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patients associated with better clinical outcomes
· Immune activation data provides clear scientific rationale for anti-PD1/L1
checkpoint inhibitor combination in upcoming trial in first line mesothelioma
Oslo, Norway, 22 June 2020 - Targovax ASA (OSE: TRVX), a clinical stage immuno
-oncology company developing oncolytic viruses to target hard-to-treat solid
tumors, today releases 12-month efficacy and immunological data from the
randomized phase I/II trial of ONCOS-102 in combination with standard of care
chemotherapy in malignant pleural mesothelioma (MPM).
The trial is an open label, exploratory phase I/II trial adding ONCOS-102 to
standard of care (SoC) chemotherapy (pemetrexed/cisplatin) in first and second
(and later) line MPM to assess safety, immune activation and clinical efficacy
vs SoC only. In total, 31 patients have been treated in the trial, with 20
patients in the experimental group receiving the ONCOS-102 and SoC combination,
and 11 patients in a control group receiving SoC only. The 31 patients have now
completed the 12-month follow-up. The first set of data was reported in January
2020, see press release here (https://www.targovax.com/en/targovax-announces
-encouraging-data-in-mesothelioma-study-combining-oncos-102-and-standard-of-care
-chemotherapy/), with an update in May 2020, see press release
here (https://www.targovax.com/en/targovax-releases-update-for-mesothelioma
-trial-combining-oncos-102-and-chemotherapy/).
The median Progression Free Survival (mPFS) for ONCOS-102 treated first line
patients remains at 8.9 months, which is identical to the previously reported
early data. mPFS for the control group first line patients treated with SoC
chemotherapy only is 7.6 months. The first line mPFS data continues to compare
favorably to SoC historical controls, which have shown mPFS of 5.7-7.3
months[1] (http://#_ftn1). As there is now longer follow-up and few censored
patients left in the PFS analysis, the updated figures can be considered close
to final.
The 12-month survival rate was 64% in the first line ONCOS-102 treated patients,
compared to 50% in the first line control group treated with SoC chemotherapy
only (median Overall Survival is too early to report). The patients continue to
be followed and updated Overall Survival (OS) figures will be published as they
mature. This 64% 12-month survival rate is encouraging compared to the control
group, but there are few historical control reference points. Recently, at ASCO
2020, results from a first line mesothelioma trial assessing SoC chemotherapy in
combination with the anti-PD-L1 checkpoint inhibitor durvalumab showed a 70% 12
-month survival rate. This suggests that ONCOS-102 alone plus SoC chemotherapy
may already achieve a level of benefit close to that observed with checkpoint
inhibition plus SoC chemotherapy. It is expected that addition of checkpoint
inhibition to ONCOS-102 and Soc will provide even further clinical benefit due
to engagement of distinct and complementary biological mechanisms. As such,
Targovax’s future clinical development of ONCOS-102 will focus on first line
mesothelioma with the triple combination of a checkpoint inhibitor, ONCOS-102
and SoC. A randomized phase II trial is currently being planned in collaboration
with a pharma partner.
Tumor biopsy immunohistochemistry and gene expression analyses from the present
trial confirm the predicted mode of action of ONCOS-102. Importantly, profound
innate and adaptive immune activation is observed in the ONCOS-102 treated
patients compared to the control group, and this immune activation is associated
with better clinical outcome. The immune activation is hallmarked by an increase
in intra-tumoral cytotoxic T-cells and upregulation of adaptive immunity and
cytotoxicity related gene expression, in parallel with polarization from M2 to
M1 macrophage phenotype and upregulation of PD-L1 expression, indicating that
ONCOS-102 is driving a favorable remodeling of the tumor microenvironment. This
powerfully demonstrates the immune activation potential of ONCOS-102 far beyond
what is achieved by chemotherapy alone and suggests that patients may be
effectively sensitized to treatment with an anti-PD1/L1 antagonist, thereby
providing strong scientific rationale for the combination of ONCOS-102 and
checkpoint inhibition in first line mesothelioma.
Dr. Magnus Jäderberg, Chief Medical Officer of Targovax, said: “We are very
pleased to see the encouraging first line PFS data holding up in the 12-month
analysis, with early signs of positive survival outcomes. We are particularly
excited to observe a broad and profound immune activation in the ONCOS-102
treated patients, which confirms the proposed mode of action. ONCOS-102
treatment clearly drives a favorable remodeling of the tumor microenvironment,
and this remodeling is linked to better clinical outcomes. This immune activated
tumor micro-environment provides the key scientific rationale and an ideal
backdrop for combination treatment with a checkpoint inhibitor. These data set
us up perfectly to move forward with a trial combining ONCOS-102 and a
checkpoint inhibitor, which we believe will release the full potential of
immunotherapy in this hard-to-treat patient population”.
For a video presentation of the data, please see links below:
· English version (https://youtu.be/xQgT3NhAK5o) Magnus Jäderberg, Chief
Medical Officer
· Norwegian version (https://youtu.be/-V-TwZ08Eg0) Erik Digman Wiklund, Cheif
Business Officer
[1] Vogelzang 2003, Ceresoli 2006, Zalcman 2015, Tsao 2019, Scagliotti 2019
For further information, please contact:
Renate Birkeli, Investor Relations
Phone: +47 922 61 624
Email: renate.birkeli@targovax.com
Media and IR enquires:
Andreas Tinglum - Corporate Communications (Norway)
Phone: +47 9300 1773
Email: andreas.tinglum@corpcom.no
About Targovax
Activating the patient’s immune system to fight cancer
Targovax (OSE:TRVX) is a clinical stage immuno-oncology company developing
oncolytic viruses to target hard-to-treat solid tumors. Targovax’s lead product
candidate, ONCOS-102, is a genetically modified oncolytic adenovirus, which has
been engineered to selectively infect cancer cells and activate the immune
system to fight the cancer.
ONCOS-102 is currently being tested in mesothelioma, melanoma and peritoneal
malignancies and has already shown promising clinical results both as
monotherapy and in combination with chemotherapy, and a checkpoint inhibitor.
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