurred on study, 17 due to PD, 1 due to AE. No pt had antibodies to S.
The PK profile was bi-exponential with a t1/2 ranging 15 � 20 d. PK profile
of S from the new Chinese hamster ovary cell line appears similar to the
previous murine Sp2/0 myeloma cell line. CBR in Ph 2 was 5%. ORR by
RECIST was 26% SD in Ph 1, 9% SD in Ph 2. 1 OVC pt had CA 125
response. In Ph 2 the median PFS was ~2moinboth cohorts; the median
OS was 4.2 mo in KRAMSmt and 11 mo in OVC. Hb increased by a max of
�10 g/L in 73% pts given 15 mg/kg in Ph 2, with 94% showing a median
decrease of 68% at d 8 after dose 1 in hepcidin, a regulator of iron
homeostasis. CRP was suppressed in all pts during tx, with median
decrease 93% at 11 mg/kg and 88 � 93% at 15 mg/kg as early as d 8 after
dose 1. Other biomarkers will be presented. Conclusions: S appears to be
well tolerated; doses of 11 � 15 mg/kg q3-4w can be used in future
studies. No CR/PR was observed, although some pts with advanced solid
tumors had durable SD and CRP suppression. Improvement in Hb was
observed in a large proportion of pts, indicating a role of IL-6 in anemia that
needs to be further explored.
2582 General Poster Session (Board #6G), Mon, 8:00 AM-12:00 PM
Randomized phase II trial of multipeptide vaccination with or without a
single pre-vaccine dose of denileukin diftitox in advanced melanoma.
Presenting Author: Thomas Gajewski, The University of Chicago, Chicago,
IL
Background: The efficacy of immunotherapy approaches such as vaccines
in melanoma appears limited, in part, due to immune suppressive mechanisms
in the tumor microenvironment. One of these mechanisms is the
presence of CD4�CD25�FoxP3� regulatory T cells (Tregs). It has been
hypothesized that strategies to reduce Treg numbers should improve the
efficacy of melanoma vaccines. Methods: The study design was to randomize
24 HLA-A2� patients to receive vaccine alone or denileukin diftitox (18
mcg/kg i.v.) as a single dose 4 days prior to the first vaccination. The
vaccine formulation consisted of 4 melanoma antigen peptides (derived
from MelanA, gp100, MAGE3, and NA17A) emulsified in Montanide and
GM-CSF, administered i.d./s.c. every 2 weeks. The primary endpoints were
assessment of depletion of Tregs from the peripheral blood, and measurement
of antigen-specific CD8� T cell responses by ELISPOT. Secondary
endpoints included clinical response and analyses of the tumor microenvironment
for changes in Treg infiltration. Results: The treatment was well
tolerated. Enrollment was halted at 16 patients when it was clear that
immune response endpoints would not be reached. There was no significant
decrease in Treg numbers, nor was there an increase in vaccineinduced
T cell responses, when patients received denileukin diftitox prior
to vaccination. In patients with biopsiable tumors, there was no decrease in
Tregs in metastatic lesions post-versus-pre-treatment. Of the 9 patients
who showed clinical benefit (1 PR, 8 SD), 4 of them received denileukin
diftitox and 5 did not. Estimated time to progression was 146 days in the
group that received denileukin diftitox and 131 days in the group that did
not. Conclusions: Denileukin diftitox given as a single dose prior to
vaccination was not sufficient to deplete Tregs or improve the potency of
this melanoma vaccine. Alternative strategies to reduce Tregs, such as
multiple doses of denileukin diftitox or anti-CD25 mAbs, should be
considered.
2584 General Poster Session (Board #7A), Mon, 8:00 AM-12:00 PM
Association of humoral antitumor response with clinical benefit in catumaxomab-treated
malignant ascites patients: Results from a phase IIIb study.
Presenting Author: Peter Ruf, TRION Research GmbH, Martinsried, Germany
Background: The bispecific antibody catumaxomab (anti-EpCAM x anti-
CD3) which is approved for the treatment of malignant ascites (MA)
patients (pts) in the EU elicits a humoral immune response against
tumor-associated antigens. Here we present follow up data analyzing the
influence of this antibody response on puncture free (PFS) and overall
survival (OS). Methods: In the course of the phase IIIb study CASIMAS, MA
pts with EpCAM positive tumors were treated with/without prednisolone
premedication by 4 infusions of 10, 20, 50 and 150 �g of catumaxomab
over 11 days (d). EpCAM and HER2-specific antibody responses in plasma
samples of 23 pts were measured by ELISA. Additionally, samples of 5 pts
receiving a second treatment cycle were analyzed. Pts with significant
increase (� 2) or de novo development of anti-tumor antibodies within 38 d
after treatment start were defined as responders (R). Non responders (NR)
showed no humoral response by d 38 or died before. PFS and OS of R and
NR were compared by Kaplan Meier analysis. Results: 11 of 23 pts (48%)
showed an anti-EpCAM response and 14 of 23 pts (61%) developed
HER2-specific antibodies. 6 pts (26%) reacted positive against both
antigens, 4 pts (17%) had neither response. In contrast to the EpCAM R
group where 73% of pts displayed detectable antibodies prior to therapy,
antibodies against HER2 developed de novo. Of note, 4 of 5 individuals
who received a second treatment cycle after recurring MA demonstrated an
anti-HER2 Ig booster reaction which was stronger and faster in comparison
to pts who received only one treatment cycle (median values at d 18: 65 vs.
11 ng/ml). Most important, there was an almost 6 fold increase in median
PFS between the HER2 R and NR group (68 vs 12 d, p � 0.044 (log-rank).
There was also a trend towards improved OS for pts showing either
anti-HER2 and/or anti-EpCAM responses (n�19) in comparison to pts with
no response at all (n�4; 143 vs. 67 d, median, p � 0.054). Conclusions:
The results indicate that active anti-tumor immunization triggered by
catumaxomab treatment in MA pts is associated with improved clinical
outcome. Further investigations of these vaccine-like effects with higher
pts numbers are warranted.
Visit abstract.asco.org and search by abstract for the full list of abstract authors and their disclosure information.