Saken er at vi har lett- og leter kontinuerlig etter data som evt. viser at CPI i relevant indikasjon har fungert bedre i helt nyeste tid. Vi har ikke funnet det enda. Tvert imot. Om noen skulle finne det vil det bli delt sporenstreks. Sånn det skal og bør være. INITIUM er langt på overtid, våre forsøk på antiteser feiler (heldigvis).
Hur ser ni på sannolikheten att vi får se en nyemission, inte minst med tanke på att resultaten från Initium-studien förväntas dröja?
At det er ikke så relevant å diskutere emisjon før det foreligger mer informasjon om NIPU og INI. Det er ikke pressende for selskapet, og hvordan en emisjon utspiller seg avhenger helt og holdent på ny informasjon som kommer ila året
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Det har vært en del fram og tilbake med tolkninger av hva som står på ESMO sine sider og hva selskapet har kommunisert om når vi evt. får beskjed om aksept av presentasjon av NIPU som en LBA. Jeg har fått bekreftet hvordan ting henger sammen fra IR nå med følgende sitat fra ESMO:
«you don’t have to wait until the 19th, but you cannot issue it as soon as you receive the notification. You have to wait until titles are published on the ESMO web site, which normally happen around one week after the notification.»
Deltakerene får altså beskjed innen slutten av denne måneden. Det betyr at en melding kan komme helt fra omtrent nå til en ukes tid ut i oktober. 2. oktober er altså ikke et endelig «moment of truth» slik de fleste av oss har trodd.
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Initium studien får naturlig nok ikke så mye fokus i diskusjonene her inne nå når alle har blikket rettet mot NIPU og ESMO i oktober. Tar en liten generell oppsummering for evt nye brukere.
Initium er langt på overtid.
Avlesning etter oppnådde 70 events har ikke skjedd da 70 ikke hadde inntruffet pr. 21. August og med stipulert avlesning i H1 2024 er det usikkert når og om dette vil inntreffe innen fornuftig tidsramme.
Gjennomsnittlig oppfølgning nå er ca 22, 5 mnd. Siste pasient ble innrullert i juni 2022 dvs for ca 15 måneder siden.
Når vi vet følgende:
- CM67 kontrollstudien har en mPFS på 11,5 mnd.(11,7)
- I senere samlingbare studier under covid parallelt med Initium har mPFS vært kortere enn CM67.
- Studier gjennomført under covid har ikke resultert i større frafall, jfr innlegg her på tråden 1957 fra Polygon.
Det begynner å bli svært små teoretiske muligheter nå for at UV1 i Initium ikke skal levere sensasjonelle signifikante resultater.
Sannsynlighetskurven til Kjetilaaj ser slik ut - husk bare å flytte den grønne loddrette streken til dagens dato 20. September 2023. Kanskje Kjetilaaj vil ajourføre dette til eventuelle nye TI brukere som har kommet inn etter NRK reklamen.
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Kan jo oppdatere listen med publikasjoner, siden det kom til et nytt tilskudd for noen uker siden:
April 2017
Immune responses against UV1 peptides were confirmed in 18/21 evaluable patients (85.7%), PSA declined to <0.5 ng/mL in 14 (64%) patients and in ten patients (45%) no evidence of persisting tumour was seen on MRI in the prostatic gland. At the end of the nine-month reporting period for the study, 17 patients had clinically stable disease.
Treatment with UV1 and GM-CSF gave few adverse events and induced specific immune responses in a large proportion of patients unselected for HLA type. The intermediate dose of 0.3 mg UV1 resulted in the highest proportion of, and most rapid UV1-specific immune responses with an acceptable safety profile. These results warrant further clinical studies in mPC.
November 2020
Treatment with UV1 was well tolerated with no serious adverse events observed. Seventeen patients were evaluable for tumor response; 15 patients had stable disease as best response. The median progression free survival (PFS) was 10.7 months, and the median overall survival (OS) was 28.2 months. The OS at 4 years was 39% (7/18). Five patients are alive (median survival 5.6 years), and none of these are known to have received checkpoint therapy after vaccination. UV1 induced specific T-cell responses in the majority (67%) of patients. Immune responses were dynamic and long lasting. Both immune response (IR) and OS were dose related. More patients in the highest UV1 dosage group (700 μg) developed IRs compared to the other groups, and the IRs were stronger and occurred earlier. Patients in this group had a 4-year OS of 83%. The safety and clinical outcome data favor 700 μg as the preferred UV1 dose in this patient population. These results provide a rationale for further clinical studies in NSCLC with UV1 vaccination in combination with immune checkpoint blockade.
Mai 2021
Background: Ipilimumab improves survival for patients with metastatic malignant melanoma. Combining a therapeutic cancer vaccine with ipilimumab may increase efficacy by providing enhanced anti-tumor immune responses. UV1 consists of three synthetic…
Twelve patients were recruited. Adverse events were mainly diarrhea, injection site reaction, pruritus, rash, nausea and fatigue. Ten patients showed a Th1 immune response to UV1 peptides, occurring early and after few vaccinations. Three patients obtained a partial response and one patient a complete response. Overall survival was 50% at 5 years. Treatment was well tolerated. The rapid expansion of UV1-specific Th1 cells in the majority of patients indicates synergy between UV1 vaccine and CTLA-4 blockade. This may have translated into clinical benefit, encouraging the combination of UV1 vaccination with standard of care treatment regimes containing ipilimumab/CTLA-4 blocking antibodies.
Mai 2021
Background Malignant pleural mesothelioma (MPM) is a rare and aggressive tumour. For patients with inoperable disease, few treatment options are available after first line chemotherapy. The combination of ipilimumab and nivolumab has recently shown…
Across the three phase I/II-studies conducted with UV1, vaccine-specific immune responses were observed in 78% (range 67–91%) of patients across the different cancer types (and HLA allele types), supporting the universality of the vaccine. Survival time for patients who responded immunologically was longer than for patients who did not respond immunologically to the vaccine, and survival time correlated with the breadth of the vaccine-specific immune response […] In summary, UV1 is safe alone and in combination with checkpoint inhibitors and trials in other cancers show that UV1 induces vaccine-specific immune response associated with survival.
Juli 2021
Telomerase-based therapeutic cancer vaccines (TCVs) have been under clinical investigation for the past two decades. Despite past failures, TCVs have gained renewed enthusiasm for their potential to improve the efficacy of checkpoint inhibition…
Telomerase as a TCV target has apparent advantages due to its universal presence and essential function in almost all cancer types, providing spatiotemporal relevance to the induced immune response and limiting possible escape mechanisms for the tumor.
[…]
Immunologically rational combinations, such as anti-CTLA-4 and anti-PD-1/L1, are likely necessary to bring out the true clinical potential of hTERT-targeting TCVs. There are already several phase II randomized controlled trials evaluating hTERT targeting TCVs in combination with CPIs with anticipated read-outs.
Mai 2022
Background: Therapeutic cancer vaccines represent a promising approach to improve clinical outcomes with immune checkpoint inhibition. UV1 is a second generation telomerase-targeting therapeutic cancer vaccine being investigated across multiple…
In total, 78.4% of treated patients mounted a measurable vaccine-induced T cell response in blood. The immune responses in the malignant melanoma trial, where UV1 was combined with ipilimumab, occurred more rapidly and frequently than in the lung and prostate cancer trials. In several patients, immune responses peaked years after their last vaccination. An in-depth characterization of the immune responses revealed polyfunctional CD4+ T cells producing interferon-γ and tumor necrosis factor-α on interaction with their antigen. Long-term immunomonitoring of patients showed highly dynamic and persistent telomerase peptide-specific immune responses lasting up to 7.5 years after the initial vaccination, suggesting a plausible functional role of these T cells in long-term survivors. The superior immune response kinetics observed in the melanoma study substantiate the rationale for future combinatorial treatment strategies with UV1 vaccination and checkpoint inhibition for rapid and frequent induction of anti-telomerase immune responses in patients with cancer.
September 2022
Background: This clinical trial evaluated a novel telomerase-targeting therapeutic cancer vaccine, UV1, in combination with ipilimumab, in patients with metastatic melanoma. Translational research was conducted on patient-derived blood and tissue…
Vaccine-specific immune-responses were detected in 91% of evaluable patients. Clinical responses were observed in four patients. The mPFS was 6.7 months, and the mOS was 66.3 months. There was no association between baseline tumor mutational burden, neoantigen load, IFN-γ gene signature, tumor-infiltrating lymphocytes, and response to therapy. Tumor telomerase expression was confirmed in all available biopsies. Vaccine-enriched TCR clones were detected in blood and biopsy, and an increase in the tumor IFN-γ gene signature was detected in clinically responding patients. Clinical responses were observed irrespective of established predictive biomarkers for checkpoint inhibitor efficacy, indicating an added benefit of the vaccine-induced T cells. The clinical and immunological read-out warrants further investigation of UV1 in combination with checkpoint inhibitors.
Januar 2023
Key points
- The clinical efficacy of checkpoint inhibitors depends on preexisting, spontaneous immune responses against patients’ tumors.
- Anti-hTERT immune responses appear beneficial for melanoma patients, and telomerase represents an attractive target for vaccination.
- Cancer vaccines represent an independent mode of action capable of increasing cancer patient repertoire of tumor specific T cells.
- Survival data are expected imminently from INITIUM, a randomized phase II clinical trial ( n = 156) in metastatic melanoma comparing the effects of treatment with the standard-of-care checkpoint inhibitors, ipilimumab and nivolumab, with and without the telomerase vaccine, UV1.
In the near future, randomized data from clinical trials involving therapeutic cancer vaccines and checkpoint inhibitors will be available. Positive readout may spark broad development and allow cancer vaccines to find their place in the clinic as an important component in multiple future CPI combinations.
August 2023
Cancer vaccines represent a novel treatment modality with a complementary mode of action addressing a crucial bottleneck for checkpoint inhibitor (CPI) efficacy. CPIs are expected to release brakes in T-cell responses elicited by vaccination, leading to more robust immune responses. Increased antitumor T-cell responses may confer increased antitumor activity in patients with less immunogenic tumors, a subgroup expected to achieve reduced benefit from CPIs alone. In this trial, a telomerase-based vaccine was combined with pembrolizumab to assess the safety and clinical activity in patients with melanoma.
Results: The combination was considered safe and well-tolerated. Grade 3 adverse events were observed in 20% of patients, with no grade 4 or 5 adverse events reported. Vaccination-related adverse events were mostly mild injection site reactions. The median PFS was 18.9 months, and the 1- and 2-year OS rates were 86.7% and 73.3%, respectively. The ORR was 56.7%, with 33.3% achieving complete responses. Vaccine-induced immune responses were observed in evaluable patients, and inflammatory changes were detected in posttreatment biopsies.
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Ultimovacs Announces that the Results from UV1 Phase II Clinical Trial NIPU in Malignant Mesothelioma will be Presented at the ESMO Congress 2023
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Legger innlegget til @Inkognito666 her også, så det ikke går tapt for enkelte i småprat.
Med referanse til:
Dersom Helland allerede observerte (betydelig) forbedret progresjonsfri overlevelse (PFS) og tegn til bedre overlevelse ved 69 events når begge armene bruker immunterapi, så er det kanskje grunn til å være litt optimistisk?
Så uttaler CEO ordrett i siste Q-webcast 22/8 at:
When the images were analysed by the radiologists at the study hospitals we clearly met the endpoint on PFS and the difference between the two arms was statistically significant.
Det betyr at de ikke akkurat klarte HR 0.73, men befant seg enda lavere. Så kan man bare spekulere i hva Helland kan si på ESMO om OS.
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Ved 69 events må de da ha hatt minimum 20% bedre OS i UV1 armen for å kunne kalle det klinisk signifikant. Så det blir minimum:
38 events i kontrollarmen og 31 events i UV1 armen eller bedre. Det i seg selv lover godt 
Men har de ikke bare sagt at de ser en lovende trend på OS? Eller noe i den duren?
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Jo, det er riktig at lederen for NIPU-studien, i tilknytning til børsmeldingen den 7. juni, uttalte dette.
Men her må man ikke glømme at børsmeldingen gjaldt resultatet mht det definerte primærendepunktet, mPFS.
Når Helland nå skal presentere NIPU-studien ved ESMO om vel to uker, vil oppmerksomheten i hovedsak være retta mot hva oppdaterte overlevelsesdata viser. Disse vil være flere måneder mer modne.
Skulle trenden i de tidlige overlevelsesdata nå både bekreftes og forsterkes, så står vi i den situasjonen at BICRs konklusjon kan bli “overkjørt” av gullstandardsdata; altså “overall survival”.
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- juni hadde det vel totalt i de to armene vært 69 PFS events, ikke 69 OS events som du antyder her…?
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ESMO presentasjonen hadde vel neppe blitt godkjent om OS ikke er forbedret siden forrige readout?
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Det har vel ikke vært noen «read out» av annet enn den binære vurderingen av PFS nådd eller ikke nådd? Det fantes selvsagt mer data også for OS, men det tidspunktet var jo styrt av PFS og antall events som var oppnådd på det tidspunktet.
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Fra studien står det å lese…Progresjonsfri overlevelse (PFS) i henhold til Modified Response Evaluation Criteria in Solid Tumors (RECIST) som bestemt ved blindet uavhengig sentral gjennomgang (BICR) vurdert ved radiologiske vurderinger
Ferdig snakka. PFS er en gjennomgang av …radiologiske vurderinger
Dette innlegget ble rapportert og er midlertidig skjult.
Hundre prosent korrekt. Men hva mener du med “Ferdig snakka”?
Det vi kan være trygge på, er at Åslaug Helland ikke har sendt abstraktet sitt til ESMO - og fått antatt det for publisering og muntlig presentasjon - som en invitasjon til “omkamp” om konklusjonen til BICR.
Poenget er at “Overall survival” troner høyt over samtlige surrogatendepunkter, herunder også PFS.
Med andre od; om oppdaterte overlevelsesdata allerede nå skulle gi et signifikant resultat, havner BICRs kjennelse langt bak i bakspeilet. Både hos FDA, Bristol Myers Squibb og øvrige farmagiganter (og CPI-eiere) som måtte følge interessert med.
Red.
Om OS-data ennå ikke har nådd signifikant nivå, så kan de ha gjort det ved neste korsveg. For eksempel etter at samtlige pasienter har gjennomgått ett års oppfølging. Da er vi litt utpå nyåret.
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Ultimovacs Receives FDA Orphan Drug Designation for the UV1 Cancer Vaccine for Treatment of Mesothelioma
- The orphan drug designation was granted based on data from the randomized
Phase II clinical trial NIPU
- The results from the NIPU study will be presented at the ESMO Congress being
held October 20-24, 2023 in Madrid- UV1 also received FDA orphan drug designation for treatment of patients with
malignant melanoma in December 2021Oslo, October 09, 2023: Ultimovacs ASA (“Ultimovacs”) (OSE ULTI), a clinical-
stage biotechnology leader in novel immunotherapeutic cancer vaccines, today
announced that the U.S. Food and Drug Administration (FDA) has granted Orphan
Drug Designation (ODD) to the company’s therapeutic cancer vaccine UV1 for the
treatment of patients with mesothelioma. The designation was granted based on
the initial data from the Phase II clinical trial, NIPU.Mesothelioma is a rare and aggressive form of cancer with a high mortality rate
and few therapeutic options. Patients with mesothelioma commonly have a history
of occupationally or environmentally exposure to asbestos, and it typically
takes decades for this specific form of cancer to develop.The impact of UV1 vaccination in patients with malignant pleural mesothelioma is
being assessed in the randomized Phase II clinical trial, NIPU. In the study,
UV1 was combined with checkpoint inhibitors ipilimumab and nivolumab and
compared to ipilimumab and nivolumab alone as a second-line treatment after
first-line treatment with platinum-based chemotherapy. The randomized, open-
label, multicenter trial with 118 patients was conducted in Australia, Denmark,
Norway, Spain, and Sweden. The first patient in the trial was enrolled in June
2020, and the last patient was enrolled in January 2023. The NIPU study is
sponsored by Oslo University Hospital with support from Bristol-Myers Squibb and
Ultimovacs.The results from the study will be shared at the ESMO Congress in Madrid, held
October 20-24, in an oral presentation by the Principal Investigator, Åslaug
Helland, MD, Ph.D., Professor at Oslo University Hospital. The presentation
title is “LBA99 - First survival data from the NIPU trial; A randomized, open-
label, phase II study evaluating nivolumab and ipilimumab combined with UV1
vaccination as second-line treatment in patients with malignant mesothelioma”.“Gaining FDA orphan drug designation for UV1 in mesothelioma highlights UV1’s
potential and the significant need for new treatment options for this patient
population,” said Carlos de Sousa, CEO of Ultimovacs. “We look forward to the
presentation of the NIPU results at the ESMO Congress later this month and to
continue our dialogue with the FDA as we seek to bring UV1 to cancer patients as
quickly as possible.”The FDA’s Office of Orphan Products Developments grants orphan status to support
the development of medicines for rare disorders that affect fewer than 200,000
people in the U.S. Orphan drug designation provides certain benefits, including
potentially up to seven years of market exclusivity upon regulatory approval,
exemption of FDA application fees, and tax credits for qualified clinical
trials.UV1 is a therapeutic cancer vaccine that generates an immune response against
the human telomerase (hTERT) enzyme. The enzyme is essential for the ability of
cancer cells to proliferate. Telomerase is present in 85-90% of all cancers
across all stages of the disease.Ultimovacs is evaluating the universal cancer vaccine UV1 in a broad clinical
development program across various cancer indications with different biologies
and disease stages, combined with different checkpoint inhibitors. The topline
data from NIPU are the first results among the currently five randomized trials
in the UV1 Phase II clinical program. In addition to malignant pleural
mesothelioma, Phase II studies are ongoing in patients with malignant melanoma,
head and neck cancer, ovarian cancer, and non-small cell lung cancer. The
topline data from the malignant melanoma and head and neck cancer trials are
also expected within a year. UV1 is a patented, proprietary technology owned by
Ultimovacs.
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