Ultimovacs (ULTI) Fundamentale forhold

[Birgitte]

Kjetilaaj sin simulering gjort 02.07.23. Kontrollgruppen beregnet etter CM067.

Så kan dere selv flytte den grønne streken til dagens dato.

[h3nk1]

Tenk om noen aktører der ute skjønte hva som var i ferd med å skje her - helt utrolig.

Som om ikke det er nok at vi ikke har funnet studier som har performet bedre med SOC (ipi+nivo) enn CM743, så kan man i tillegg med relativt god grunn anta at kontrollgruppen underperformer (pandemieffekt).

Og kursen er NED på POC i 2L meso. Markedssvikt.

[Hallakis]

@h3nk1

Som om ikke det er nok at vi ikke har funnet studier som har performet bedre med SOC (ipi+nivo) enn CM743, så kan man i tillegg med relativt god grunn anta at kontrollgruppen underperformer (pandemieffekt).

På tross av dette må man samtidig erkjenne at det finnes personer som mener det er legitime grunner til at kontrollarmen i INITIUM overpresterer målt mot CM743.

Det finnes ingen Real-World studier som kan backe opp dette (snarere tvert imot), men uansett ser grafene fortsatt MEGET hyggelig ut, selv med en kontrollgruppe som presterer mye bedre (se bilde under) - merk at prosenter osv er feil da streken kun er tegnet inn i paint, men dere skjønner greien.

[Laaarsas]

Hej kära vänner!

Jag har studerat OS-grafen från NIPU lite mer och experimenterat lite. Jag försöker nedan beskriva min metod, och jag förstår att den säkert kan vara felaktig på många sätt och tar gärna emot kritik. Jag vet att det gjordes ett inlägg här eller i småpratråden med en simulering på hur KM-kurvorna kan komma att se ut i framtiden, men jag hittar inte detta inlägg. Tacksam om det kan delas här igen. Detta är ett inlägg på samma spår.

Metod:
Jag har räknat antal censurerade patienter mellan 7 månader (minimum follow-up time) och den sena korsningen (“selekterade censurerade patienter”), och får då detta (kan vara felräknat):

Experimentarmen: 14 st (A1-14)
Kontrollarmen: 13 st (B1-13)

Jag antar optimistiskt att alla dessa är i livet och kommer fortsätta följas upp.

Jag har sedan kollat vilken procent de står på i KM-kurvan, och sedan utgått från att den mest sannolika platsen på KM-kurvan som de avlider är vid en halvering av överlevnadschansen. T.ex. om en patient är censurerad vid 70% survival probability, så antar jag att denna i genomsnitt (enligt exponentialfördelning(??)) kommer leva till 35% på KM-kurvan. Jag har gjort detta för alla patienter i båda armarna och skapat följande bild:

Om antaganden ovan är godtagbara, ser vi att 3 av de selekterade censurerade patienterna i experimentarmen är förväntade att leva kortare än samtliga i kontrollarmen. 11 kommer leva längre. Detta borde leda till att KM-kurvan för experimentarmen “trycks upp”. Exakt hur KM-kurvan kan komma att se ut vet jag inte. Men om de pat i kontrollarmen som förväntas leva kortast, istället lever längre än ca. 18 månader, så lär den sena korsningen försvinna.

En fråga: Är detta jag försökt “räkna fram” helt onödigt redan inbyggt i nuvarande KM-plot? Nuvarande KM-kurva tar väl hänsyn till hur lång tid censurerade patienter levt?

[skipper]

Dette blir i mine øyne for spekulativt selv om jeg liker tanken din. Dataene må modnes og det vi vet per dags dato er at UV1 armen gjør det bedre enn kontroll og at forskjellen er signifikant. Pasientene med best respons vil vel også få event senere og derved bidra til KM-plottet senere i studien også(?) Så alt dette vil endres med tid😊

[polygon]

@Laaarsas

En fråga: Är detta jag försökt “räkna fram” helt onödigt redan inbyggt i nuvarande KM-plot? Nuvarande KM-kurva tar väl hänsyn till hur lång tid censurerade patienter levt?

Nåværende KM-plot kompenserer for sensurering og gjør trappetrinnene høyere og høyere og får halene på plottet til et nivå som er mest sannsynlig gitt de data man har. Men både fasong og nivå kan fortsatt endre seg ganske betraktelig med så mange sensurerte spredt utover. Du tenker nok helt riktig mht. de pasientene som eventuelt kan endre plottene rundt den sene krysningen. Jeg teller også 14 sensurerte i eksperimentell arm, og 13 sensurerte i kontrollarm etter syv måneder dersom du har satt streken der jeg tror (det er 9 sensurerte mellom 12 og 18 måneder totalt). Men når du kommer til å regne ut når disse pasientene faktisk kan gå bort mister du meg. Da tror jeg dette ender opp med å bli veldig spekulativt. Der tror jeg vi må begrense oss til å si at det absolutt er mulig at vi ender opp med plot som ikke krysser, slik @the1nonly viste så eminent i sitt innlegg som du finner her:

Ultimovacs småprat

Har vært en del diskusjoner rundt KM plottene som vi nå har fått etter presentasjonen fra Helland. Som flere allerede har påpekt så er minste oppfølgingstid rundt 7 mnd. (data cutoff August), og det er ganske mange sensurerte. Disse kan enten være i live i August eller de har trukket seg fra studien. Vi vet ikke hvem som er hva, men vi vet de som er sensurert og i live vil kunne få en event ved senere oppfølging (studien følges opp inntil 5 år). Tenkte å prøve illustrere hva det vil si at data…

[ketilaaj]

@Laaarsas

Jag har studerat OS-grafen från NIPU lite mer och experimenterat lite.

Jeg oppfatter at du prøver å finne ut hvordan KM grafene kan modnes og om kryssingen da forsvinner.

Jeg mener det er en bedre og gir et mer komplett bilde å anta at Cox proportional er gyldig og tilpasse en “best fit” til hver av armene. Da vil du vekte inn alle dataene i KM kurven, ikke bare de du har plukket ut her.

Hvis du så plotter beggge kurvene sammen med forskjellige konfidensintervall, vil du se om det er sannsynlighet for at kurvene krysser. Det er i praksis det som ligger bak NIPU analysen som ble presentert på ESMO.

[Laaarsas]

Såhär då: är nuvarande form på KM-kurvorna det mest sannolika utfallet (dvs att det kommer kvarstå en sen korsning), eller går det att modellera ett bättre antagande utifrån tillgängliga data? Går det att åtminstone beräkna fragiliteten för att korsningen består (hänger det endast på ett fåtal patienter?) samt ev sannolikheten att den försvinner?

Och eftersom justerat HR var 0,73: finns det skäl att tro att i en större fas 3 studie med stratifierad randomisering med jämnare fördelning, är sannolikheten för att att en sen korsning uppstår mindre?

[ketilaaj]

Jeg mener at formen på KM plottet som er vist ikke er det mest sannsynlige utfallet, men at det er det mest sannsynlige utfallet av forholdet mellom armene. Dataene i dag gir HR=0.73 og 80%CI på 0.53-1.00.

Etterhvert som dataene modnes forventer jeg at KM kurven for begge armene blir presset nedover (kontrollarmen mest) og at kulene glattes ut slik at kryssingen forsvinner. Når kurvene glattes og kryssingen forsvinner betyr det mindre avvik fra “best fit” kurven, og dermed lavere konfidensintervall.

Så, basert på dataene presentert for NIPU studien, at ipi+nivo og UV1 har proporsjonal virkning under hele behandlingen og mine forventninger om hvordan dataene modnes og at dataene er overførbare til en fase 3 studie, så anser jeg det som lite sannsynlig at kurvene kommer til å krysse i et større fase 3 studie.

[TekBot]

Ultimovacs Announces Webcast to Elaborate on the Results from Randomized UV1 Phase II NIPU Trial in Malignant Mesothelioma

NON-REGULATORY PRESS RELEASE

…

Vis børsmeldingen

Oslo, October 25, 2023: Ultimovacs ASA (“Ultimovacs”) (OSE ULTI), a clinical-
stage biotechnology leader in novel immunotherapeutic cancer vaccines, today
announces that the Company will host a webcast presentation and discussion of
the results from the NIPU study presented at the ESMO Congress 2023.

The results from the randomized Phase II trial showed that Ultimovacs’ cancer
vaccine UV1, in combination with ipilimumab and nivolumab, demonstrated a
statistically significant and clinically meaningful improvement of overall
survival versus ipilimumab and nivolumab alone, a key secondary endpoint. Twice
as many patients in the UV1 arm responded to treatment. No additional safety
concerns were reported from the UV1 treatment.

The positive outcome from the NIPU study is the first demonstration of a
universal cancer vaccine efficacy in a randomized Phase II clinical trial,
showing Proof of Concept and supporting further clinical development as per
investigators’ recommendation.

NIPU (NCT04300244 (CTG Labs - NCBI)) is an
investigator-initiated, randomized, multi-center, open-label Phase II clinical
trial for second-line treatment in patients with malignant mesothelioma (MPM).
The data from the study was published initially
(NewsWeb) in a late-breaking abstract
(https://www.annalsofoncology.org/article/S0923-7534(23)04266-7/fulltext) at the
ESMO Congress in Madrid. Further details were provided in an oral presentation
by the Principal Investigator at the ESMO Congress and was detailed in a press
release (NewsWeb) announced by the Company on
Monday, October 23, 2023.

This webcast follows the presentation of the NIPU results at ESMO by the
Principal Investigator, Professor Åslaug Helland, MD, PhD. The webcast held in
Madrid on Monday, October 23, 2023, had technical difficulties due to unexpected
bandwidth issues at the premises.

The webcasts will take place on Tuesday, October 31, 2023, at:

9:00 am CET (in Norwegian): Link
(https://channel.royalcast.com/landingpage/hegnarmedia/20231031_2/)

2:00 pm CET/ 8:00 am ET (in English): Link
(https://channel.royalcast.com/landingpage/hegnarmedia/20231031_3/)

The webcasts can be accessed live or as a replay. Questions can be sent during
the webcast, or in advance to IR@ultimovacs.com (mailto:IR@ultimovacs.com)

UV1 is a therapeutic cancer vaccine used to generate an immune response against
the enzyme human telomerase (hTERT). The enzyme is essential for the ability of
cancer cells to proliferate. Telomerase is present in 85-90% of all cancers,
across the stages of the disease. The vaccine is manufactured as an off-the-
shelf product with a long shelf life. UV1 is easy to use and does not require
sophisticated hospital infrastructure, enabling patient access to therapy also
in community centers, and in rural and underserved communities.

Ultimovacs is evaluating the universal cancer vaccine UV1 in a broad clinical
development program across various cancer indications with different biology and
disease stages, in combination with different checkpoint inhibitors. The topline
data from NIPU are the first results among the five randomized trials in the UV1
Phase II clinical program. In addition to malignant 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 expected during the first
and second half of 2024. UV1 is a patented, proprietary technology owned by
Ultimovacs.

                                ==ENDS==

About Ultimovacs
Ultimovacs is a clinical-stage biotechnology leader in novel immunotherapeutic
cancer vaccines with broad applicability. Ultimovacs’ lead cancer vaccine
candidate UV1 is directed against human telomerase (hTERT), an antigen present
in 85-90% of cancers in all stages of tumor growth. A broad clinical program,
with Phase II trials in five cancer indications enrolling more than 670
patients, aims to demonstrate UV1’s impact in combination with other
immunotherapies in multiple cancer types expressing telomerase and where
patients have unmet medical needs. UV1 is universal, off-the-shelf and easy to
use, and is a patented technology owned by Ultimovacs.
In addition, Ultimovacs’ adjuvant platform, based on the proprietary Tetanus-
Epitope-Targeting (TET) technology, combines tumor-specific antigens and
adjuvant in the same molecule and is in Phase I clinical development. The
Company is listed on Euronext Oslo Stock Exchange (ULTI.OL).

For further information, please see www.ultimovacs.com or contact:

Carlos de Sousa, CEO
Email: carlos.desousa@ultimovacs.com
Phone: +47 908 92507

Anne Worsøe, Head of IR & Communication
Email: anne.worsoe@ultimovacs.com
Phone: +47 906 86815

This stock exchange announcement was published by Anne Worsøe, Head of IR at
Ultimovacs ASA, on October 25, 2023 at 17:45 CET.

Kilde

[Teddy1]

Bekreftelsen på at selskapet mener markedet har misforstått data.

[Chapman]

Nei! Det er en re-doing fra webcast i Madrid. Ikke begynn

[pdx]

Feil tråd

[RULE]

jeg er ikke ekspert på området, men kan man sige noget om at når ORR er 2x så høj så vil KM plot også konvergere imod en effekt der er bedre end kontrolarmen…? Og dermed hvis der var nok patienter vil kurverne være fint separeret…?

[WernerVonHaussenberg]

ORR vil vises i OS. Og OS er det vi ser på i KM-plottet som er diskutert over.

I posten over (for en dag siden) skriver ketilaaj at han anser det:

@ketilaaj

som lite sannsynlig at kurvene kommer til å krysse i et større fase 3 studie.

I en fase III studie snakker vi trolig om minst 5-600 pasienter.

I NIPU (som er fase II-studie) er det 118 pasienter. Ca. 70 av disse er døde. Resten er sensurerte (betyr at de allerede er estimert inn i plottet der man tror de får OS-event). Kanskje vil de gjenlevende pasientene gjøre at armene skiller seg, kanskje ikke. Vi får neppe svaret på det før jul, og mest sannsynlig ikke før ASCO-konferansen i juni 2024.

Dette innlegget og spørsmålet + de to over det igjen hører hjemme i småprat. La oss prøve å holde fundamental ryddig.

[TekBot]

Ultimovacs Announces Protocol Amendment in UV1 Phase II Study INITIUM in Malignant Melanoma, Enabling Data Readout in First Half of 2024

• Patients in the INITIUM study are taking longer than expected to experience
  cancer progression. Reaching the number of progressing patients required for
  readout may take several months or even years, which has justified an
  …

Vis børsmeldingen

amendment of the study protocol.

• The amended protocol in INITIUM enables the data analysis to start mid-
  January 2024 after the last enrolled patient has been followed up for 18
  months. The topline results from the randomized Phase II study are expected
  to be announced approximately two to three months later.

• INITIUM completed enrollment of 156 patients in July 2022. The results from
  the randomized trial will provide comparative data on efficacy and safety
  for UV1 treatment in malignant melanoma added to standard-of-care
  immunotherapy, ipilimumab and nivolumab.

Oslo, October 31, 2023: Ultimovacs ASA (“Ultimovacs”) (OSE ULTI), a clinical-
stage biotechnology leader in novel immunotherapeutic cancer vaccines, today
announced that the analysis of the INITIUM data will be initiated in mid-January
2024, following an amendment of the clinical trial protocol. The INITIUM
protocol has been amended to allow data readout based on a minimum of 18-month
follow-up of all evaluable patients, at which time the patients have a mean
follow-up time of 24 months. The amendment will maintain the integrity of the
study statistics.

The protocol amendment was submitted to the regulatory authorities in the
countries where the INITIUM trial is conducted: The U.S. Food and Drug
Administration (FDA) and regulatory bodies in Belgium, Norway, and the U.K. The
FDA has not issued any objections to the amendment and the Regulatory
Authorities in two European countries have approved the amendment with one
pending.

The INITIUM study (NCT04382664
(CTG Labs - NCBI)) evaluates
Ultimovacs’ universal cancer vaccine, UV1, as first-line treatment in
unresectable or metastatic malignant melanoma in combination with PD-1
checkpoint inhibitor nivolumab and CTLA-4 checkpoint inhibitor ipilimumab. The
first patient was enrolled in June 2020, and the trial completed enrollment of
156 patients in July 2022. Per the original trial protocol, data analysis would
be conducted after cancer progression or death has been verified in 70 patients.

Based on published historical references, progression was estimated to occur in
70 patients by the first half of 2023. With the current development in patient
progression, reaching these 70 events could take many months or even years,
justifying the decision to implement the protocol amendment. Based on the recent
acceptance from the regulators, the data can now be analyzed in early 2024,
enabling Ultimovacs to maintain its guidance on reporting the outcome of the
study two to three months later in the first half of 2024.

“We are pleased for the patients in the INITIUM study that it takes longer than
anticipated to experience progression of the disease. With positive survival
results from the first randomized Phase II study in malignant mesothelioma, a
very hard-to-treat cancer, we are increasingly optimistic about UV1’s potential
to benefit cancer patients. As we seek to bring UV1 to the patients as quickly
as possible, it is important to advance the INITIUM trial towards a data
readout,” said Carlos de Sousa, CEO of Ultimovacs. “We appreciate the support
from regulatory authorities, and we now look forward to sharing the results in
the first half of 2024.”

The primary endpoint of the Phase II study INITIUM is progression-free survival
(PFS) as per RECIST 1.1. Secondary endpoints include overall survival (OS),
objective response rate (ORR), duration of response (DOR), and safety of UV1
vaccination in combination with nivolumab and ipilimumab.

Ultimovacs has received a dual Fast Track designation from the FDA, granted in
October 2021 (https://ultimovacs.com/investors/news/ultimovacs-receives-dual-
fda-fast-track-designation-for-uv1-in-advanced-malignant-melanoma), for UV1 in
combination with checkpoint inhibitors in the treatment of unresectable or
metastatic melanoma - either as add-on therapy to pembrolizumab or as add-on
therapy to ipilimumab. In December 2021
(https://ultimovacs.com/investors/news/ultimovacs-granted-orphan-drug-
designation-by-fda-for-uv1-cancer-vaccine-in-metastatic-melanoma), UV1 was
granted Orphan Drug designation from the FDA for treatment of stage IIB-IV
melanoma.

UV1 is a therapeutic cancer vaccine used to generate an immune response against
the enzyme human telomerase (hTERT). The enzyme is essential for the ability of
cancer cells to proliferate. Telomerase is present in 85-90% of all cancers,
across the stages of the disease. The vaccine is manufactured as an off-the-
shelf product with a long shelf life. UV1 is easy to use and does not require
sophisticated hospital infrastructure, enabling patient access to therapy also
in community centers, and rural and underserved communities.

Ultimovacs is evaluating the universal cancer vaccine UV1 in a broad clinical
development program across various cancer indications with different biology and
disease stages, combined with different checkpoint inhibitors. The topline data
from INITIUM will be the second readout among the five randomized trials in the
UV1 Phase II clinical program. In October 2023, the UV1 Phase II trial NIPU in
malignant mesothelioma reported a clinically meaningful overall survival benefit
in the patients receiving UV1 vaccination, with no added toxicities. Per
protocol, the overall survival results were statistically significant. In
addition to the studies in malignant melanoma and malignant mesothelioma, Phase
II studies are ongoing in patients with head and neck cancer (FOCUS), ovarian
cancer (DOVACC), and non-small cell lung cancer (LUNGVAC). The data from the
FOCUS trial is expected in the second half of 2024.

                                ==ENDS==

About INITIUM
INITIUM is an Ultimovacs-sponsored randomized, comparative, multicenter Phase II
trial in which the universal cancer vaccine UV1 will be evaluated in combination
with the checkpoint inhibitors ipilimumab and nivolumab for first-line treatment
of patients with unresectable or metastatic malignant melanoma. The first
patient received treatment in the INITIUM trial in June 2020, and the last
patient was enrolled in July 2022. The study was conducted at 39 hospitals
across the U.S., U.K., Belgium, and Norway. The initial study design called for
enrollment of 154 patients. Two additional patients were enrolled bringing the
total number of patients in the study to 156.

About Ultimovacs

Ultimovacs is a clinical-stage biotechnology leader in novel immunotherapeutic
cancer vaccines with broad applicability. Ultimovacs’ lead cancer vaccine
candidate UV1 is directed against human telomerase (hTERT), an antigen present
in 85-90% of cancers in all stages of tumor growth. A broad clinical program,
with Phase II trials in five cancer indications enrolling more than 670
patients, aims to demonstrate UV1’s impact in combination with other
immunotherapies in multiple cancer types expressing telomerase and where
patients have unmet medical needs. UV1 is universal, off-the-shelf, and easy to
use, and is a patented technology owned by Ultimovacs.

In addition, Ultimovacs’ adjuvant platform, based on the proprietary Tetanus-
Epitope-Targeting (TET) technology, combines tumor-specific antigens and
adjuvant in the same molecule and is in Phase I clinical development.
The Company is listed on the Euronext Oslo Stock Exchange (ULTI.OL).

About the UV1 Phase II program

The immunotherapeutic cancer vaccine UV1 is investigated in combination with
checkpoint inhibitors in patients with various cancer indications with diverse
tumor biology. The diversity of the UV1 Phase II program places Ultimovacs in a
favorable position to capture the cancer vaccine’s potential broad applicability
when combined with checkpoint inhibitors:

• INITIUM: Evaluating UV1 in combination with ipilimumab and nivolumab as
  first-line treatment for patients with malignant melanoma. Enrollment of
  156 patients completed in July 2022. As of the Q2 2023 report, 70 events
  were not reached. Expected readout H1 2024. Sponsored by Ultimovacs.
• NIPU: Evaluating UV1 in combination with ipilimumab and nivolumab as second-
  line treatment for patients with malignant pleural mesothelioma. Enrollment
  of 118 patients completed in January 2023. Data presented at the ESMO
  Congress in October 2023, showed that UV1 as an add-on to ipilimumab and
  nivolumab, demonstrated a statistically significant and clinically
  meaningful improvement in overall survival versus ipilimumab and nivolumab
  alone. 31% of the patients receiving the UV1 vaccine experienced an
  objective response, compared to 16% in the control arm. The investigator-
  initiated study is led by Oslo University Hospital and supported by Bristol-
  Myers Squibb and Ultimovacs.
• FOCUS: Evaluating UV1 in combination with pembrolizumab as first-line
  treatment for patients with head and neck cancer. Enrollment of 75 patients
  completed in August 2023, expected readout H2 2024. The investigator-
  initiated study is led by Halle University in Germany, supported by
  Ultimovacs.
• DOVACC: Evaluating UV1 in combination with olaparib and durvalumab as
  maintenance therapy in non-BRCA mutated patients with advanced ovarian
  cancer. >20% of 184 patients enrolled as of Q2 2023 reporting, expected
  readout H2 2024. The investigator-initiated study is led by NSGO-CTU and
  supported by ENGOT, AstraZeneca, and Ultimovacs.
• LUNGVAC: Evaluating UV1 combined with cemiplimab as first-line treatment of
  non-small cell lung cancer patients. <10% of 138 patients enrolled as of Q2
  2023 reporting, expected readout H2 2025. The investigator-initiated study
  is led by Vestre Viken (Drammen Hospital) and supported by Ultimovacs.

About UV1

UV1 is a universal cancer vaccine designed to induce a specific T-cell response
against telomerase. UV1 consists of long, synthetic peptides representing a
sequence in the reverse transcriptase subunit of telomerase (hTERT), shown to
induce CD4+ T-cells. These CD4+ T-cells have the potential to provide
inflammatory signals, and T-cell support is believed to be critical for
triggering a strong anti-tumor immune response. Following intradermal injection,
antigen-presenting cells (APCs) in the skin are exposed to the vaccine peptides.
These APCs will process the peptides and present vaccine epitopes on Human
Leukocyte Antigen (HLA) molecules to naïve T-cells in the lymph nodes. Activated
vaccine-specific T-cells will then enter the circulation and search for cells
displaying their cognate antigen in the context of HLA molecules.
The UV1 peptides contain several epitopes, shown to be non-restrictive in terms
of (HLA) alleles for presentation. It is, therefore not required to perform HLA
pre-screening of patients, which potentially enables broad population
utilization of the vaccine. UV1 is administered over three months as eight
intradermal injections together with the immune-modulator GM-CSF.

For further information, please contact:

Carlos de Sousa, CEO
Email: carlos.desousa@ultimovacs.com (mailto:carlos.desousa@ultimovacs.com)
Phone: +47 908 92507

Anne Worsøe, Head of Investor Relations
Email: anne.worsoe@ultimovacs.com (mailto:anne.worsoe@ultimovacs.com)
Phone: +47 90686815

This information is considered inside information pursuant to the EU Market
Abuse Regulation and is subject to the disclosure requirements pursuant to
Section 5-12 in the Norwegian Securities Trading Act. This stock exchange
announcement was published by Anne Worsøe, Head of Investor Relations at
Ultimovacs ASA, on October 31, 2023 at 07:00 CET.

Kilde

[Martins]

INITIUM P2 Trial opening: 15. january ± 5 days
INITIUM P2 Trial readout analysis results: 10. march-20. april
Primary endpoint: PFS, Secondary endpoints: OS, ORR, DOR, safety

NIPU P2 Update OS, ORR, PFS, DOR, safety: ASCO 2024 (31.5-4.6 2024)
FOCUS P2 Trial readout analysis expected: H2 2024 (1.7-31.12.2024)
DOVACC P2 Trial readout analysis results expected: H2 2024 (1.7-31.12 2024)
LUNGVAC P2 Trial readout analysis results expected: H2 2025 ( 1.7-31.12 2025)

TET P1: TBA

Q3 rapport: 8. november 2023

Generalforsamling: ca. 20. april 2024

Unknowns:

Emi: estimert april-mai 2024
Søknader til FDA/Europeiske myndigheter basert på NIPU data: Svar 31.okt-feb. 2024 en gang
Avtaler basert på NIPU data: Svar 31.okt-juni 2024 en gang
Søknader andre indikasjoner for UV1: TBA
BMS takeover: TBA

[Smacks]

NIPU update: ASCO 24?

[polygon]

En PFS-event er progresjon i sykdom eller død. Man kan ikke lese direkte ut av et KM-plot for PFS hva som er hva. Død vil i de aller fleste tilfeller være som følge av forutgående progresjon i sykdommen, men pga. raskt sykdomsforløp, ventetid og logistikk så vil man i en del tilfeller ikke ha bilder fra et tidspunkt der progresjon kunne ha blitt påvist. Og radiologene vil i en del tilfeller ikke konkludere med progresjon selv om man har bilder fra et “riktig” tidspunkt. Av disse grunnene vil en del dødsfall ikke ha definert progresjon i forkant. Eller sagt på en annen måte: I en del tilfeller vil en OS-event definere en PFS-event.

Fra NIPU har vi nå to PFS-plot og et OS-plot. Jeg har lagt de tre KM-plottene over hverandre, skalert slik at x-aksene blir like, zoomet inn og så tegnet en haug med vertikale streker. Da har jeg funnet ut følgende:

• I UV1 armen har 4 OS-eventer definert PFS-eventer både lokalt og sentralt
• i SoC armen har 7 OS-eventer definert PFS-eventer både lokalt og sentralt

Hele tanken bak PFS som et surrogatendepunkt for OS er at progresjon skal avdekkes og komme som et datapunkt før OS. Det er derfor et mål at man skal klare å avdekke progresjon i sykdommen før evt. død i den enkelte pasient. I alle de pasientene som ikke både lokal og sentral bedømming har latt en OS-event definere en PFS-event for, så vil man nødvendigvis hatt bilder og vurdere ut i fra. Da har man hatt muligheten til å avdekke en PFS-event før en OS-event. Dersom radiologene da har vært kompetente, så vil det alt annet likt være færre heller en flere PFS-eventer som er definert av en OS-eventer fra disse. Og hvordan ser forskjellen på lokal og sentral bedømming av PFS ut i dette henseende?

• I UV1 armen har 6 OS-eventer definert PFS-eventer lokalt
• I SoC armen har 9 OS-eventer definert PFS-eventer lokalt
• I UV1 armen har 10 OS-eventer definert PFS-eventer sentralt
• I SoC armen har 15 OS-eventer definert PFS-eventer sentralt

Jeg mener man av dette alene kan konkludere med at lokale radiologer gjorde en kvalitativt bedre vurdering av bildene. Lokal vurdering konkluderte som kjent med en høyst signifikant forskjell mellom armene til fordel for eksperimentell arm.

En feilkilde til metoden er at man kan ha hatt en definert PFS-event helt samtidig med en OS-event fra en pasient som tidligere har hatt en PFS-event. Men at disse inntreffer eksakt samtidig er ikke særlig sannsynsynlig, og nuller uansett ikke denne store forskjellen mellom lokal og sentral.

[Fartin]

Jøss. Her levere du på ett nivå som kanskje Helland burde få vite om. Men de er kanskje på saken.