- Objective response rate of 54.8% seen with Daiichi Sankyo and
Merck’s ifinatamab deruxtecan at 12 mg/kg dose in pretreated
patients
- 12 mg/kg selected as optimal dose for extension part of
IDeate-Lung01 phase 2 trial and recently initiated IDeate-Lung02
phase 3 study
Results from an interim analysis of the dose-optimization part
of the ongoing IDeate-Lung01 phase 2 trial showed ifinatamab
deruxtecan (I-DXd) continues to demonstrate promising objective
response rates in patients with pretreated extensive-stage small
cell lung cancer (ES-SCLC). These data were featured today as part
of a press conference and will be presented during an oral
presentation (OA04.03) on Sunday at the 2024 World Conference on
Lung Cancer (#WCLC24) hosted by the International Association for
the Study of Lung Cancer.
Ifinatamab deruxtecan is a specifically engineered, potential
first-in-class B7-H3 directed antibody drug conjugate (ADC)
discovered by Daiichi Sankyo (TSE: 4568) and being jointly
developed by Daiichi Sankyo and Merck (NYSE: MRK), known as MSD
outside of the United States and Canada.
Small cell lung cancer (SCLC) is the second most common type of
lung cancer, accounting for about 15% of cases.1 SCLC is aggressive
and progresses rapidly to the metastatic stage, which has a
five-year survival rate of only 3%.2,3 Approximately 65% of all
SCLC tumors have a moderate-to-high expression of the protein
B7-H3, which is associated with disease progression and poor
prognosis.4,5
“Most patients treated for small cell lung cancer experience
rapid progression of disease and there is a high unmet need in the
advanced setting,” said Charles M. Rudin, MD, PhD, Deputy Director
of Memorial Sloan Kettering Cancer Center and Co-Director of the
Fiona and Stanley Druckenmiller Center for Lung Cancer Research.
“These interim results from the first part of the IDeate-Lung01
trial suggest that ifinatamab deruxtecan could play an important
role in treating patients with pretreated extensive-stage small
cell lung cancer and further research is warranted.”
A confirmed objective response rate (ORR) of 54.8% (95% CI:
38.7-70.2) and 26.1% (95% CI: 14.3-41.1) were observed in patients
with ES-SCLC receiving ifinatamab deruxtecan in the 12 mg/kg (n=42)
and 8 mg/kg (n=46) cohorts, respectively, as assessed by blinded
independent central review (BICR). Twenty-three partial responses
(PR) were seen in the 12 mg/kg cohort. One complete response (CR)
and eleven PRs were seen in the 8 mg/kg cohort. A median duration
of response (DoR) of 4.2 months (95% CI: 3.5-7.0) and 7.9 months
(95% CI: 4.1-NE) and a disease control rate (DCR) of 90.5% (95% CI:
77.4-97.3) and 80.4% (95% CI: 66.1-90.6) were observed in the 12
mg/kg and 8 mg/kg cohorts, respectively. The median duration of
treatment was 4.7 months for the 12 mg/kg dose (range, 0.03-15.2)
and 3.5 months for the 8 mg/kg dose (range, 0.03–13.9). Median
progression-free survival (PFS) of 5.5 months (95% CI: 4.2-6.7) and
4.2 months (95% CI: 2.8-5.6) and median overall survival (OS) of
11.8 months (95% CI: 8.9-15.3) and 9.4 months (95% CI: 7.8-15.9)
were observed in the 12 mg/kg and 8 mg/kg cohorts, respectively.
The 12 mg/kg dose has been selected for the dose expansion part of
the trial. Median follow-up was 15.3 months (95% CI: 13.6-16.2) in
the 12 mg/kg cohort and 14.6 months (95% CI: 13.4-16.5) in the 8
mg/kg cohort as of data cutoff of April 25, 2024.
In a subset of patients with brain target lesions at baseline,
an intracranial ORR of 50.0% (95% CI: 18.7-81.3) and 66.7% (95% CI:
22.3-95.7) were observed as assessed by central nervous system
(CNS) BICR in the 12 mg/kg (n=10) and 8 mg/kg (n=6) cohorts,
respectively. In these patients, two intracranial CRs were seen in
each cohort. Three and two intracranial PRs and five and two cases
of stable disease (SD) were seen in the 12 mg/kg and 8 mg/kg
cohorts, respectively.
“The objective response rate and median overall survival of
nearly a year along with the preliminary intracranial responses
observed reinforces the potential for ifinatamab deruxtecan to
improve outcomes for patients living with this difficult-to-treat
type of lung cancer,” said Mark Rutstein, MD, Global Head, Oncology
Clinical Development, Daiichi Sankyo. “We look forward to seeing
additional results from the extension part of the IDeate-Lung01
phase 2 trial and the recently initiated IDeate-Lung02 phase 3
trial where we are evaluating ifinatamab deruxtecan in patients
with extensive-stage small cell lung cancer versus treatment of
physician’s choice of chemotherapy.”
“These results demonstrate promising objective response rates in
patients with pre-treated extensive-stage small cell lung cancer, a
patient population with a poor prognosis and limited treatment
options,” said Marjorie Green, MD, Senior Vice President and Head
of Oncology, Global Clinical Development, Merck Research
Laboratories. “We are encouraged by these results supporting the
potential of B7-H3 as an actionable target in small cell lung
cancer and look forward to advancing our pivotal clinical
development program for ifinatamab deruxtecan.”
The safety profile seen in IDeate-Lung01 is consistent with that
observed for ifinatamab deruxtecan in previous trials with no new
safety signals identified. Grade 3 or higher treatment-emergent
adverse events (TEAEs) occurred in 50.0% and 43.5% of patients in
the 12 mg/kg (n=42) and 8 mg/kg (n=46) cohorts, respectively. The
most common treatment-related TEAEs (>20% of total population)
across both doses include nausea (50.0% and 28.3%), decreased
appetite (42.9% and 17.4%), anemia (35.7% and 13.0%), decreased
neutrophil count/neutropenia (33.3% and 10.9%), white blood cell
decreased (21.4% and 4.3%) and asthenia (1.4% and 13.0%). Five
(11.9%) and four (8.7%) interstitial lung disease (ILD)/pneumonitis
events were confirmed as treatment-related in the 12 mg/kg and 8
mg/kg doses, respectively, as determined by an independent
adjudication committee. The majority of ILD events (four with 12
mg/kg, three with 8 mg/kg) were low grade (grade 1 or 2). There was
one grade 3 (12 mg/kg) and one grade 5 (8 mg/kg) ILD. No ILD events
were pending adjudication at the time of data cutoff of April 25,
2024. Treatment discontinuations due to adverse events occurred in
16.7% and 6.5% in the 12 mg/kg and 8 mg/kg cohorts,
respectively.
Patients in IDeate-Lung01 receiving ifinatamab deruxtecan
received a median of two lines of therapy in both dose groups
including a majority (76.1%) previously treated with immunotherapy.
The median treatment duration was 4.7 months (range: 0.03-15.2) in
the 12 mg/kg cohort and 3.5 months (range: 0.03-13.9) in the 8mg/kg
cohort.
Summary of IDeate-Lung01 Results
Efficacy Measure
Ifinatamab deruxtecan
(12 mg/kg)
n=42
Ifinatamab deruxtecan
(8 mg/kg)
n=46
Confirmed ORR, % (95% CI)
54.8% (38.7-70.2)
26.1% (14.3-41.1)
CR, n (%)
0
1 (2.2%)
PR, n (%)
23 (54.8%)
11 (23.9%)
Stable disease (SD)/non-CR/non-PD, n
(%)
15 (35.7%)
25 (54.3%)
Progressive disease (PD), n (%)
2 (4.8%)
5 (10.9%)
DCR, % (95% CI)
90.5% (77.4-97.3)
80.4% (66.1-90.6)
DoR, median (95% CI), months
4.2 months (3.5-7.0)
7.9 months (4.1-NE)
TTR, median (95% CI), months
1.4 months (1.0-8.1)
1.4 months (1.2-1.5)
PFS, median (95% CI), months
5.5 months (4.2-6.7)
4.2 months (2.8-5.6)
OS, median (95% CI), months
11.8 months (8.9-15.3)
9.4 months (7.8-15.9)
CR, complete response; DCR, disease control rate; DoR, duration
of response; ORR, objective response rate; OS, overall survival,
PR, partial response; PD, progressive disease; PFS,
progression-free survival; TTR, time to response; SD, stable
disease
About the IDeate-Lung01 Trial IDeate-Lung01 is a global,
multicenter, randomized, open-label two-part phase 2 trial
evaluating the safety and efficacy of ifinatamab deruxtecan in
patients with ES-SCLC. In the first part of the trial (dose
optimization), patients were previously treated with at least one
prior line of platinum-based chemotherapy and a maximum of three
prior lines of therapy. In the second part (extension), patients
were previously treated with a minimum of two previous lines of
systemic therapy.
In the first part of the trial, patients were randomized 1:1 to
receive either 8 mg/kg or 12 mg/kg of ifinatamab deruxtecan. In the
second part of the trial, patients will receive the recommended
dose for expansion (12 mg/kg) of ifinatamab deruxtecan.
The primary endpoint is ORR as assessed by BICR. Secondary
endpoints include DoR, PFS, OS, DCR, time to response and overall
safety profile. Intracranial ORR was assessed by BICR as an
exploratory analysis.
IDeate-Lung01 is enrolling patients in Asia, Europe and North
America. For more information about the trial, visit
ClinicalTrials.gov.
About Small Cell Lung Cancer More than 2.48 million lung
cancer cases were diagnosed globally in 2022.6 SCLC is the second
most common type of lung cancer, accounting for approximately 15%
of cases.1 SCLC is aggressive and progresses rapidly to the
metastatic stage, which has a five-year survival rate of only
3%.2,3 While conventional first-line therapy for patients with
advanced SCLC may help some patients live longer, the current
second-line standard of care offers limited clinical benefit and
new treatment approaches are needed.7,8,9,10
About B7-H3 B7-H3 is a transmembrane protein that belongs
to the B7 family of proteins which bind to the CD28 family of
receptors that includes PD-1.11,12 B7-H3 is overexpressed in a wide
range of cancer types, including SCLC, and its overexpression has
been shown to correlate with poor prognosis, making B7-H3 a
promising therapeutic target.4,12,13,14,15 There are currently no
B7-H3 directed medicines approved for the treatment of any
cancer.
About Ifinatamab Deruxtecan Ifinatamab deruxtecan (I-DXd)
is an investigational potential first-in-class B7-H3 directed ADC.
Designed using Daiichi Sankyo’s proprietary DXd ADC Technology,
ifinatamab deruxtecan is comprised of a humanized anti-B7-H3 IgG1
monoclonal antibody attached to a number of topoisomerase I
inhibitor payloads (an exatecan derivative, DXd) via
tetrapeptide-based cleavable linkers.
Ifinatamab deruxtecan is being evaluated in a global development
program, which includes IDeate-Lung01, a phase 2 monotherapy trial
in patients with previously treated ES-SCLC; IDeate-Lung02, a phase
3 trial in patients with relapsed SCLC versus investigator’s choice
of chemotherapy; IDeate-Lung03, a phase 1b/2 trial in patients with
ES-SCLC in combination with atezolizumab with or without
carboplatin as first-line induction or maintenance therapy;
IDeate-PanTumor01, a phase 1/2 first-in-human trial in patients
with advanced solid malignant tumors in collaboration with Sarah
Cannon Research Institute (SCRI) with study operational oversight
and delivery provided through SCRI’s early phase oncology clinical
research organization, SCRI Development Innovations in Nashville,
TN; and, IDeate-PanTumor02, a phase 2 trial in patients with
recurrent or metastatic solid tumors.
Ifinatamab deruxtecan was granted orphan drug designation by the
U.S. Food and Drug Administration in April 2023 and by the European
Commission in February 2024 for the treatment of SCLC.
About the Daiichi Sankyo and Merck Collaboration Daiichi
Sankyo and Merck entered into a global collaboration in October
2023 to jointly develop and commercialize patritumab deruxtecan
(HER3-DXd), ifinatamab deruxtecan (I-DXd) and raludotatug
deruxtecan (R-DXd), except in Japan where Daiichi Sankyo will
maintain exclusive rights. Daiichi Sankyo will be solely
responsible for manufacturing and supply. In August 2024, the
global co-development and co-commercialization agreement was
expanded to include MK-6070, an investigational delta-like ligand 3
(DLL3) targeting T-cell engager, which they will jointly develop
and commercialize worldwide, except in Japan where Merck will
maintain exclusive rights. Merck will be solely responsible for
manufacturing and supply for MK-6070.
About the ADC Portfolio of Daiichi Sankyo The Daiichi
Sankyo ADC portfolio consists of seven ADCs in clinical development
crafted from two distinct ADC technology platforms discovered
in-house by Daiichi Sankyo.
The ADC platform furthest in clinical development is Daiichi
Sankyo’s DXd ADC Technology where each ADC consists of a monoclonal
antibody attached to a number of topoisomerase I inhibitor payloads
(an exatecan derivative, DXd) via tetrapeptide-based cleavable
linkers. The DXd ADC portfolio currently consists of ENHERTU, a
HER2 directed ADC, and datopotamab deruxtecan (Dato-DXd), a TROP2
directed ADC, which are being jointly developed and commercialized
globally with AstraZeneca. Patritumab deruxtecan (HER3-DXd), a HER3
directed ADC, ifinatamab deruxtecan (I-DXd), a B7-H3 directed ADC,
and raludotatug deruxtecan (R-DXd), a CDH6 directed ADC, are being
jointly developed and commercialized globally with Merck. DS-3939,
a TA-MUC1 directed ADC, is being developed by Daiichi Sankyo.
The second Daiichi Sankyo ADC platform consists of a monoclonal
antibody attached to a modified pyrrolobenzodiazepine (PBD)
payload. DS-9606, a CLDN6 directed PBD ADC, is the first of several
planned ADCs in clinical development utilizing this platform.
Datopotamab deruxtecan, ifinatamab deruxtecan, patritumab
deruxtecan, raludotatug deruxtecan, DS-3939 and DS-9606 are
investigational medicines that have not been approved for any
indication in any country. Safety and efficacy have not been
established.
About Daiichi Sankyo Daiichi Sankyo is an innovative
global healthcare company contributing to the sustainable
development of society that discovers, develops and delivers new
standards of care to enrich the quality of life around the world.
With more than 120 years of experience, Daiichi Sankyo leverages
its world-class science and technology to create new modalities and
innovative medicines for people with cancer, cardiovascular and
other diseases with high unmet medical needs. For more information,
please visit www.daiichisankyo.com.
Merck’s Focus on Cancer Every day, we follow the science
as we work to discover innovations that can help patients, no
matter what stage of cancer they have. As a leading oncology
company, we are pursuing research where scientific opportunity and
medical need converge, underpinned by our diverse pipeline of more
than 25 novel mechanisms. With one of the largest clinical
development programs across more than 30 tumor types, we strive to
advance breakthrough science that will shape the future of
oncology. By addressing barriers to clinical trial participation,
screening and treatment, we work with urgency to reduce disparities
and help ensure patients have access to high-quality cancer care.
Our unwavering commitment is what will bring us closer to our goal
of bringing life to more patients with cancer. For more
information, visit https://www.merck.com/research/oncology/.
About Merck At Merck, known as MSD outside of the United States
and Canada, we are unified around our purpose: We use the power of
leading-edge science to save and improve lives around the world.
For more than 130 years, we have brought hope to humanity through
the development of important medicines and vaccines. We aspire to
be the premier research-intensive biopharmaceutical company in the
world – and today, we are at the forefront of research to deliver
innovative health solutions that advance the prevention and
treatment of diseases in people and animals. We foster a diverse
and inclusive global workforce and operate responsibly every day to
enable a safe, sustainable and healthy future for all people and
communities. For more information, visit www.merck.com and connect
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Forward-Looking Statement of Merck & Co., Inc., Rahway,
N.J., USA This news release of Merck & Co., Inc., Rahway,
N.J., USA (the “company”) includes “forward-looking statements”
within the meaning of the safe harbor provisions of the U.S.
Private Securities Litigation Reform Act of 1995. These statements
are based upon the current beliefs and expectations of the
company’s management and are subject to significant risks and
uncertainties. There can be no guarantees with respect to pipeline
candidates that the candidates will receive the necessary
regulatory approvals or that they will prove to be commercially
successful. If underlying assumptions prove inaccurate or risks or
uncertainties materialize, actual results may differ materially
from those set forth in the forward-looking statements.
Risks and uncertainties include but are not limited to, general
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including interest rate and currency exchange rate fluctuations;
the impact of pharmaceutical industry regulation and health care
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The company undertakes no obligation to publicly update any
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References: 1 Schabath MB, et al. Cancer Epidemiol Biomarkers
Prev. 2019 Oct;28(10):1563-1579. 2 Rudin CM, et al. Nat Rev Dis
Primers. 2021;7(1):3. 3 Cancer.net. Lung Cancer - Small Cell:
Statistics. Accessed August 2024. 4 Qiu M-j, et al. Front. Oncol.
2021;11:600238. 5 Dong P, et al. Front Oncol. 2018;8:264 6 World
Health Organization. International Agency for Research on Cancer.
U.S. Cancer Fact Sheet. Accessed August 2024. 7 American Cancer
Society. Treatment Choices for Small Cell Lung Cancer, by Stage.
Accessed August 2024. 8 Liu SV, et al. J Clin Oncol.
2021;39(6):619-30. 9 Paz-Ares L, et al. ESMO Open.
2022;7(2):100408. 10 von Pawel J, et al. J Clin Oncol. 2014;
32:4012-4019. 11 Zhao B, et al. J Hematol Oncol. 2022;15(1):153. 12
Janakiram M, et al. Immunol Rev. 2017;276(1):26-39. 13 Picarda E,
et al. Clin Cancer Res. 2016;22(14):3425-3431. 14 Bendell JC, et
al. J Clin Oncol. 2020;39(15 suppl 1). Abstract TPS3646. 15 Kontos
F, et al. Clin Cancer Res. 2021;27(5):1227-1235.
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Media Contacts:
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(908) 900-3183 jennifer.brennan@daiichisankyo.com
Japan Media: DS-PR@daiichisankyo.co.jp
Investor Relations Contact:
DaiichiSankyoIR@daiichisankyo.co.jp
Merck Media: Julie Cunningham (617) 519-6264
julie.cunningham@merck.com
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Investors: Peter Dannenbaum (732) 594-1579
peter.dannenbaum@merck.com
Damini Chokshi (732) 594-1577 damini_chokshi@merck.com
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