DARMSTADT, Germany - Friday, 24. May 2024
First-in-human data for potential first-in-class anti-CEACAM5 ADC with
topoisomerase 1 inhibitor payload, M9140, in treatment of metastatic
colorectal cancer to be featured in oral presentation
Phase I
data for tuvusertib, lead asset from the company’s unique portfolio of
DDR inhibitors, including an oral presentation on the combination with a
PARP inhibitor, support further clinical development
New
analyses contribute to totality of evidence supporting BAVENCIO
first-line maintenance as a standard-of-care in advanced bladder cancer
Not intended for Canada-, UK- or US-based media
(BUSINESS
WIRE)--Merck, a leading science and technology company, today announced
new research from the company’s diverse oncology portfolio will be
presented at the 2024 American Society of Clinical Oncology (ASCO)
Annual Meeting, May 31 to June 4, Chicago. Data from company- and
investigator-sponsored studies include 31 accepted abstracts across more
than 10 tumor types, including seven oral presentations, highlighting
the company’s innovative oncology pipeline encompassing potential
first-in-class approaches designed to hit cancer at its core.
“Our
research at the 2024 ASCO Annual Meeting showcases the advancement of
our novel pipeline designed to exploit the major vulnerabilities of
cancer, with new data from our lead investigational antibody-drug
conjugate and our DNA damage response portfolio,” said Victoria
Zazulina, M.D., Head of Development Unit, Oncology, for the Healthcare
business of Merck. “In addition, new analyses from pivotal studies and
collaborations underline our determination to maximize the impact of our
standard-of-care treatments as we seek to improve the lives of those
living with cancer.”
Highlights of the company’s data include:
First-in-human
data for the antibody-drug conjugate (ADC) M9140 (Abstract 3000). This
Phase I trial is investigating the safety, tolerability,
pharmacokinetics (PK), and preliminary clinical activity of M9140, the
company’s investigational ADC against carcinoembryonic antigen-related
cell adhesion molecule 5 (CEACAM5) with a novel exatecan payload, in
heavily pretreated patients with metastatic colorectal cancer. Data from
40 patients treated across seven dose levels in Part 1A of the study
showed encouraging clinical activity and a manageable and predictable
safety profile in this population. The randomized dose-expansion part of
the study is ongoing.
New findings for tuvusertib, the lead oral
ATRi asset from the company’s portfolio of DNA damage response (DDR)
inhibitors (Abstracts 3018, 2612, 2614). Data from the DDRiver™ Clinical
Trials program highlight the potential of the investigational oral
ataxia telangiectasia and RAD3-related inhibitor (ATRi) tuvusertib in
various combinations across solid tumors.
Part B1 of the
Phase I DDRiver Solid Tumors 301 study assessed safety as well as PK,
pharmacodynamics, and preliminary efficacy of different dosing regimens
of tuvusertib in combination with the poly-ADP ribose polymerase (PARP)
inhibitor niraparib in patients with locally advanced or metastatic
unresectable solid tumors refractory to standard treatment. Data show a
manageable safety profile and preliminary efficacy in patients with
advanced solid tumors, confirming suitability of this combination for
further evaluation.
Presentations from the Phase Ib DDRiver Solid
Tumors 320 study showcase further data on the combination of tuvusertib
with the company’s ataxia telangiectasia-mutated (ATM) inhibitor
lartesertib, building on the safety and efficacy data presented at the
AACR Annual Meeting in April 2024, and for the first time, with the
company’s immune checkpoint inhibitor BAVENCIO® (avelumab). The findings
further support that both DDRi assets are well-positioned for
combination development building on in-house expertise.
Post-hoc
independent read confirmation of Phase II efficacy data for xevinapant
(Abstract e18039). A previously published Phase II study of the
investigational oral IAP (inhibitor of apoptosis protein) inhibitor
xevinapant plus chemoradiotherapy (CRT) versus placebo plus CRT in
patients with unresected locally advanced squamous cell carcinoma of the
head and neck (LA SCCHN) showed improved efficacy outcomes. This
post-hoc analysis showed consistent outcomes when comparing the review
of selected efficacy endpoints by blinded independent review committee
(BIRC) with previously reported outcomes by investigator review.
Xevinapant plus CRT demonstrated a 62% reduction in the risk of disease
progression (by BIRC) or death compared with placebo plus CRT, with
prolonged duration of response and increased complete response rates.
Long-term
efficacy and safety analyses from JAVELIN Bladder 100 (Abstracts 4566,
4567). New analyses of this Phase III study, which has previously shown
in a post-hoc exploratory analysis a median overall survival of 29.7
months in patients who received BAVENCIO plus best supportive care (BSC)
as measured from the start of first-line chemotherapy, confirm the
benefit of BAVENCIO first-line maintenance in key subgroups of patients
with advanced urothelial carcinoma that has not progressed on
platinum-based chemotherapy, including those who have low tumor burden
and in those with mixed histologic subtypes. These findings further
support the use of the JAVELIN Bladder regimen as a standard of care in
this setting and as an important first-line treatment regimen for
patients with low tumor burden in particular, where pronounced efficacy
with BAVENCIO (vs BSC alone) was observed.
Health-related
quality-of-life data for TEPMETKO® (tepotinib) in NSCLC (Abstract 8575).
This analysis reports health-related quality of life (HRQoL) outcomes
from the Phase II VISION study of TEPMETKO in patients with metastatic
non-small cell lung cancer (NSCLC) harboring METex14 skipping
alterations with brain, liver, adrenal or bone metastases. These
patients experienced stable HRQoL during treatment with TEPMETKO, with
trends for improvement in cough, consistent with results for the overall
population.
Additional company-sponsored activity at ASCO:
Medical Evening Lecture
What's new in LA SCCHN? An evasive enemy and an evolving landscape
Faculty:
Kevin Harrington (chair), Institute of Cancer Research, UK; Ari
Rosenberg, University of Chicago Medicine, USA; Jonathan Schoenfeld,
Dana-Farber Cancer Institute, USA; Sue Yom, University of California,
San Francisco, USA
June 2, 2024, 7:00PM-8:00PM CDT
W Chicago City Center hotel (172 West Adams Street), Great Room I
Select Merck-related abstracts accepted for the ASCO 2024 Annual Meeting include (all times in CDT):
Title
Lead Author
Abstract
Session Information
M9140
First-in-human
trial of M9140, an anti-CEACAM5 antibody-drug conjugate (ADC) with
exatecan payload, in patients with metastatic colorectal cancer.
Kopetz, S
3000
Session Title: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology, HALL D1
Date: Saturday June 1, 2024
Session Time: 3:00-6:00PM
Presentation Time: 3:00-3:06PM
Location: Hall D1
DDRi
A phase I study of highly potent oral ATR inhibitor tuvusertib plus oral PARP inhibitor niraparib in patients with solid tumors.
Yap, T
3018
Session Title: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology
Date: Monday June 3, 2024
Session Time: 8:00 -9:30AM
Presentation Time: 9:00-9:12AM
Location: S406
Pharmacodynamic
and immunophenotyping analyses of ATR inhibitor tuvusertib + ATM
inhibitor lartesertib in a phase Ib study in patients with advanced
unresectable solid tumors.
Boni, V
2612
Session Title: Developmental Therapeutics—Immunotherapy
Date: Saturday June 1, 2024
Session Time: 9:00AM-12:00PM
Location: Hall A
Pharmacokinetic
and pharmacodynamic findings from a phase 1b study of ATR inhibitor
tuvusertib + anti-PD-L1 avelumab in patients with advanced unresectable
solid tumors.
Tolcher, A
2614
Session Title: Developmental Therapeutics—Immunotherapy
Date: Saturday June 1, 2024
Session Time: 9:00AM-12:00PM
Location: Hall A
Xevinapant
Phase 2 study of xevinapant + chemoradiotherapy (CRT) vs placebo + CRT in patients with unresected
locally
advanced squamous cell carcinoma of the head and neck: A post hoc
activity analysis by blinded independent review committee evaluation.
Bourhis, J
e18039
Accepted for e-publication
Xevinapant
with radiation and concurrent carboplatin and paclitaxel in patients
ineligible for cisplatin with locoregionally advanced squamous cell
carcinoma of the head and neck (The EXtRaCT study)
Mir, NA
TPS6126
Session Title: Head and Neck Cancer
Date: Sunday June 2, 2024
Session Time: 9:00AM-12:00PM
Location: Hall A
BAVENCIO (avelumab)
Avelumab
first-line maintenance for advanced urothelial carcinoma: Long-term
outcomes from JAVELIN Bladder 100 in patients with low tumor burden.
Bellmunt, J
4566
Session Title: Genitourinary Cancer—Kidney and Bladder
Date: Sunday June 2, 2024
Session Time: 9:00AM-12:00PM
Location: Hall A
Avelumab
first-line maintenance for advanced urothelial carcinoma: Long-term
outcomes from the JAVELIN Bladder 100 trial in patients with
histological subtypes.
Loriot, Y
4567
Session Title: Genitourinary Cancer—Kidney and Bladder
Date: Sunday June 2, 2024
Session Time: 9:00AM-12:00PM
Location: Hall A
Avelumab
+ axitinib vs sunitinib in patients with advanced renal cell carcinoma:
Final overall survival (OS) analysis from the JAVELIN Renal 101 phase 3
trial.
Motzer, R
4508
Session Title: Genitourinary Cancer—Kidney and Bladder
Date: Monday June 3, 2024
Session Time: 8:00-11:00AM
Presentation Time: 10:12-10:24AM
Location: Hall B1
ERBITUX (cetuximab)
Efficacy of FOLFIRI plus bevacizumab versus FOLFIRI plus cetuximab in RAS-mutant metastatic
colorectal cancer: Final update on RAS mutant patients treated in FIRE-3.
Weiss, L
3550
Session Title: Gastrointestinal Cancer—Colorectal and Anal
Date: Saturday June 1, 2024
Session Time: 1:30-4:30PM
Location: Hall A
Encorafenib
and cetuximab versus irinotecan/cetuximab or FOLFIRI/cetuximab in
Chinese patients with BRAF V600E mutant metastatic colorectal cancer:
The NAUTICAL CRC study.
Wang, X
LBA3559
Session Title: Gastrointestinal Cancer—Colorectal and Anal
Date: Saturday June 1, 2024
Session Time: 1:30-4:30PM
Location: Hall A
TEPMETKO (tepotinib)
Health-related
quality of life with tepotinib in patients with MET exon 14 (METex14)
skipping non-small cell lung cancer with brain, liver, adrenal, or bone
metastases in the phase II VISION trial.
Reinmuth, N
8575
Session Title: Lung Cancer—Non-Small Cell Metastatic
Date: Monday June 3, 2024
Session Time: 1:30 -4:30PM
Location: Hall A
Advancing the Future of Cancer Care
At
Merck, we strive every day to improve the futures of people living with
cancer. Our research explores the full potential of promising
mechanisms in cancer research, focused on synergistic approaches
designed to hit cancer at its core. We are determined to maximize the
impact of our standard-of-care treatments and to continue pioneering
novel medicines. Our vision is to create a world where more cancer
patients will become cancer survivors. Learn more at
www.merckgrouponcology.com.
About M9140
M9140 is an
investigational anti-CEACAM5 antibody-drug conjugate (ADC). Leveraging
the company’s novel linker-payload technology, M9140 is the first
CEACAM5 ADC with an exatecan payload, a potent topoisomerase inhibitor
(TOP1i), which has been rationally designed for stability in circulation
and superior cancer cell killing activity. Beyond the direct effect on
the target cell, M9140 has been shown in preclinical research to induce
tumor cell death through a bystander effect permeating the cell membrane
to neighboring cells, inducing apoptosis (cell death). This bystander
effect within the tumor microenvironment may enhance efficacy,
particularly in tumors with heterogenous CEACAM5 expression. M9140 is
currently being investigated in advanced solid tumors in a
first-in-human, Phase I dose-escalation clinical trial (NCT05464030).
About Tuvusertib
Tuvusertib
(M1774), is the lead asset in the company’s portfolio of DNA damage
response inhibitors. Tuvusertib is an investigational, potentially
best-in-class small-molecule oral inhibitor of the ataxia telangiectasia
and Rad3-related (ATR) kinase, which serves as a major regulator of the
replication stress response. Early clinical data for tuvusertib have
shown potency, selectivity, and the potential to achieve high
therapeutic doses without rate-limiting side effects. The company’s
DDRiver™ Clinical Trial Program is exploring the potential of tuvusertib
as a backbone therapy in a variety of combinations with other DDR
inhibitors, immune checkpoint inhibitors, or cytotoxic agents, touching
on multiple clinical hypotheses across several types of cancer.
About Xevinapant
Xevinapant
(formerly known as Debio 1143) is an investigational first-in-class
potent oral small-molecule IAP (inhibitor of apoptosis protein)
inhibitor developed for the treatment of LA SCCHN, with a proposed dual
mechanism of action: xevinapant releases the brakes on apoptosis and
increases anti-tumor immunity, re-initiating the programmed cell death
of tumor cells. Via this dual mechanism, xevinapant is thought to
enhance the effects of chemo- and radiotherapy. Xevinapant has
demonstrated improved efficacy outcomes in combination with
chemoradiotherapy (CRT), including 18-month locoregional control,
three-year progression-free survival and five-year survival, compared
with placebo plus CRT in a Phase II study in patients with unresected LA
SCCHN. Xevinapant is being studied in two Phase III studies: TrilynX™,
in patients with unresected LA SCCHN, and XRay Vision™, in patients with
resected LA SCCHN who are at a high risk of recurrence and who are
deemed cisplatin-ineligible. In March 2021, Merck gained exclusive
rights from Debiopharm to develop and commercialize xevinapant
worldwide. Xevinapant is not approved for any use anywhere in the world.
About BAVENCIO® (avelumab)
BAVENCIO
is a human anti-programmed death ligand-1 (PD-L1) antibody. BAVENCIO
has been shown in preclinical models to engage both the adaptive and
innate immune functions. By blocking the interaction of PD-L1 with PD-1
receptors, BAVENCIO has been shown to release the suppression of the T
cell-mediated antitumor immune response in preclinical models.
BAVENCIO Approved Indications
The
European Commission (EC) has authorized the use of BAVENCIO as
monotherapy for the first-line maintenance treatment of adult patients
with locally advanced or metastatic urothelial carcinoma (UC) who are
progression-free following platinum-based chemotherapy. BAVENCIO in
combination with axitinib is indicated for the first-line treatment of
adult patients with advanced renal cell carcinoma (RCC). BAVENCIO is
also authorized by the EC for use as a monotherapy for the treatment of
adult patients with metastatic Merkel cell carcinoma (MCC).
In
the US, BAVENCIO is indicated for the maintenance treatment of patients
with locally advanced or metastatic urothelial carcinoma (UC) that has
not progressed with first-line platinum-containing chemotherapy.
BAVENCIO is also indicated for the treatment of patients with locally
advanced or metastatic UC who have disease progression during or
following platinum-containing chemotherapy, or have disease progression
within 12 months of neoadjuvant or adjuvant treatment with
platinum-containing chemotherapy.
BAVENCIO in combination with
axitinib is indicated in the US for the first-line treatment of patients
with advanced RCC. Additionally, the US Food and Drug Administration
(FDA) has approved BAVENCIO for the treatment of adults and pediatric
patients 12 years and older with metastatic MCC.
BAVENCIO is currently approved for at least one indication for patients in more than 50 countries.
BAVENCIO Safety Profile from the EU Summary of Product Characteristics (SmPC)
The
special warnings and precautions for use for BAVENCIO monotherapy
include infusion-related reactions, as well as immune-related adverse
reactions that include pneumonitis and hepatitis (including fatal
cases), colitis, pancreatitis (including fatal cases), myocarditis
(including fatal cases), endocrinopathies, nephritis and renal
dysfunction, and other immune-related adverse reactions. The special
warnings and precautions for use for BAVENCIO in combination with
axitinib include hepatotoxicity.
The SmPC list of the most common
adverse reactions with BAVENCIO monotherapy in patients with solid
tumors includes fatigue, nausea, diarrhea, decreased appetite,
constipation, infusion-related reactions, weight decreased and vomiting.
The list of most common adverse reactions with BAVENCIO in combination
with axitinib includes diarrhea, hypertension, fatigue, nausea,
dysphonia, decreased appetite, hypothyroidism, cough, headache, dyspnea,
and arthralgia.
About TEPMETKO® (tepotinib)
TEPMETKO is a
once-daily oral MET inhibitor that inhibits the oncogenic MET receptor
signaling caused by MET (gene) alterations. Discovered and developed
in-house at Merck, TEPMETKO has a highly selective mechanism of action,
with the potential to improve outcomes in aggressive tumors that have a
poor prognosis and harbor these specific alterations.
TEPMETKO is
the first oral MET inhibitor to have received a regulatory approval
anywhere in the world for the treatment of advanced non-small cell lung
cancer (NSCLC) harboring MET exon 14 skipping alterations, with its
approval in Japan in March 2020. In February 2024, the US Food and Drug
Administration granted full approval for TEPMETKO. The conversion from
accelerated approval, which the company received in February 2021, to
full FDA approval is based on additional data from the ongoing Phase II
VISION study, the largest trial of its kind. The updated label includes
revised data for overall response rate and duration of response, as well
as safety outcomes for more than 300 patients who were treated with
TEPMETKO once-daily for metastatic NSCLC with METex14 skipping
alterations.
TEPMETKO is available in a number of countries. To
meet an urgent clinical need, TEPMETKO is also available in a pilot zone
of China in line with the government policy to drive early access for
innovative medicines approved outside of China.
TEPMETKO Safety Profile from the EU Summary of Product Characteristics (SmPC)
The
special warnings and precautions for use for TEPMETKO monotherapy
include Interstitial lung disease (ILD) or ILD-like adverse reactions
including pneumonitis, increase of liver enzymes (ALT and AST), QTc
prolongation, and embryo-fetal toxicity.
The most common adverse
reactions in ≥ 20% of exposed to tepotinib at the recommended dose in
the target indication are oedema, mainly peripheral oedema, nausea,
hypoalbuminemia, diarrhea and increase in creatinine. The most common
serious adverse reactions in ≥ 1% of patients are peripheral oedema,
generalized oedema and ILD.
About ERBITUX® (cetuximab)
ERBITUX
is an IgG1 monoclonal antibody targeting the epidermal growth factor
receptor (EGFR). As a monoclonal antibody, the mode of action of ERBITUX
is distinct from standard non-selective chemotherapy treatments in that
it specifically targets and binds to the EGFR. This binding inhibits
the activation of the receptor and the subsequent signal-transduction
pathway, which results in reducing both the invasion of normal tissues
by tumor cells and the spread of tumors to new sites. It is also
believed to inhibit the ability of tumor cells to repair the damage
caused by chemotherapy and radiotherapy and to inhibit the formation of
new blood vessels inside tumors, which appears to lead to an overall
suppression of tumor growth. Based on in vitro evidence, ERBITUX also
targets cytotoxic immune effector cells towards EGFR-expressing tumor
cells (antibody-dependent cell-mediated cytotoxicity [ADCC]).
ERBITUX
has already obtained market authorization in over 100 countries
worldwide for the treatment of RAS wild-type metastatic colorectal
cancer and for the treatment of squamous cell carcinoma of the head and
neck. Merck licensed the right to market ERBITUX, a registered trademark
of ImClone LLC, outside the U.S. and Canada from ImClone LLC, a wholly
owned subsidiary of Eli Lilly and Company, in 1998.
About Merck
Merck,
a leading science and technology company, operates across life science,
healthcare and electronics. Around 63,000 employees work to make a
positive difference to millions of people’s lives every day by creating
more joyful and sustainable ways to live. From providing products and
services that accelerate drug development and manufacturing as well as
discovering unique ways to treat the most challenging diseases to
enabling the intelligence of devices – the company is everywhere. In
2023, Merck generated sales of € 21 billion in 65 countries.
Scientific
exploration and responsible entrepreneurship have been key to Merck’s
technological and scientific advances. This is how Merck has thrived
since its founding in 1668. The founding family remains the majority
owner of the publicly listed company. Merck holds the global rights to
the Merck name and brand. The only exceptions are the United States and
Canada, where the business sectors of Merck operate as MilliporeSigma in
life science, EMD Serono in healthcare, and EMD Electronics in
electronics.
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