- 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
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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