Two Oral Presentations Featured Updated
Ivonescimab Data from Phase II Studies in CRC and TNBC in Addition
to Poster Presentation on HNSCC
Encouraging Phase II Data Supports the
Continuing Expansion of the Clinical Development of Ivonescimab
Outside of Metastatic Non-Small Cell Lung Cancer
Summit Therapeutics Inc. (NASDAQ: SMMT) (“Summit,” “we,” or the
“Company”) today announced that data for the novel, potential
first-in-class investigational bispecific antibody, ivonescimab,
was presented at the 2024 European Society for Medical Oncology
Annual Meeting (ESMO 2024) in Barcelona, Spain, including two
presentations and one poster featuring updated ivonescimab data in
advanced triple-negative breast cancer (TNBC), recurrent /
metastatic head and neck squamous cell carcinoma (HNSCC), and
metastatic microsatellite-stable (MSS) colorectal cancer (CRC).
Each trial from which the data was generated was a Phase II study
conducted in China sponsored by Akeso Inc. (HKEX Code: 9926.HK)
with data generated and analyzed by Akeso.
Based on the results of these Phase II data sets as well as data
announced earlier in 2024, including early-stage non-small cell
lung cancer and biliary tract cancer, Summit intends to explore
further clinical development of ivonescimab in solid tumor settings
outside of metastatic non-small cell lung cancer, the Company’s
current area of focus in its Phase III clinical trials.
Metastatic MSS Colorectal Cancer
The first oral presentation was presented by Dr. Yanhong Deng,
Sun Yat-Sen University. The presentation was entitled, The efficacy
and safety of ivonescimab with or without ligufalimab in
combination with FOLFOXIRI (chemotherapy) as first-line treatment
for metastatic CRC, presenting the current data from AK112-206,
included data from this single-region (China), multicenter,
open-label, Phase II randomized study of patients with first-line
metastatic MSS CRC (NCT05382442).
The study was designed to assess patients who were randomly
assigned to receive ivonescimab plus FOLFOXIRI with or without
ligufalimab (anti-CD47 monoclonal antibody). Note that ligufalimab,
or AK117, is Akeso’s proprietary, investigational product that is
not approved by any regulatory authority, and to which Summit does
not have any license or ownership rights.
As of February 29, 2024, 22 patients received ivonescimab plus
FOLFOXIRI (“Group A” with median follow-up time of 9 months); 18
patients received ivonescimab plus ligufalimab plus FOLFOXIRI
(“Group B” with median follow-up time of 9.6 months).
Ivonescimab + Chemo
(Group A) (n = 22)
Ivonescimab + Ligufalimab +
Chemo (Group B) (n = 18)a
Overall response rate
81.8%
(95% CI: 59.7, 94.8)
88.2%
(95% CI: 63.6, 98.5)
Disease control rate
100%
(95% CI: 84.6, 100)
100%
(95% CI: 80.5, 100)
Median PFS
NR
NR
9-month PFS rate
81.4%
(95% CI: 52.1, 93.7)
86.2%
(95% CI: 55.0, 96.4)
Serious TRAE
22.7%
11.1%
TRAEs Leading to Permanent
Discontinuation
0
5.6%
a As of data cutoff, one patient in Group B had not yet had a
post-baseline tumor assessment; Group B response and control rates
based on n=17.
All patients in both Group A and Group B experienced a reduction
in their tumor burden compared to their baseline tumor assessment.
The overall response rate and the disease control rate for the 39
patients who had a least one post-baseline tumor assessment was
84.6% and 100%, respectively. Median progression-free survival was
not reached in either group at the time of this analysis.
The safety profile in this Phase II study was acceptable and
manageable. No patients receiving ivonescimab plus FOLFOXIRI and
one patient receiving ivonescimab plus ligufalimab plus FOLFOXIRI
permanently discontinued drug treatment due to treatment-related
adverse events. The most common TRAEs were anemia, proteinuria,
white blood cell count decreases, and neutrophil count decreases in
this Phase II data set.
Advanced Triple Negative Breast Cancer
The second oral presentation was presented by Dr. Xiaojia Wang,
Zhejiang Cancer Hospital. The presentation was entitled, The safety
and efficacy of ivonescimab in combination with chemotherapy as
first-line (1L) treatment for triple-negative breast cancer (TNBC),
presenting the current data from AK117-203, included data from this
single-region (China), multicenter, open-label, Phase II study
(NCT05227664).
The results presented were from the portion of the study
intended to assess patients who received ivonescimab plus
chemotherapy (either paclitaxel or nab-paclitaxel) with locally
advanced or metastatic TNBC.
As of May 31, 2024, 30 patients received ivonescimab plus
chemotherapy with median follow-up time of 10.2 months. Sixty
percent of patients had previously received taxane-based
chemotherapy in either the neoadjuvant or adjuvant setting in this
Phase II data set.
Overall
(n = 30)a
Overall response rate
72.4%
Disease control rate
100%
Median PFS
9.3 months
(95% CI: 6.24, NE)
Serious TRAE
30%
TRAEs Leading to Permanent
Discontinuation
0
PD-L1 CPS >10
(n = 6)
PD-L1 CPS <10
(n = 24)a
PD-L1 CPS <1
(n = 16)a
Overall response rate
83.3%
69.6%
86.7%
Disease control rate
100%
100%
100%
Median PFS
NR
(5.36, NE)
9.3 months
(5.55, NE)
9.3 months
(5.26, NE)
a As of data cutoff, one patient with a PD-L1 CPS expression of
0 had not yet had a post-baseline tumor assessment; Overall
patients, PD-L1 CPS <10, and PD-L1 CPS <1 response and
control rates based on n=29, n=23, and n=15, respectively.
All patients experienced a reduction in their tumor burden
compared to their baseline tumor assessment. The overall response
rate and the disease control rate for the 29 patients who had at
least one post-baseline tumor assessment were 72.4% and 100%,
respectively. Median progression-free survival was 9.30 months as
the time of this analysis.
The safety profile in this Phase II study was acceptable and
manageable. No patients receiving ivonescimab plus chemotherapy
permanently discontinued drug treatment due to treatment-related
adverse events. The most common TRAEs were white blood cell count
decreases, ALT increases, alopecia, AST increases, and neutrophil
count decreases in this Phase II data set.
Recurrent / Metastatic Head and Neck Squamous Cell
Carcinoma
The third data presentation was a poster from Dr. Xiaozhong
Chen, et al. The poster was entitled, Evaluation of the safety and
efficacy of ivonescimab in combination with ligufalimab (anti-CD47)
as first-line treatment for PD-L1 positive recurrent/metastasis
HNSCC, presenting current data from a portion of AK117-201. The
data is from a single-region (China), multicenter, open-label,
Phase II study (NCT05229497).
The results presented were from the portion of the study
intended to assess patients who received ivonescimab with or
without ligufalimab (anti-CD47) with PD-L1 positive, locally
advanced or metastatic recurrent / metastatic head and neck
squamous cell carcinoma.
As of March 19, 2024, 10 patients received ivonescimab (median
follow-up: 3.3 months) and 20 patients received ivonescimab plus
ligufalimab (median follow-up 4.1 months). Four of 10 patients
receiving ivonescimab had a PD-L1 CPS of 1-20; nine of 20 patients
administered ivonescimab plus ligufalimab had a PD-L1 CPS of 1-20;
the remaining patients in each arm had a PD-L1 CPS >20.
Ivonescimab
(n=10)
Ivonescimab +
Ligufalimab
(n = 20)
Overall response rate
30.0%
60.0%
Disease control rate
80.0%
90.0%
Median PFS
5.0 months
7.1 months
6-month PFS rate
NR
71.8%
Serious TRAE
0
5.0%
TRAEs Leading to Permanent
Discontinuation
0
0
The overall response rate and the disease control rate for the
30 patients was 50.0% and 86.7%, respectively.
The safety profile in this Phase II study was acceptable and
manageable. No patients receiving ivonescimab or ivonescimab plus
ligufalimab in this data set permanently discontinued drug
treatment due to treatment-related adverse events. The most common
TRAEs in this Phase II data set were proteinuria, dermatitis
acneiform (each observed in both arms), and hypothyroidism
(observed only in the ivonescimab plus ligufalimab arm).
About Ivonescimab
Ivonescimab, known as SMT112 in Summit’s license territories,
the United States, Canada, Europe, Japan, Latin America, including
Mexico and all countries in Central America, South America, and the
Caribbean, the Middle East, and Africa, and as AK112 in China and
Australia, is a novel, potential first-in-class investigational
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 unique
cooperative binding to each of its intended targets with multifold
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 TME 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,
together with a half-life of 6 to 7 days (Zhong, et al, SITC,
2023), is to improve upon previously established efficacy
thresholds, in addition to side effects and safety profiles
associated with these targets.
Ivonescimab was engineered by Akeso Inc. (HKEX Code: 9926.HK)
and is currently engaged in multiple Phase III clinical trials.
Over 1,800 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 multi-regional Phase III clinical trials, HARMONi and
HARMONi-3, with a plan to initiate HARMONi-7 in early 2025.
HARMONi is a Phase III clinical trial which intends to evaluate
ivonescimab combined with chemotherapy compared to placebo plus
chemotherapy in patients with EGFR-mutated, locally advanced or
metastatic non-squamous NSCLC who have progressed after treatment
with a 3rd generation EGFR TKI (e.g., osimertinib).
HARMONi-3 is a Phase III clinical trial which is designed to
evaluate ivonescimab combined with chemotherapy compared to
pembrolizumab combined with chemotherapy in patients with
first-line metastatic squamous NSCLC.
HARMONi-7 is a planned Phase III clinical trial which is
intended to evaluate ivonescimab monotherapy compared to
pembrolizumab monotherapy in patients with first-line metastatic
NSCLC whose tumors have high PD-L1 expression (PD-L1 TPS
> 50%).
In addition, Akeso has recently had positive read-outs in two
single-region (China), randomized Phase III clinical trials for
ivonescimab in NSCLC, HARMONi-A and HARMONi-2.
HARMONi-A was a Phase III clinical trial which evaluated
ivonescimab combined with chemotherapy compared to placebo plus
chemotherapy in patients with EGFR-mutated, locally advanced or
metastatic non-squamous NSCLC who have progressed after treatment
with an EGFR TKI.
HARMONi-2 is a Phase III clinical trial evaluating monotherapy
ivonescimab against monotherapy pembrolizumab in patients with
locally advanced or metastatic NSCLC whose tumors have positive
PD-L1 expression (PD-L1 TPS >1%).
Ivonescimab is an investigational therapy that is not approved
by any regulatory authority in Summit’s license territories,
including the United States and Europe. Ivonescimab was approved
for marketing authorization in China in May 2024.
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 @SMMT_TX.
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 intended use of the net
proceeds from the private placements, 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, statements about the previously disclosed
At-The-Market equity offering program (“ATM Program”), the expected
proceeds and uses thereof, 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
Company’s ability to sell shares of our common stock under the ATM
Program, the conditions affecting the capital markets, general
economic, industry, or political conditions, 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.1
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.2
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.3
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.4
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.5
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.6
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.7
VEGF – Vascular Endothelial Growth Factor is a signaling
protein that promotes angiogenesis.8
Summit Therapeutics and the Summit Therapeutics
logo are trademarks of Summit Therapeutics Inc. Copyright 2024,
Summit Therapeutics Inc. All Rights Reserved.
____________________ 1 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 2 Stefan MI, Le Novère N.
Cooperative binding. PLoS Comput Biol. 2013;9(6) 3 US National
Cancer Institute, a part of the National Institute of Health (NIH).
https://www.cancer.gov/about-cancer/treatment/types/immunotherapy.
Accessed April 2024. 4 Han Y, et al. PD-1/PD-L1 Pathway: Current
Researches in Cancer. Am J Cancer Res. 2020 Mar 1;10(3):727-742. 5
Han Y, et al. PD-1/PD-L1 Pathway: Current Researches in Cancer. Am
J Cancer Res. 2020 Mar 1;10(3):727-742. 6 Cleveland Clinic.
https://my.clevelandclinic.org/health/body/24630-t-cells. Accessed
April 2024. 7 MD Anderson Cancer Center.
https://www.mdanderson.org/cancerwise/what-is-the-tumor-microenvironment-3-things-to-know.h00-159460056.html.
Accessed April 2024. 8 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/20240916841138/en/
Contact Summit Investor Relations: Dave Gancarz Chief
Business & Strategy Officer
Nathan LiaBraaten Senior Director, Investor Relations
investors@smmttx.com
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