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ONCOS-102, an oncolytic virus, with pembrolizumab: remodeling of the tumor micro-environment and clinical outcomes in anti-PD1-resistant advanced melanoma
Thomas Hansen
VP
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Pilot study shows safety, benefit against PD-1-resistant melanoma
A pilot study showed that ONCOS-102, an engineered adenovirus immune stimulant directly injected into cancer cells, plus pembrolizumab (Keytruda®), benefited some patients with melanoma resistant to PD-1 immune checkpoint inhibitors. Led by MSK medical oncologist Alexander Shoushtari, the 21-patient trial to establish safety found the combination treatment was generally well tolerated and showed clinical benefit — including the shrinking or disappearance of tumors in 7 of 20 patients. Additionally, 8 of 15 patients also saw some degree of shrinkage in visible but non-injected tumors. The findings support further investigation in a larger population of patients with longer follow-up, the authors write.
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https://newsweb.oslobors.no/message/573458
The ONCOS-102 phase 1b melanoma study is published in the prestigious scientific journal Clinical Cancer Research
· ONCOS-102 in combination with PD-1 checkpoint inhibitor (CPI) Keytruda
demonstrated strong ORR of 35% in PD-1 CPI resistant melanoma, correlating with
robust and persistent immune activation
· A phase 2 trial is under planning, where ONCOS-102 will be tested in a
triple-combination with both PD-1 and CTLA-4 CPIs
Oslo, Norway, 20 October 2022 - Targovax ASA (OSE: TRVX), a clinical-stage
immuno-oncology company developing immune activators to target solid tumors,
today announces that the completed ONCOS-102 phase 1b study in PD-1 CPI
resistant advanced melanoma has been published in the prestigious oncology
journal Clinical Cancer Research, published by the American Association for
Cancer Research (AACR).
PD-1 CPI resistant advanced melanoma is a major unmet medical need affecting up
to 25,000 patients per year in the major markets. The diagnosis is associated
with a poor prognosis and there are currently no approved treatment options
available.
In this phase 1b trial, ONCOS-102 was given intra-tumorally to 21 PD-1 CPI
resistant melanoma patients, followed by re-treatment with the PD-1 CPI
Keytruda. It is anticipated that local injection of ONCOS-102 will induce an
inflammatory immune response in the tumor microenvironment and drive systemic T
-cell activation, which in turn can re-sensitize the patient to PD-1 CPI
therapy.
As expected, ONCOS-102 generated strong and durable immune activation in the
treated patients, which translated into a promising objective response rate
(ORR) of 35%. Importantly, the clinical efficacy was associated with continuous
replication of ONCOS-102 within the tumor, statistically significant increase in
T-cell infiltration, and broad and persistent upregulation of immunological
pathways in responding patients.
Dr. Alexander Shoushtari, Memorial Sloan Kettering Cancer Center, New York said:
“Checkpoint inhibitors have had a significant impact on the way we treat
melanoma; however, a subset of patients still does not respond or become
resistant to treatment. Therefore, there is a high medical need for immune
activating agents to overcome resistance to checkpoint blockade. Although this
was a small study, the 35% ORR and substantial activity in non-injected lesions
is promising, particularly as there is a clear correlation with immunological
biomarker data. We look forward to continuing to work with Targovax in the
upcoming phase 2 trial, which will allow us to validate these findings in a
larger patient cohort as well as to test ONCOS-102 in interesting new
combinations.”
Dr. Lone Ottesen, Chief Medical Officer of Targovax ASA, said: “We are very
happy that our strong ONCOS-102 results in melanoma have been acknowledged by
publication in a high-impact scientific journal. For Targovax, this data set
provides an important clinical proof-of-concept and the translational analyses
have validated and deepened our understanding of the ONCOS-102 mechanism of
action. These findings have allowed us to design a robust phase 2 trial, which
will include combination with the second-generation Fc-enhanced CTLA-4 CPI
botensilimab. CTLA-4 was strongly up-regulated in response to ONCOS-102
treatment in the phase 1b study, and we believe this combination has the
potential to boost response rates up and above 35%, and thereby establish ONCOS
-102 as a leading product candidate in PD-1 resistant melanoma.”
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Upcoming phase 2 trial… Med samme tilnærming som i melanom??
Siden det er sagt at melanom er siste Targovax sponsede studie, er det å forvente at andre tar kosten her??
Det hadde vært en kursdrivende melding.
Imponerende av Targo-toget. Innta plassene. Klar for avgang.
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Er det noen kloke hoder her som kan si litt om hva som er nytt siden sist.
**The ONCOS-102 phase 1b melanoma study is published in the prestigious scientific journal Clinical Cancer Research *.
" with updated publication info"
Polygon og Boblegutten kan sikkert bidra om de har tid og mulighet?
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Dette ble lagt til i den oppdaterte meldingen.
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Fra artikkelen: "Reduction in the size of non-injected targeted lesions was seen in more
than half (53%) of evaluable patients, including six with ≥ 30% relative
reduction in tumor size, corresponding to PR per response criteria for
intratumoral immunotherapy (itRECIST; ref. 36).
Halvparten av pasientene fikk altså redusert tumor-størrelse i tumorer som ikke var blitt direkte injisert med Oncos-102. Det betyr altså en systemisk, tumor-spesifikk immunrespons, som igjen er i direkte samsvar med et positivt forløp for pasienten.
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Også viktig å huske hvor frustrert Dr. Alexander Shoushtari var over at protokollen forhindret han fra å injesere flere doser…
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Kursmessig så får vi neppe et stort løft før det kommer noe som lukter cash, eller volumet intradag tar knekken på denne daglige byttinga av aksjer som har pågått siden primo/medio august. Eller kanskje enda lenger tilbake i tid. Blir jo uvel av å se på dette dag ut og dag inn.
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Forfatterne av artikkelen viser til at det er bedre effekt i del 2 av studien, der det er flere injeksjoner av oncos. Anbefalingen der er altså å basere seg på del 2 samt muligens også øke dosering pr injeksjon, for å booste effekten ytterligere.
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Forøvrig, børsmleding nr 2 i morges:
These findings have allowed us to design a robust phase 2 trial, which
will include combination with the second-generation Fc-enhanced CTLA-4 CPI
botensilimab. CTLA-4 was strongly up-regulated in response to ONCOS-102
treatment in the phase 1b study, and we believe this combination has the
potential to boost response rates up and above 35%, and thereby establish ONCOS
-102 as a leading product candidate in PD-1 resistant melanoma.
Som jeg påpekte her om dagen, så viser dataene at Oncos-102 reaktiverer uttrykket av CTLA-4 i mye større grad enn PD-L1. PD-L1 er mål for pembrolizumab/Keytruda og er typen CPI brukt i denne studien.
Reaktivering og høyt uttrykk av CTLA-4 vil i teorien bety at en CPI mot denne vil fungere bedre enn Keytruda. Og når vi hører lovordene og forventningene til botensilimab som skal brukes i fase 2 studien i denne indikasjonen, så er det lov å skru opp forventningene. Botensilimab er en 2. generasjon CPI mot CTLA-4, og den er designet slik at det kun brukes monoklonale antistoffer (altså CPI) som aktiverer immunforsvaret mot tumor. Keytruda og de andre CPI`ene på markedet er av typen 1. generasjon, der antistoffene både aktiverer og nedregulerer immunresponsen mot tumor.
Å si at mine forventninger til Fase 2 studien er “relativt optimistiske” er pr deff en underdrivelse…
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Takk for bidraget 
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Fantastiske nyheter.
Har vi truffet innerblink denne gangen?
Neste , BP samarbeide eller oppkjøp?
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Det drysses godmeldinger hele tiden. Dette må gå hele veien nå, hvis ikke skjønner jeg ingenting.
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Markedet reagerer med et gjesp
Ingen inside kjøp og det er nok en grunn. Er de i forhandlinger om oppkjøp? Mine antagelser 
Uansett meget spennende tider for TARGOVAX nå 
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