Vis børsmeldingen
nivolumab alone, in the second-line treatment of patients with malignant
mesothelioma
-
The UV1 cancer vaccination combined with ipilimumab and nivolumab reduced
the risk of death by 27%, meeting the protocol predefined threshold for
statistical significance, in a hard-to-treat patient group with currently no
standard-of-care treatment options
-
First demonstration of universal cancer vaccine efficacy and therapeutic
impact in a randomized Phase II clinical trial, supporting further clinical
development
-
NIPU results to be presented by the Principal Investigator Professor Åslaug
Helland (https://www.esmo.org/about-esmo/biographies/aaslaug-helland), MD,
Ph.D., at the ESMO Congress 2023 happening this week in Madrid
-
The full dataset will be shared in a separate press release and at the
Company website after the Principal Investigator’s oral presentation,
Saturday October 21, 2023 at 15:15 (CET)
-
Webcast with the Principal Investigator and Ultimovacs management to take
place
on Mon, Oct 23 2023 at 14:30 (CET) <Link
(https://channel.royalcast.com/hegnarmedia/#!/hegnarmedia/20231023_2) to
webcast>
Oslo, October 17, 2023: Ultimovacs ASA (“Ultimovacs”) (OSE ULTI), a clinical-
stage biotechnology leader in novel immunotherapeutic cancer vaccines, today
announced the results from the NIPU clinical trial (NCT04300244
(CTG Labs - NCBI)), an investigator-initiated,
randomized, multi-center, open-label Phase II clinical trial for second-line
treatment in patients with malignant mesothelioma. The data presented as a late-
breaking abstract at the ESMO Congress, shows 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. No additional safety
concerns were reported from the UV1 treatment. The late-breaking abstract is
accessible at the ESMO website.
Malignant mesothelioma is considered an aggressive, complex form of cancer with
a high mortality rate and few therapeutic options. Patients affected have often
been occupationally or environmentally exposed to asbestos. Several efforts have
been made in the last decades to improve the survival outcomes of patients with
mesothelioma. There is currently no established standard of care in second-line
treatment.
“For patients with malignant mesothelioma, few treatment options are available
after first-line chemotherapy. The NIPU study showed that patients receiving UV1
vaccination as add-on to nivolumab and ipilimumab experienced an increased
objective response rate and a clinically meaningful prolonged survival. These
encouraging results provide a foundation for advancing further clinical
development with UV1 vaccination in mesothelioma patients,” said Principal
Investigator of the NIPU clinical trial, Professor Åslaug Helland, MD Ph.D. “We
want to extend our gratitude to the patients and their families, as well as the
dedicated investigators and all our supporters whose invaluable contributions
made this study possible.”
The results showed that UV1 plus ipilimumab and nivolumab improved overall
survival (OS), reducing the risk of death by 27% (HR=0.73 [80% CI, 0.53-1.00]).
The median OS was 15.4 months (95% CI, 11.1-22.6) for UV1 plus ipilimumab and
nivolumab (treatment arm) versus 11.1 months (95% CI, 8.8-18.1) for ipilimumab
and nivolumab alone (control arm), with a median observation time of 17.3
months. This degree of improvement met protocol predefined threshold for
statistical significance.
The data further demonstrated a benefit in terms of objective response rate, as
determined by a blinded independent central review. In the UV1 arm, 31% of the
patients experienced an objective response, as compared to 16% in the control
arm (odds ratio 2.44 [80% CI, 1.35-4.49]).
The safety profile of the combination of UV1 plus ipilimumab and nivolumab
observed in the trial was consistent with the safety profile of ipilimumab and
nivolumab alone, confirming the good safety profile for UV1. The patients will
continue to be monitored for efficacy and safety endpoints over the next years.
The title of the late-breaking ESMO abstract 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.”
“We are thrilled to announce the highly advantageous results from the first
randomized UV1 Phase II trial, marking a major milestone for Ultimovacs. Overall
survival is the ‘gold standard’ in cancer treatment. We believe these data
supports further development in mesothelioma, and we are looking forward to
discussing the results with the regulatory authorities,” said Carlos de Sousa,
CEO of Ultimovacs. “UV1, by demonstrating significant survival improvement in a
hard-to-treat indication as malignant mesothelioma, shows that universal cancer
vaccines are a treatment modality with the potential to improve the current
treatment regime for cancer patients globally. The encouraging NIPU results
heighten our optimism and raise our expectations for favorable results in the
four additional ongoing UV1 Phase II trials. I would like to thank everyone who
has contributed, especially Professor Åslaug Helland, who invited us to
participate in the study, and Bristol-Meyers Squibb for their valuable
contribution.”
The NIPU study is sponsored by Oslo University Hospital with support from
Bristol-Myers Squibb and Ultimovacs. The randomized, open-label, multi-center
trial with 118 patients conducted in Australia, Denmark, Norway, Spain, and
Sweden, was designed to investigate if combining UV1 with checkpoint inhibitors
ipilimumab and nivolumab would provide a benefit compared to ipilimumab and
nivolumab alone, in patients with malignant mesothelioma after first-line
treatment with platinum-based chemotherapy. The first patient in the NIPU trial
was enrolled in June 2020, and the last patient was enrolled in January 2023.
The NIPU study announced topline results in June 2023. Based on blinded
independent central review (BICR), the study did not meet the primary endpoint
of PFS. Investigator assessment, a pre-defined supportive analysis of the
primary endpoint performed by specialized radiologists at the study hospitals,
showed a statistically significant positive PFS benefit for the patients in the
UV1 arm. The HR per BICR was 1.01 (80% CI 0.75-1.36), with a median PFS of 4.2
months (95% CI 2.9-9.8) for UV1 plus ipilimumab and nivolumab, and 4.7 months
(95% CI 3.9-7.0) for ipilimumab and nivolumab alone. The HR per investigator
assessment was 0.60 (80% CI 0.45-0.81), with a median PFS of 4.3 months (95% CI
3.0-6.8) for UV1 plus ipilimumab and nivolumab and 2.9 months (95% CI 2.4-5.5)
for ipilimumab and nivolumab alone.
The data from June 2023 showed a positive trend of improvement in overall
survival in the UV1 arm over the control arm, but the data needed to mature
before a conclusion could be reached. As of August, with a median observation
time of 17.3 months, the data presented at ESMO demonstrates survival benefit
for patients receiving the UV1 vaccine in the NIPU study.
In October 2023, Ultimovacs announced that FDA had granted Orphan Drug
Designation for UV1 in the treatment of mesothelioma (based on the NIPU data
from June 2023).
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 biologies
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 NIPU
NIPU (Nivolumab and Ipilimumab Plus/minus UV1 vaccination) is a randomized,
multi-center phase II trial in which Ultimovacs’ universal cancer vaccine, UV1,
is evaluated in combination with Bristol-Myers Squibb’s checkpoint inhibitors,
nivolumab and ipilimumab, as second-line treatment of malignant mesothelioma.
The trial sponsor is Oslo University Hospital, supported in the preparation and
execution of the trial by Ultimovacs and Bristol-Myers Squibb.
The 118 patients are randomized 1:1 into two treatment arms. All participants
receive treatment with nivolumab (240 mg every 2 weeks) and ipilimumab (1 mg/kg
every 6 weeks) until disease progression, unacceptable toxicity or for a maximum
of 2 years. Patients randomized to the experimental arm received 8 intradermal
injections of UV1 vaccine during the first three months of treatment. The
objective of the study is to achieve a clinically meaningful benefit in patients
with malignant mesothelioma (MPM) after progression on first-line standard
platinum doublet chemotherapy. Subsequent events emerging in patients in both
arms of the NIPU study will continue to be monitored beyond read-out of the
primary endpoint. The ipilimumab and nivolumab combination has recently been
approved as first-line treatment for patients with malignant pleural
mesothelioma in Europe and the U.S.
The trial was sized to detect a target PFS HR of 0.6, with 80% power and a 1-
sided alpha of 0.1. Overall survival was calculated using the same method as for
PFS.
About Mesothelioma
Malignant mesothelioma is a rare and aggressive type of cancer that occurs in
the thin layer of tissue that surrounds the lungs and inside of the chest.
Mesothelioma accounted for 30 870 new cancer cases and 26 278 cancer deaths
worldwide in 2020, according to International Agency for Research on Cancer
(Globocan 2020). Mesothelioma is a disease with a high unmet medical need,
especially in industrialized countries. The median overall survival is
approximately 1 year. Occupational asbestos exposure is the No. 1 cause of the
disease, and several occupations like firefighters, military veterans,
construction, and industry workers, are at risk. This cancer usually takes
several decades to develop after a person’s first exposure to asbestos. Most
patients are diagnosed after age 70 because of the long latency period. Even
though the use of asbestos to a large extent is banned in new constructions in
many countries today, new incidences of mesothelioma will continue to be a
medical and public health challenge because of the long latency period typical
of the illness. For patients with inoperable disease, few treatment options are
available after first-line chemotherapy. The combination of ipilimumab and
nivolumab has recently shown increased survival compared to standard
chemotherapy, but most patients do not respond, and improvements are called for.
Telomerase is expressed in mesothelioma cells and is therefore a relevant target
for therapeutic vaccination.
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).
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. 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; results will be presented at the ESMO Congress in
October 2023. 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, 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.
A link to the webcast and the comprehensive results from the NIPU study may be
accessed from the Company website www.ultimovacs.com
(http://www.ultimovacs.com). For further information, please contact:
Carlos de Sousa, CEO
Email: [email protected] (mailto:[email protected])
Phone: +47 908 92507
Anne Worsøe, Head of Investor Relations
Email: [email protected] (mailto:[email protected])
Phone: +47 90686815
This information is considered to be 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 17, 2023 at 18:05 CET.
Kilde
