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survival benefit with no added toxicities, compared to ipilimumab and
nivolumab alone, in the second-line treatment of patients with malignant
mesothelioma
Oslo, October 23, 2023: Ultimovacs ASA (“Ultimovacs”) (OSE ULTI), a clinical-
stage biotechnology leader in novel immunotherapeutic cancer vaccines, today
announced the full dataset from the NIPU clinical trial (NCT04300244
(CTG Labs - NCBI)) presented at the ESMO Congress
2023 in Madrid. NIPU 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
ESMO. Further details have now been provided in an oral presentation by the
Principal Investigator at the ESMO Congress. The results showed that Ultimovacs’
cancer vaccine UV1, in combination with ipilimumab and nivolumab, demonstrated a
statistically significant and clinically meaningful improvement in overall
survival versus ipilimumab and nivolumab alone, a key secondary endpoint. No
additional safety concerns were reported from the UV1 treatment.
UV1 plus ipilimumab and nivolumab improved overall survival (OS), reducing the
risk of death by 27% (hazard ratio (HR)=0.73 [80% CI, 0.53-1.00], 1-sided p
value = 0.0985, 2-sided p value = 0.197). 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 the
protocol’s predefined threshold for statistical significance.
The data further demonstrated a benefit in terms of objective response rate
(tumor reduction by at least 30%), as determined by blinded independent central
review (BICR). In the UV1 arm, 31% of the patients experienced an objective
response, compared to 16% in the control arm (odds ratio 2.44 [80% CI,
1.35-4.49], 1-sided p value = 0.028).
The baseline patient characteristics were well balanced between the two
treatment arms. The epithelioid subtype of MPM comprised 77.1% of the study
population, in line with the frequency of this subtype among the general MPM
population. Notably, the trial enrolled a relatively high fraction of patients
with PD-L1 negative tumor biopsies (53.4%), a characteristic for patients
typically less responsive to checkpoint inhibitors alone.
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 results from the first randomized UV1 Phase II trial, NIPU presented by the
Principal Investigator Professor Åslaug Helland at ESMO 2023, is a proof of
concept for UV1. These data reaffirm our unwavering commitment to developing UV1
as an effective add-on treatment to checkpoint inhibitors for a range of
cancers. We eagerly anticipate the forthcoming results from our other ongoing
Phase II trials and how these data will move us forward in our mission to
improve outcomes for cancer patients worldwide,” said Carlos de Sousa, CEO of
Ultimovacs.
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 was conducted in Australia, Denmark, Norway, Spain, and
Sweden. The trial enrolled 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 trial was designed to detect a clinically meaningful difference between
the two treatment groups and includes a statistical analysis plan typical for
randomized phase 2 trials where the aim is to assess efficacy without recruiting
a large number of patients. Both the study protocol and the statistical plan
were approved by the regulatory authorities. It was set up with 80% statistical
power and a 1-sided alpha of 0.1. This means we can be 80% confident that we’ve
accurately measured the effects of UV1. According to the trial protocol and the
number of patients included, the trial results are presented with 80% confidence
intervals and are considered statistically significant if the one-sided p-value
is below 0.1.
Ultimovacs announced topline NIPU study results in June 2023. Based on 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, 1-sided p value = 0.4895, 2-sided p value = 0.979), 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, 1-sided p value = 0.0125, 2-
sided p value = 0.025), 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.
In October 2023, Ultimovacs announced that the U.S. Food and Drug Administration
(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 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 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 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 were randomized 1:1 into two treatment arms. All participants
receive treatment with nivolumab (240 mg every two weeks) and ipilimumab (1
mg/kg every six weeks) until disease progression, unacceptable toxicity, or for
a maximum of 2 years. Patients randomized to the experimental arm received eight
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 the
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 surrounding 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 the 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 one 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. Few treatment options are available after first-line
chemotherapy for patients with inoperable disease. 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.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, 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, the results were 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 with eight
intradermal injections and 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: 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 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 23, 2023 at 07:00 CET.
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