Separate & Distinct from HARMONi-2
Announcement, HARMONi-A Showed Clinically Meaningful and
Statistically Significant Benefit: PFS Hazard Ratio of 0.46
For Subset of Patients Previously Receiving 3rd
Generation EGFR-TKI: PFS Hazard Ratio of 0.48
5.6% Treatment Discontinuation of Ivonescimab
due to Adverse Events vs. 2.5% Treatment Discontinuation of
Placebo
HARMONi-A was Featured in Oral Presentation at
ASCO 2024 on May 31, 2024
Conference Call to be Held at 8:00am ET on
Monday, June 3, 2024
Summit Therapeutics Inc. (NASDAQ: SMMT) (“Summit,” “we,” or the
“Company”) announced that, on May 24, 2024, our partner, Akeso Inc.
(Akeso, HKEX Code: 9926.HK), received marketing authorization in
China from the National Medical Products Administration (NMPA). The
approval is based on the positive dataset associated with
HARMONi-A, a single region, multi-center, Phase III study conducted
in China sponsored by Akeso with data generated and analyzed by
Akeso.
HARMONi-A evaluated ivonescimab combined with platinum-doublet
chemotherapy in patients with epidermal growth factor receptor
(EGFR)-mutated, locally advanced or metastatic non-squamous
non-small cell lung cancer (NSCLC) who have progressed after
treatment with an EGFR tyrosine kinase inhibitor (TKI) against
placebo plus platinum-doublet chemotherapy. This is a clinical
setting with a patient population where PD-1 monoclonal antibodies
have previously been unsuccessful in Phase III global clinical
trials. The Phase III HARMONi-A study provides further evidence
supporting the differentiated mechanism of action of ivonescimab, a
PD-1 / VEGF bispecific antibody evidencing cooperative binding
characteristics.
This data and trial are separate and distinct from the Phase III
HARMONi-2 trial in locally advanced or metastatic NSCLC whose
tumors have positive PD-L1 expression (PD-L1 TPS >1%), which was
covered in a separate announcement. For clarity, the data in this
release is with respect to the HARMONi-A trial.
Clinically Meaningful Efficacy
Progression free survival (PFS), the primary endpoint of the
study, was significantly improved in the ivonescimab plus
chemotherapy arm (HR 0.46; 95% CI: 0.34 – 0.62; p<0.001),
representing a 54% reduction in the risk of disease progression
compared to chemotherapy. Median PFS for ivonescimab plus
chemotherapy was 7.1 months (95% CI: 5.9 – 8.7), as compared to 4.8
months (95% CI: 4.2 – 5.6) for placebo plus chemotherapy. In
addition, for the subgroup of patients receiving a 3rd generation
TKI (e.g., osimertinib or other locally approved 3rd generation
TKIs), patients experienced a reduced risk of disease progression
of 52% (HR: 0.48; 95% CI: 0.35 – 0.66). The PFS benefit was
demonstrated across all clinical subgroups.
While not yet mature, overall survival (OS) analyses performed
on request of the NMPA trended positively for ivonescimab plus
chemotherapy vs. chemotherapy alone: after 10.2 months of median
follow-up, the hazard ratio (HR) was 0.72 (95% CI: 0.48 – 1.09). An
additional analysis performed after approximately 17.6 months of
median follow-up showed a hazard ratio of 0.80 (95% CI: 0.59 –
1.08). Both overall survival curves appear to demonstrate clear
separation between the two arms of the trial and show a trend in
improvement of survival towards ivonescimab plus chemotherapy.
Overall response rate (ORR) was 50.6% (95% CI: 42.6% – 58.6%)
for those receiving ivonescimab plus chemotherapy vs. 35.4% (95%
CI: 28.0% - 43.3%) for those receiving chemotherapy alone.
Ivonescimab plus chemotherapy usage resulted in a disease control
rate (DCR) – those who either responded or were considered to have
stable disease under RECIST 1.1 criteria – of 93.1% (95% CI: 88.0%
- 96.5%) vs. 83.2% (95% CI: 76.5% - 88.6%) for those receiving
placebo plus chemotherapy.
HARMONi-A (n=322)
Ivonescimab + Chemo
(n=161)
Placebo + Chemo
(n=161)
Median PFS
7.1 months
(95% CI: 5.9 – 8.7)
4.8 months
(95% CI: 4.2 – 5.6)
PFS HR
0.46
(95% CI: 0.34 – 0.62)
ORR
50.6%
(95% CI: 42.6% – 58.6%)
35.4%
(95% CI: 28.0% – 43.3%)
DCR
93.1%
(95% CI: 88.0% – 96.5%)
83.2%
(95% CI: 76.5% – 88.6%)
Median OS (at 10.2 months mFU)
Not reached
(95% CI: 14.3 – NE)
14.3 months
(95% CI: 11.2 – NE)
OS HR (10.2 months mFU)
0.72
(95% CI: 0.48 – 1.09)
Median OS (at 17.6 months mFU)
17.1 months
(95% CI: 14.6 – NE)
14.5 months
(95% CI: 12.8 – 18.1)
OS HR (17.6 months mFU)
0.80
(95% CI: 0.59 – 1.08)
mFU = median follow-up; NE = not estimable; mFU is 7.89 months
unless otherwise noted above
Manageable Safety Profile
Ivonescimab demonstrated an acceptable and manageable safety
profile. The most common treatment related adverse events (TRAEs),
both all grades and Grade 3 or higher, were hematological,
laboratory count-based events: white blood cell count decreases,
anemia, neutrophil count decreases, and platelet count decreases.
There were nine patients (5.6%) who discontinued ivonescimab due to
TRAEs compared to four patients (2.5%) who discontinued placebo due
to TRAEs. Grade 3 or higher immune-related adverse events occurred
in 6.2% of patients receiving ivonescimab plus chemotherapy and
2.5% of patients receiving placebo plus chemotherapy. Grade 3 or
higher VEGF-related adverse events between the two arms were
similar (3.1% vs. 2.5%, respectively); there were no Grade 3
bleeding or arterial thrombotic events in the ivonescimab plus
chemotherapy arm. No TRAEs resulted in the death of a patient in
either arm in this Phase III study.
HARMONi-A (n=322)
Ivonescimab + Chemo
(n=161)
Placebo + Chemo
(n=161)
TRAE Gr 3+
54.0%
42.9%
TRAE Gr 3+ Immune-related
6.2%
2.5%
TRAE Gr 3+ VEGF-related
3.1%
2.5%
Gr 3+ TRAEs with >10% Incidence:
Gr 3+ WBC Count Decrease
19.9%
16.8%
Gr 3+ Anemia
13.7%
12.4%
Gr 3+ Neutrophil Count Decrease
29.8%
19.3%
Gr 3+ Platelet Count Decrease
16.1%
11.8%
“After yesterday’s announcement regarding the HARMONi-2 trial,
these results from HARMONi-A – including its strong efficacy,
across subgroups, and its differentiated, manageable safety profile
– and the associated approval of ivonescimab in China further
validates the benefits that ivonescimab has the potential to bring
to patients around the globe,” stated Robert W. Duggan, Chairman
and Chief Executive Officer of Summit.
“We are excited to continue to develop ivonescimab with
appropriate, accelerated pace and with the intent to make a
significant difference for those patients who may benefit most from
new, innovative therapies in lung cancer and other solid tumors,”
added Dr. Maky Zanganeh, Chief Executive Officer and President of
Summit.
Summit Therapeutics continues to enroll in the HARMONi clinical
trial, a multi-regional Phase III study evaluating ivonescimab plus
platinum-doublet chemotherapy vs. placebo plus platinum-doublet
chemotherapy with EGFR-mutated, locally advanced or metastatic
non-squamous NSCLC who have progressed after treatment with a 3rd
generation EGFR TKI. HARMONi will analyze patients enrolled in
North America, China, and Europe. HARMONi intends to include all
patients from the HARMONi-A trial who previously received a 3rd
generation TKI – representing approximately 276 patients (85%) of
the HARMONi-A trial. The planned total enrollment for the Phase III
multi-regional HARMONi trial is approximately 420 patients, which
Summit intends to complete enrolling during the second half of
2024.
HARMONi-A data was presented by Dr. Li Zhang, Sun Yat-Sen
University Cancer Center, at the 2024 American Society of Clinical
Oncology (ASCO) Annual Meeting in Chicago, IL.
In addition to the HARMONi-A oral presentation, there will be a
poster featuring Phase II clinical trial data for ivonescimab in
combination with chemotherapy in front-line biliary tract cancer
presented on Saturday, June 1, 2024.
Conference Call
Summit Therapeutics Inc. will host a conference call to discuss
recent updates related to ivonescimab, including data released at
ASCO, on Monday June 3, 2024, before the market opens.
Summit will host a live webcast of the conference call at 8:00am
ET, which will be accessible through our website www.smmttx.com,
and can also be accessed via the following link:
https://events.q4inc.com/attendee/130822402.
The dial-in information for US attendees is toll-free at (800)
715-9871. Additionally, all attendees may access through the toll
number, (646) 307-1963. The Conference ID is 4259251.
An archived edition of the webcast will be available on our
website later in the day on Monday.
About the ASCO 2024 Data
Presentation Title: Ivonescimab combined with chemotherapy in
patients with EGFR-mutant non-squamous NSCLC who progressed on EGFR
TKI treatment (HARMONi-A): A randomized, double-blind,
multi-center, phase 3 trial
ASCO Abstract No.: 8508
Session Date & Time: Friday, May 31 at 4:57pm CT
Poster Title: The safety and efficacy of ivonescimab in
combination with chemotherapy as first-line treatment for advanced
biliary tract cancer
ASCO Abstract No.: 4095
Session Date & Time: Saturday, June 1 at 1:30pm CT
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 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 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.1 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,1 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, HARMONi and
HARMONi-3.
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.
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 Lung Cancer
Lung cancer is believed to impact approximately 600,000 people
across the United States, United Kingdom, Spain, France, Italy,
Germany, and Japan.2 NSCLC is the most prevalent type of lung
cancer and represents approximately 80% to 85% of all incidences.3
Among patients with non-squamous NSCLC, approximately 15% have
EGFR-sensitizing mutations in the United States and Europe.4
Patients with squamous histology represent approximately 25% to 30%
of NSCLC patients.5
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, statements about the previously disclosed
At-The-Market equity offering program (“ATM Program”), the expected
use 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.6
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.7
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.8
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.9
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.10
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.11
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.12
VEGF – Vascular Endothelial Growth Factor is a signaling
protein that promotes angiogenesis.13
___________ 1 Zhong, et al, SITC 2023 2 American Cancer Society:
www.cancer.org/cancer/types/lung-cancer/about/key-statistics.html.
Accessed April 2024; World Health Organization: International
Agency for Research on Cancer, Globocan data by country (UK, Spain,
France, Italy, Germany); Japan National Cancer Registry. 3 Schabath
MB, Cote ML. Cancer Progress and Priorities: Lung Cancer. Cancer
Epidemiology, Biomarkers & Prevention. (2019). 4 About
EGFR-Positive Lung Cancer | Navigating EGFR (lungevity.org). 5
Schabath MB, Cote ML. Cancer Progress and Priorities: Lung Cancer.
Cancer Epidemiology, Biomarkers & Prevention. (2019). 6 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 7
Stefan MI, Le Novère N. Cooperative binding. PLoS Comput Biol.
2013;9(6) 8 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. 9 Han Y, et al. PD-1/PD-L1 Pathway: Current
Researches in Cancer. Am J Cancer Res. 2020 Mar 1;10(3):727-742. 10
Han Y, et al. PD-1/PD-L1 Pathway: Current Researches in Cancer. Am
J Cancer Res. 2020 Mar 1;10(3):727-742. 11 Cleveland Clinic.
https://my.clevelandclinic.org/health/body/24630-t-cells. Accessed
April 2024. 12 MD Anderson Cancer Center.
https://www.mdanderson.org/cancerwise/what-is-the-tumor-microenvironment-3-things-to-know.h00-159460056.html.
Accessed April 2024. 13 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/20240531688842/en/
Contact Summit Investor Relations: Dave Gancarz Chief
Business & Strategy Officer
Nathan LiaBraaten Senior Director, Investor Relations
investors@smmttx.com
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