Immunicum announces INTUVAX phase I/II data at ASCO 2014

ASCO 2014

Immunicum AB, a bio-pharmaceutical company developing therapeutic
cancer vaccines, today announced that phase I/II data has been presented
during a general poster session at the American Society of Clinical Oncology
(ASCO) 2014 annual meeting on the Company’s clinical candidate, INTUVAX, in
patients with metastasized renal cell carcinoma (mRCC).
In addition to demonstrating a favorable safety profile, INTUVAX, as a single agent,
has shown clear signs of tumor specific immune activation and encouraging survival
data for patients with poor prognosis. Furthermore, preliminary data indicate a
synergistic effect between INTUVAX and subsequent treatment with tyrosine kinase
inhibitors (TKIs).
- We are very encouraged by the phase I/II results and the highly positive
feedback we received at the ASCO conference. Although the patient
population is limited, the data we have obtained indicate that INTUVAX
induces a tumor-specific immunity, which appears to inhibit the growth rate of
tumor metastases and thus prolong survival. We are also very happy to see
that preliminary data indicate that subsequent treatment with TKIs may
accentuate the antitumour effect in a synergistic manner. This synergy may
well be due to some TKIs’, particularly sunitinib’s, ability to "open up " the
tumor for vaccine-induced cytotoxic T cells via a well-documented mechanism
that down-regulates the tumor tissue’s immunosuppressive environment, says
Immunicum’s Chief Scientific Officer, Alex Karlsson-Parra.
- - The results just seems to get better and better as data matures. Besides that
we have not yet reached median survival for patients with poor prognosis and
that eight patients are still alive, two patients have for instance, without any
add-on therapy, exhibited a late ongoing clinical response after initial slow
progress. This is consistent with the theory that the immune system may
sometimes need time to build an effective anti-tumor response. We now look
forward to continue to evaluate the clinical efficacy of INTUVAX in a fully
funded phase II study in patients with metastatic renal cell cancer, says
Immunicum’s CEO, Jamal El-Mosleh.
Presentation details are as follows:
All 12 patients were included in the evaluation of immunological and safety
parameters. However, one patient was not included in evaluation of clinical efficacy
as he had 2 concomitant cancers (myeloma and RCC) and not RCC with
metastases.
INTUVAX (5-20 million vaccine cells) was injected intratumorally twice with 2 weeks
interval before nephrectomy.
• The safety profile was excellent. Adverse events with potential relationship to
vaccination mainly consisted of short time fever (5 patients). No clinical or
laboratory signs of autoimmunity were observed in any patient.
• Nine out of 11 evaluated patients exhibited an increased number of tumorspecific
and IFN-gamma producing lymphocytes (ELISPOT-assay including
addition of autologous tumor material) when comparing pre-values with values
obtained 1 week after the second vaccination.
• A massive infiltration of CD8+ T cells was found in 5 out of 12 removed kidney
tumors which, to the best of Immunicum’s knowledge, is the most intensive
and general intratumoral infiltration of CD8+ T cells ever reported in any
human solid tumor. An additional two patients also showed a strong
intratumoral infiltration of CD8+ T cells.
• No initial objective tumor regression (according to so-called RECIST-criteria)
was observed in any patient. However, three of the four patients who have so
far received subsequent therapy with TKIs (3, 4, 9, and 17 months after
vaccination), show an ongoing partial tumor regression. One of these
responding patients (Heng/MSKCC poor prognosis) exhibited an extensive
sarcomatoid transformation of the resected primary tumor. Notably, another
responding patient with MSKCC poor prognosis, and who developed 4 brain
metastases 4 months after INTUVAX treatment, has responded with a
complete disappearance of two lesions and prominent shrinkage (>60 %) of
the other two lesions 6 months after initiation of sunitinib treatment. These two
cases of objective response upon subsequent sunitinib treatment is surprising
since recent data indicate that brain metastases as well as RCC with
extensive sarcomatoid transformation are highly resistant to sunitinib.
• Two patients exhibiting a late ongoing clinical response without add-on
therapy, despite initial slow progress. One patient exhibits an ongoing stable
disease for more than 6 months after previous slow tumor progression for 15
months. Remarkably, yet another patient exhibited an ongoing late objective
partial (>40 %) tumor regression, without add-on therapy with TKIs that started
after 16 months of very slow progression.
• One year survival rate for the whole study group is currently at 63 % (8 of 11
patients up for efficacy evaluation are still alive) which is comparable with
historical data for newly diagnosed poor + intermediate prognosis patients on
sunitinib or sunitinib + autologous DC-based cancer vaccination.
• Median overall survival (mOS) for the whole patient population, or for different
prognosis groups (poor and intermediate), is still not reached but has currently
already surpassed recently reported mOS for newly diagnosed mRCC patients
with MSKCC poor prognosis receiving upfront sunitinib before nephrectomy or
newly diagnosed mRCC patients with Heng poor prognosis receiving an
autologous DC-based cancer vaccine + sunitinib (12.7 vs 9.0 and 13.4 vs 9.1
months, respectively).
• Median OS (from diagnosis) for the patient group with poor prognosis (Heng
criteria) and concomitant extensive sarcomatoid differentiation (n=3, one
received sunitinib 3 months after vaccination) was 7.5 months, which
compares favorably with recent published data on mOS (from diagnosis),
which was 3.0 months in this subgroup with very poor prognosis.
• No clear-cut correlation between the numbers of injected vaccine cells, degree
of HLA-incompatibility between vaccine cells and patient tissue or intratumoral
infiltration of CD8+ T cells and OS has been observed. However in patients
with sarcomatoid differentiation (n=6) a tendency to prolonged survival is
found in those with massive intratumoral infiltration of CD8+ T cells; OS for 2
patients with moderate CD8+ T cell infiltration was 3.8 and 7.5 months
respectively and OS for 4 patients with massive infiltration was 7.0 months for
one patient, while 3 patients are still alive at 10.0, 14.2 and 21 months after
diagnosis.
Conclusions
Immunicum’s findings indicate that intratumoral injection of pre-activated allogeneic
DCs is safe and induces a systemic CTL-mediated anti-tumor response that may
prolong survival in mRCC-patients. Moreover, data on patients who have received
additional treatment with TKIs indicate a synergistic effect between intratumoral
INTUVAX-vaccination and subsequent treatment with TKIs. A fully financed phase IIstudy
is currently in the final phase of planning.
For further information, please contact:
Jamal El-Mosleh, CEO of Immunicum, +4631-415052,
jamal.el-mosleh@immunicum.com
Redeye AB is chosen as the Company’s Certified Adviser.
Tel: +468-545 013 31. www.redeye.se.
About Immunicum AB (publ):
Immunicum AB (publ) develops cancer immunotherapies. Its two main groups of
therapeutic cancer vaccines, SUBCUVAX® and INTUVAX®, and the method of
expansion of tumor-specific T-cells (CD70) is based on the Nobel prize awarded
discovery of the dendritic cell and its central role in the activation of the specific
immune response. Since the raw material consists of allogeneic dendritic cells,
Immunicum’s products can be produced in large scale. The vaccines are now
undergoing clinical trials in renal cell carcinoma and hepatocellular carcinoma.
www.immunicum.com