Ivonescimab alone or combined with chemotherapy
led to intracranial responses among 34% of patients with brain
metastases at baseline – 23% achieved a complete response
All patients who did not achieve an
intracranial response demonstrated stable disease or
non-progression by RANO criteria irrespective of cohort
Median intracranial PFS of 19.3 months observed
across combined cohorts of ivonescimab administered as monotherapy
or in combination with chemotherapy
No cases of intracranial bleeding were observed
in these patients with brain metastases
Detailed safety and anti-tumor activity updates
from Phase II trial for ivonescimab plus chemotherapy in multiple
NSCLC settings, including 1L squamous NSCLC
Summit Therapeutics Inc. (NASDAQ: SMMT) (“Summit,” “we,” or the
“Company”) today announced promising data for its novel, potential
first-in-class investigational bispecific antibody, ivonescimab,
that is being presented today at the 2024 European Lung Cancer
Congress (ELCC 2024) in Prague, Czech Republic. Two posters
featuring updated ivonescimab data will be displayed from 12:00 to
12:45pm Central European Time. The posters will also be made
available on our website after the presentation period.
The first poster, “Intracranial Activity of Ivonescimab Alone or
in Combination with Platinum Doublet Chemotherapy in Patients with
Advanced Non-Small Cell Lung Cancer (NSCLC) and Brain Metastases”
includes data from patients with asymptomatic brain metastases at
baseline. These patients were enrolled in either AK112-202
(NCT04900363), in which ivonescimab is delivered as monotherapy, or
AK112-201 (NCT04736823), in which ivonescimab is delivered in
combination with platinum doublet chemotherapy, both of which are
Phase II clinical trials for patients with advanced or metastatic
NSCLC. This analysis consisted of the 35 patients with advanced or
metastatic NSCLC who had asymptomatic brain metastases at baseline;
28 patients were treated with ivonescimab plus chemotherapy in
AK112-201, and seven patients were treated with monotherapy
ivonescimab in AK112-202.
Notably, median intracranial progression-free survival was 19.3
months across all patients analyzed. Patients across both cohorts
experienced an intracranial response rate of 34%, and eight
patients (23%) experienced a complete response by RANO criteria.
All patients who did not achieve a response demonstrated stable
disease or non-progression; no patients experienced intracranial
disease progression at the time of the initial follow-up scan. No
cases of intracranial bleeding complications were observed in these
patients.
“We are pleased to see ivonescimab’s favorable intracranial
response rates and median intracranial progression-free survival as
well as promising anti-tumor activity and safety profile in the
subgroup of patients with brain metastases from NSCLC,” said Dr. H.
Jack West, Vice President of Clinical Development at Summit. “We
are grateful for the patients and clinical investigators supporting
these trials, and our ongoing collaboration with our partners at
Akeso.”
The second poster titled, “Phase 2 Results of Ivonescimab a
Novel PD-1/VEGF Bispecific in Combination with Chemotherapy for
First Line Treatment of Patients with Advanced / Metastatic
Non-Small Cell Lung Cancer” includes updated data from the Phase II
trial AK112-201 centered around the cohort of patients in which
ivonescimab is combined with chemotherapy for first-line treatment
of squamous and non-squamous advanced or metastatic NSCLC in
patients without actionable genomic alterations (e.g., positive for
endothelial growth factor receptor (EGFR) mutations or anaplastic
lymphoma kinase (ALK)). Summarized updates in NSCLC patients with
EGFR mutations after a tyrosine kinase inhibitor (TKI) and NSCLC
patients who have received prior PD-(L)1 plus doublet chemotherapy
treatment are included as well.
Of significance, first-line advanced or metastatic squamous
NSCLC patients experienced a median PFS of 11.1 months (95% CI: 9.5
– 16.3 months). In addition, first-line patients with advanced or
metastatic non-squamous tumors experienced a median PFS of 13.3
months (95% CI: 8.3 – 16.4 months). Median overall survival was not
reached in either subset of patients after a median follow-up time
of 22.1 months. The frequency of treatment-emergent adverse events
(TEAEs) leading to the discontinuation of ivonescimab was 11.1% and
2.8%, respectively, in patients with squamous and non-squamous
tumors. The most frequent TEAEs were anemia and decreased
neutrophil counts in squamous patients and anemia and constipation
in non-squamous patients.
The posters will be presented by, amongst others, Dr. Li Zhang,
Sun Yat-Sen University Cancer Center, and Dr. West, with data
generated and analyzed by our collaboration and licensing partner,
Akeso Inc. (HKEX Code: 9926.HK) with contribution by Summit
staff.
Summit continues its clinical development of ivonescimab in
order to establish its efficacy and safety in two NSCLC
indications:
- HARMONi Phase III trial: ivonescimab combined with chemotherapy
in patients with EGFR-mutated, locally advanced or metastatic
non-squamous NSCLC who have progressed after treatment with a
third-generation EGFR TKI (NCT05184712)
- HARMONi-3 Phase III trial: ivonescimab combined with
chemotherapy in first-line metastatic squamous NSCLC patients
(NCT05899608)
About the ELCC 2024 Posters
Poster Title: Phase 2 Results of Ivonescimab a Novel PD-1/VEGF
Bispecific in Combination with Chemotherapy for First Line
Treatment of Patients with Advanced / Metastatic Squamous Non-Small
Cell Lung Cancer ELCC Presentation No.: 68P Session Date &
Time: Friday, March 22, 2024, 12:00 to 12:45pm CET
Poster Title: Intracranial Activity of Ivonescimab Alone or in
Combination with Platinum Doublet Chemotherapy in Patients with
Advanced Non-Small Cell Lung Cancer and Brain Metastases ELCC
Presentation No.: 174P Session Date & Time: Friday, March 22,
2024, 12:00 to 12:45pm CET
About Ivonescimab
Ivonescimab, known as SMT112 in Summit’s license territories,
the United States, Canada, Europe, and Japan, and as AK112 in China
and Australia, is an investigational, novel, potential
first-in-class bispecific antibody combining the effects of
immunotherapy via a blockade of PD-1 with the anti-angiogenesis
effects associated with blocking VEGF into a single molecule.
Ivonescimab displays cooperative binding with each of its intended
targets with higher affinity when in the presence of both PD-1 and
VEGF.
This could differentiate ivonescimab as there is potentially
higher expression (presence) of both PD-1 and VEGF in tumor tissue
and the tumor microenvironment (TME) as compared to normal tissue
in the body. Ivonescimab’s tetravalent structure (four binding
sites) enables higher avidity (accumulated strength of multiple
binding interactions) in the tumor microenvironment with over
18-fold increased binding affinity to PD-1 in the presence of VEGF
in vitro, and over 4-times increased binding affinity to VEGF in
the presence of PD-1 in vitro (Zhong, et al, SITC, 2023). This
tetravalent structure, the intentional novel design of the
molecule, and bringing these two targets into a single bispecific
antibody with cooperative binding qualities have the potential to
direct ivonescimab to the tumor tissue versus healthy tissue. The
intent of this design is to improve upon previously established
efficacy thresholds, in addition to side effects and safety
profiles associated with these targets.
Ivonescimab was discovered by Akeso Inc. (HKEX Code: 9926.HK)
and is currently engaged in multiple Phase III clinical trials.
Over 1,600 patients have been treated with ivonescimab in clinical
studies globally. Summit has begun its clinical development of
ivonescimab in non-small cell lung cancer (NSCLC), commencing
enrollment in 2023 in two Phase III clinical trials.
Ivonescimab is an investigational therapy that is not approved
by any regulatory authority.
About Summit Therapeutics
Summit Therapeutics Inc. is a biopharmaceutical oncology company
focused on the discovery, development, and commercialization of
patient-, physician-, caregiver- and societal-friendly medicinal
therapies intended to improve quality of life, increase potential
duration of life, and resolve serious unmet medical needs.
Summit was founded in 2003 and our shares are listed on the
Nasdaq Global Market (symbol ‘SMMT’). We are headquartered in
Miami, Florida, and we have additional offices in Menlo Park,
California, and Oxford, UK.
For more information, please visit https://www.smmttx.com and
follow us on X @summitplc.
Summit Forward-looking Statements
Any statements in this press release about the Company’s future
expectations, plans and prospects, including but not limited to,
statements about the clinical and preclinical development of the
Company’s product candidates, entry into and actions related to the
Company’s partnership with Akeso Inc., the Company's anticipated
spending and cash runway, the therapeutic potential of the
Company’s product candidates, the potential commercialization of
the Company’s product candidates, the timing of initiation,
completion and availability of data from clinical trials, the
potential submission of applications for marketing approvals,
potential acquisitions, and other statements containing the words
"anticipate," "believe," "continue," "could," "estimate," "expect,"
"intend," "may," "plan," "potential," "predict," "project,"
"should," "target," "would," and similar expressions, constitute
forward-looking statements within the meaning of The Private
Securities Litigation Reform Act of 1995. Actual results may differ
materially from those indicated by such forward-looking statements
as a result of various important factors, including the results of
our evaluation of the underlying data in connection with the
development and commercialization activities for ivonescimab, the
outcome of discussions with regulatory authorities, including the
Food and Drug Administration, the uncertainties inherent in the
initiation of future clinical trials, availability and timing of
data from ongoing and future clinical trials, the results of such
trials, and their success, and global public health crises, that
may affect timing and status of our clinical trials and operations,
whether preliminary results from a clinical trial will be
predictive of the final results of that trial or whether results of
early clinical trials or preclinical studies will be indicative of
the results of later clinical trials, whether business development
opportunities to expand the Company’s pipeline of drug candidates,
including without limitation, through potential acquisitions of,
and/or collaborations with, other entities occur, expectations for
regulatory approvals, laws and regulations affecting government
contracts and funding awards, availability of funding sufficient
for the Company’s foreseeable and unforeseeable operating expenses
and capital expenditure requirements and other factors discussed in
the "Risk Factors" section of filings that the Company makes with
the Securities and Exchange Commission. Any change to our ongoing
trials could cause delays, affect our future expenses, and add
uncertainty to our commercialization efforts, as well as to affect
the likelihood of the successful completion of clinical development
of ivonescimab. Accordingly, readers should not place undue
reliance on forward-looking statements or information. In addition,
any forward-looking statements included in this press release
represent the Company’s views only as of the date of this release
and should not be relied upon as representing the Company’s views
as of any subsequent date. The Company specifically disclaims any
obligation to update any forward-looking statements included in
this press release.
Appendix: Glossary of Critical Terms Contained Herein
Affinity – Affinity is the strength of binding of a
molecule, such as a protein or antibody, to another molecule, such
as a ligand.
Avidity – Avidity is the accumulated strength of multiple
binding interactions.
Angiogenesis – Angiogenesis is the development,
formation, and maintenance of blood vessel structures. Without
sufficient blood flow, tissue may experience hypoxia (insufficient
oxygen) or lack of nutrition, which may cause cell death.i
Baseline – The condition of a patient at the start of the
clinical trial; a patient’s health status upon starting a clinical
trial prior to receiving therapy.
Cooperative binding – Cooperative binding occurs when the
number of binding sites on the molecule that can be occupied by a
specific ligand (e.g., protein) is impacted by the ligand’s
concentration. For example, this can be due to an affinity for the
ligand that depends on the amount of ligand bound or the binding
strength of the molecule to one ligand based on the concentration
of another ligand, increasing the chance of another ligand binding
to the compound.ii
Immunotherapy – Immunotherapy is a type of treatment,
including cancer treatments, that help a person’s immune system
fight cancer. Examples include anti-PD-1 therapies.iii
Intracranial – Within the cranium or skull.
PD-1 – Programmed cell
Death protein 1 is a protein on the surface of T cells and other
cells. PD-1 plays a key role in reducing the regulation of
ineffective or harmful immune responses and maintaining immune
tolerance. However, with respect to cancer tumor cells, PD-1 can
act as a stopping mechanism (a brake or checkpoint) by binding to
PD-L1 ligands that exist on tumor cells and preventing the T cells
from targeting cancerous tumor cells.iv
PD-L1 – Programmed cell
Death Ligand 1 is expressed
by cancerous tumor cells as an adaptive immune mechanism to escape
anti-tumor responses, thus believed to suppress the immune system’s
response to the presence of cancer cells. v
PD-L1 TPS – PD-L1 Tumor
Proportion Score represents the percentage of tumor cells
that express PD-L1 proteins.
PFS – Progression-Free
Survival.
RANO – Response Assessment in Neuro-Oncology, the
standard for assessing the response of a brain or spinal cord tumor
to therapy.
SQ-NSCLC – Non-small cell lung cancer tumors of squamous
histology.
T Cells – T cells are a type of white blood cell that is
a component of the immune system that, in general, fights against
infection and harmful cells like tumor cells.vi
Tetravalent – A tetravalent molecule has four binding
sites or regions.
Tumor Microenvironment – The tumor microenvironment is
the ecosystem that surrounds a tumor inside the body. It includes
immune cells, the extracellular matrix, blood vessels and other
cells, like fibroblasts. A tumor and its microenvironment
constantly interact and influence each other, either positively or
negatively.vii
VEGF – Vascular Endothelial Growth
Factor is a signaling protein that
promotes angiogenesis.viii
i Shibuya M. Vascular Endothelial Growth Factor (VEGF) and Its
Receptor (VEGFR) Signaling in Angiogenesis: A Crucial Target for
Anti- and Pro-Angiogenic Therapies. Genes Cancer. 2011
Dec;2(12):1097-105. ii Stefan MI, Le Novère N. Cooperative binding.
PLoS Comput Biol. 2013;9(6) iii US National Cancer Institute, a
part of the National Institute of Health (NIH).
https://www.cancer.gov/about-cancer/treatment/types/immunotherapy.
Accessed March 2024. iv Han Y, et al. PD-1/PD-L1 Pathway: Current
Researches in Cancer. Am J Cancer Res. 2020 Mar 1;10(3):727-742. v
Han Y, et al. PD-1/PD-L1 Pathway: Current Researches in Cancer. Am
J Cancer Res. 2020 Mar 1;10(3):727-742. vi Cleveland Clinic.
https://my.clevelandclinic.org/health/body/24630-t-cells. Accessed
March 2024. vii MD Anderson Cancer Center.
https://www.mdanderson.org/cancerwise/what-is-the-tumor-microenvironment-3-things-to-know.h00-159460056.html.
Accessed March 2024. viii Shibuya M. Vascular Endothelial Growth
Factor (VEGF) and Its Receptor (VEGFR) Signaling in Angiogenesis: A
Crucial Target for Anti- and Pro-Angiogenic Therapies. Genes
Cancer. 2011 Dec;2(12):1097-105.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20240322987758/en/
Contact Summit Investor Relations: Dave Gancarz Chief
Business & Strategy Officer Nathan LiaBraaten Senior Director,
Investor Relations investors@smmttx.com
Summit Therapeutics (NASDAQ:SMMT)
Historical Stock Chart
From Mar 2024 to Apr 2024
Summit Therapeutics (NASDAQ:SMMT)
Historical Stock Chart
From Apr 2023 to Apr 2024
