- 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 UK-based
media
EMD Serono, the Healthcare business of Merck KGaA, Darmstadt,
Germany, in the U.S. and Canada, 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 KGaA, Darmstadt,
Germany. “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 KGaA, Darmstadt, Germany-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
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 EMD Serono, 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.emdseronooncology.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 KGaA, Darmstadt, Germany, 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
BAVENCIO® (avelumab) is indicated in the US 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 renal cell
carcinoma (RCC).
In the US, BAVENCIO is indicated for the treatment of adults and
pediatric patients 12 years and older with metastatic Merkel cell
carcinoma (MCC).
BAVENCIO is currently approved for at least one indication for
patients in more than 50 countries.
BAVENCIO Important Safety Information from the US
FDA-Approved Label
BAVENCIO can cause severe and fatal immune-mediated adverse
reactions in any organ system or tissue and at any time after
starting treatment with a PD-1/PD-L1 blocking antibody, including
after discontinuation of treatment.
Early identification and management of immune-mediated
adverse reactions are essential to ensure safe use of
PD-1/PD-L1 blocking antibodies. Monitor patients closely for
symptoms and signs that may be clinical manifestations of
underlying immune-mediated adverse reactions. Evaluate liver
enzymes, creatinine, and thyroid function at baseline and
periodically during treatment. In cases of suspected
immune-mediated adverse reactions, initiate appropriate workup to
exclude alternative etiologies, including infection. Institute
medical management promptly, including specialty consultation as
appropriate.
No dose reduction for BAVENCIO is recommended. For
immune-mediated adverse reactions, withhold or permanently
discontinue BAVENCIO depending on severity. In general,
withhold BAVENCIO for severe (Grade 3) immune-mediated adverse
reactions. Permanently discontinue BAVENCIO for life-threatening
(Grade 4) immune-mediated adverse reactions, recurrent severe
(Grade 3) immune-mediated reactions that require systemic
immunosuppressive treatment, or an inability to reduce
corticosteroid dose to 10 mg or less of prednisone or equivalent
per day within 12 weeks of initiating corticosteroids. In general,
if BAVENCIO requires interruption or discontinuation, administer
systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or
equivalent) until improvement to Grade 1 or less. Upon improvement
to Grade 1 or less, initiate corticosteroid taper and continue to
taper over at least 1 month. Consider administration of other
systemic immunosuppressants in patients whose immune-mediated
adverse reactions are not controlled with corticosteroid therapy.
Toxicity management guidelines for adverse reactions that do not
necessarily require systemic corticosteroids (eg, endocrinopathies
and dermatologic reactions) are discussed in subsequent
sections.
BAVENCIO can cause immune-mediated pneumonitis, including
fatal cases. Monitor patients for signs and symptoms of pneumonitis
and evaluate suspected cases with radiographic imaging. Administer
corticosteroids for Grade 2 or greater pneumonitis. Withhold
BAVENCIO for Grade 2 and permanently discontinue for Grade 3 or
Grade 4 pneumonitis. Immune-mediated pneumonitis occurred in 1.2%
(21/1738) of patients, including fatal (0.1%), Grade 4 (0.1%),
Grade 3 (0.3%) and Grade 2 (0.6%) adverse reactions. Systemic
corticosteroids were required in all (21/21) patients with
pneumonitis.
BAVENCIO can cause immune-mediated colitis. The primary
component of immune-mediated colitis consisted of diarrhea.
Cytomegalovirus infection/reactivation has been reported in
patients with corticosteroid-refractory immune-mediated colitis. In
cases of corticosteroid-refractory colitis, consider repeating
infectious workup to exclude alternative etiologies. Withhold
BAVENCIO for Grade 2 or Grade 3, and permanently discontinue for
Grade 4 colitis. Immune-mediated colitis occurred in 1.5% (26/1738)
of patients, including Grade 3 (0.4%) and Grade 2 (0.7%) adverse
reactions. Systemic corticosteroids were required in all (26/26)
patients with colitis.
BAVENCIO can cause hepatotoxicity and immune-mediated
hepatitis. Withhold or permanently discontinue BAVENCIO based
on tumor involvement of the liver and severity of aspartate
aminotransferase (AST), alanine aminotransferase (ALT), or total
bilirubin elevation. Immune-mediated hepatitis occurred with
BAVENCIO as a single agent in 0.9% (16/1738) of patients, including
fatal (0.1%), Grade 3 (0.6%), and Grade 2 (0.1%) adverse reactions.
Systemic corticosteroids were required in all (16/16) patients with
hepatitis.
BAVENCIO in combination with axitinib can cause
hepatotoxicity with higher than expected frequencies of
Grade 3 and 4 ALT and AST elevation compared to BAVENCIO alone.
Consider more frequent monitoring of liver enzymes as compared to
when the drugs are used as monotherapy. Withhold or permanently
discontinue both BAVENCIO and axitinib based on severity of AST,
ALT, or total bilirubin elevation, and consider administering
corticosteroids as needed. Consider rechallenge with BAVENCIO or
axitinib, or sequential rechallenge with both BAVENCIO and
axitinib, after recovery. In patients treated with BAVENCIO in
combination with axitinib in the advanced RCC trials, increased ALT
and increased AST were reported in 9% (Grade 3) and 7% (Grade 4) of
patients. Immune-mediated hepatitis was reported in 7% of patients
including 4.9% with Grade 3 or 4 immune-mediated hepatitis.
Thirty-four patients were treated with corticosteroids and one
patient was treated with a non-steroidal immunosuppressant.
BAVENCIO can cause primary or secondary immune-mediated
adrenal insufficiency. For Grade 2 or higher adrenal
insufficiency, initiate symptomatic treatment, including hormone
replacement, as clinically indicated. Withhold BAVENCIO for Grade 3
or Grade 4 endocrinopathies until clinically stable or permanently
discontinue depending on severity. Immune-mediated adrenal
insufficiency occurred in 0.5% (8/1738) of patients, including
Grade 3 (0.1%) and Grade 2 (0.3%) adverse reactions. Systemic
corticosteroids were required in all (8/8) patients with adrenal
insufficiency.
BAVENCIO can cause immune-mediated hypophysitis.
Hypophysitis can present with acute symptoms associated with mass
effect such as headache, photophobia, or visual field defects.
Hypophysitis can cause hypopituitarism. Initiate hormone
replacement, as clinically indicated. Withhold BAVENCIO for Grade 3
or Grade 4 endocrinopathies until clinically stable or permanently
discontinue depending on severity. Immune-mediated pituitary
disorders occurred in 0.1% (1/1738) of patients, which was a Grade
2 (0.1%) adverse reaction.
BAVENCIO can cause immune-mediated thyroid disorders.
Thyroiditis can present with or without endocrinopathy.
Hypothyroidism can follow hyperthyroidism. Initiate hormone
replacement for hypothyroidism or institute medical management of
hyperthyroidism, as clinically indicated. Withhold BAVENCIO for
Grade 3 or Grade 4 endocrinopathies until clinically stable or
permanently discontinue depending on severity. Thyroiditis occurred
in 0.2% (4/1738) of patients, including Grade 2 (0.1%) adverse
reactions. Hyperthyroidism occurred in 0.4% (7/1738) of patients,
including Grade 2 (0.3%) adverse reactions. Systemic
corticosteroids were required in 29% (2/7) of patients with
hyperthyroidism. Hypothyroidism occurred in 5% (90/1738) of
patients, including Grade 3 (0.2%) and Grade 2 (3.7%) adverse
reactions. Systemic corticosteroids were required in 7% (6/90) of
patients with hypothyroidism.
BAVENCIO can cause immune-mediated type I diabetes
mellitus, which can present with diabetic ketoacidosis. Monitor
patients for hyperglycemia or other signs and symptoms of diabetes.
Initiate treatment with insulin as clinically indicated. Withhold
BAVENCIO for Grade 3 or Grade 4 endocrinopathies until clinically
stable or permanently discontinue depending on severity.
Immune-mediated type I diabetes mellitus occurred in 0.1% (2/1738)
of patients, including Grade 3 (0.1%) adverse reactions.
BAVENCIO can cause immune-mediated nephritis with renal
dysfunction. Withhold BAVENCIO for Grade 2 or Grade 3, and
permanently discontinue for Grade 4 increased blood creatinine.
Immune-mediated nephritis with renal dysfunction occurred in 0.1%
(1/1738) of patients, which was a Grade 2 (0.1%) adverse reaction.
Systemic corticosteroids were required in this patient.
BAVENCIO can cause immune-mediated dermatologic adverse
reactions, including rash or dermatitis. Exfoliative dermatitis
including Stevens Johnson Syndrome (SJS), drug rash with
eosinophilia and systemic symptoms (DRESS), and toxic epidermal
necrolysis (TEN), has occurred with PD-1/PD-L1 blocking antibodies.
Topical emollients and/or topical corticosteroids may be adequate
to treat mild to moderate non-exfoliative rashes. Withhold BAVENCIO
for suspected and permanently discontinue for confirmed SJS, TEN,
or DRESS. Immune-mediated dermatologic adverse reactions occurred
in 5% (90/1738) of patients, including Grade 3 (0.1%) and Grade 2
(2.0%) adverse reactions. Systemic corticosteroids were required in
29% (26/90) of patients with dermatologic adverse reactions.
BAVENCIO can result in other immune-mediated adverse
reactions. Other clinically significant immune-mediated adverse
reactions occurred at an incidence of <1% in patients who
received BAVENCIO or were reported with the use of other PD-1/PD-L1
blocking antibodies. For myocarditis, permanently discontinue
BAVENCIO for Grade 2, Grade 3, or Grade 4. For neurological
toxicities, withhold BAVENCIO for Grade 2 and permanently
discontinue for Grade 3 or Grade 4.
BAVENCIO can cause severe or life-threatening
infusion-related reactions. Premedicate patients with an
antihistamine and acetaminophen prior to the first 4 infusions and
for subsequent infusions based upon clinical judgment and
presence/severity of prior infusion reactions. Monitor patients for
signs and symptoms of infusion-related reactions, including
pyrexia, chills, flushing, hypotension, dyspnea, wheezing, back
pain, abdominal pain, and urticaria. Interrupt or slow the rate of
infusion for Grade 1 or Grade 2 infusion-related reactions.
Permanently discontinue BAVENCIO for Grade 3 or Grade 4
infusion-related reactions. Infusion-related reactions occurred in
25% of patients, including three (0.2%) Grade 4 and nine (0.5%)
Grade 3 infusion-related reactions. Eleven (92%) of the 12 patients
with Grade ≥3 reactions were treated with intravenous
corticosteroids.
Fatal and other serious complications of allogeneic
hematopoietic stem cell transplantation (HSCT) can occur in
patients who receive HSCT before or after being treated with a
PD-1/PD-L1 blocking antibody. Follow patients closely for evidence
of transplant-related complications and intervene promptly.
Consider the benefit versus risks of treatment with a PD-1/PD-L1
blocking antibody prior to or after an allogeneic HSCT.
BAVENCIO in combination with axitinib can cause major
adverse cardiovascular events (MACE) including severe and fatal
events. Consider baseline and periodic evaluations of left
ventricular ejection fraction. Monitor for signs and symptoms of
cardiovascular events. Optimize management of cardiovascular risk
factors, such as hypertension, diabetes, or dyslipidemia.
Permanently discontinue BAVENCIO and axitinib for Grade 3-4
cardiovascular events. MACE occurred in 7% of patients with
advanced RCC treated with BAVENCIO in combination with axitinib
compared to 3.4% treated with sunitinib in a randomized trial.
These events included death due to cardiac events (1.4%), Grade 3-4
myocardial infarction (2.8%), and Grade 3-4 congestive heart
failure (1.8%).
BAVENCIO can cause fetal harm when administered to a
pregnant woman. Advise patients of the potential risk to a fetus
including the risk of fetal death. Advise females of childbearing
potential to use effective contraception during treatment with
BAVENCIO and for at least 1 month after the last dose of BAVENCIO.
It is not known whether BAVENCIO is excreted in human milk. Advise
a lactating woman not to breastfeed during treatment and for
at least 1 month after the last dose of BAVENCIO due to the
potential for serious adverse reactions in breastfed infants.
The most common adverse reactions (all grades, ≥20%) in
patients with metastatic Merkel cell carcinoma (MCC) were
fatigue (50%), musculoskeletal pain (32%), diarrhea (23%), nausea
(22%), infusion-related reaction (22%), rash (22%), decreased
appetite (20%), and peripheral edema (20%).
Selected treatment-emergent laboratory abnormalities (all
grades, ≥20%) in patients with metastatic MCC were
lymphopenia (49%), anemia (35%), increased aspartate
aminotransferase (34%), thrombocytopenia (27%), and increased
alanine aminotransferase (20%).
A fatal adverse reaction (sepsis) occurred in one (0.3%)
patient with locally advanced or metastatic urothelial carcinoma
(UC) receiving BAVENCIO + best supportive care (BSC) as
first-line maintenance treatment. In patients with previously
treated locally advanced or metastatic UC, fourteen patients (6%)
who were treated with BAVENCIO experienced either pneumonitis,
respiratory failure, sepsis/urosepsis, cerebrovascular accident, or
gastrointestinal adverse events, which led to death.
The most common adverse reactions (all grades, ≥20%) in
patients with locally advanced or metastatic UC receiving
BAVENCIO + BSC (vs BSC alone) as first-line maintenance treatment
were fatigue (35% vs 13%), musculoskeletal pain (24% vs 15%),
urinary tract infection (20% vs 11%), and rash (20% vs 2.3%). In
patients with previously treated locally advanced or metastatic UC
receiving BAVENCIO, the most common adverse reactions (all grades,
≥20%) were fatigue, infusion-related reaction, musculoskeletal
pain, nausea, decreased appetite, and urinary tract infection.
Selected laboratory abnormalities (all grades, ≥20%) in
patients with locally advanced or metastatic UC receiving
BAVENCIO + BSC (vs BSC alone) as first-line maintenance treatment
were blood triglycerides increased (34% vs 28%), alkaline
phosphatase increased (30% vs 20%), blood sodium decreased (28% vs
20%), lipase increased (25% vs 16%), aspartate aminotransferase
(AST) increased (24% vs 12%), blood potassium increased (24% vs
16%), alanine aminotransferase (ALT) increased (24% vs 12%), blood
cholesterol increased (22% vs 16%), serum amylase increased (21% vs
12%), hemoglobin decreased (28% vs 18%), and white blood cell
decreased (20% vs 10%).
Fatal adverse reactions occurred in 1.8% of patients with
advanced renal cell carcinoma (RCC) receiving BAVENCIO in
combination with axitinib. These included sudden cardiac death
(1.2%), stroke (0.2%), myocarditis (0.2%), and necrotizing
pancreatitis (0.2%).
The most common adverse reactions (all grades, ≥20%) in
patients with advanced RCC receiving BAVENCIO in combination
with axitinib (vs sunitinib) were diarrhea (62% vs 48%), fatigue
(53% vs 54%), hypertension (50% vs 36%), musculoskeletal pain (40%
vs 33%), nausea (34% vs 39%), mucositis (34% vs 35%),
palmar-plantar erythrodysesthesia (33% vs 34%), dysphonia (31% vs
3.2%), decreased appetite (26% vs 29%), hypothyroidism (25% vs
14%), rash (25% vs 16%), hepatotoxicity (24% vs 18%), cough (23% vs
19%), dyspnea (23% vs 16%), abdominal pain (22% vs 19%), and
headache (21% vs 16%).
Selected laboratory abnormalities (all grades, ≥20%)
worsening from baseline in patients with advanced RCC
receiving BAVENCIO in combination with axitinib (vs sunitinib) were
blood triglycerides increased (71% vs 48%), blood creatinine
increased (62% vs 68%), blood cholesterol increased (57% vs 22%),
alanine aminotransferase increased (ALT) (50% vs 46%), aspartate
aminotransferase increased (AST) (47% vs 57%), blood sodium
decreased (38% vs 37%), lipase increased (37% vs 25%), blood
potassium increased (35% vs 28%), platelet count decreased (27% vs
80%), blood bilirubin increased (21% vs 23%), and hemoglobin
decreased (21% vs 65%).
Please see full US Prescribing Information and Medication Guide
available at http://www.BAVENCIO.com.
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 KGaA, Darmstadt,
Germany, 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 gene
alterations, with its approval in Japan in March 2020. In February
2022, the European Commission (EC) approved once-daily oral
TEPMETKO as monotherapy for the treatment of adult patients with
advanced NSCLC harboring alterations leading to
mesenchymal-epithelial transition factor gene exon 14 (METex14)
skipping, who require systemic therapy following prior treatment
with immunotherapy and/or platinum-based chemotherapy. 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 has been granted market authorization in a number of
countries/regions and is marketed in 30+ countries (including
‘named patient use’ programs). Submissions and reviews of
applications to medical authorities in other regions are
ongoing.
TEPMETKO Approved Indications
TEPMETKO is indicated in the US for the treatment of adult
patients with metastatic non-small cell lung cancer (NSCLC)
harboring mesenchymal-epithelial transition (MET) exon 14 skipping
alterations.
TEPMETKO Important Safety Information From the FDA-Approved
Label
TEPMETKO can cause interstitial lung disease
(ILD)/pneumonitis, which can be fatal. Monitor patients for new
or worsening pulmonary symptoms indicative of ILD/pneumonitis (eg,
dyspnea, cough, fever). Immediately withhold TEPMETKO in patients
with suspected ILD/pneumonitis and permanently discontinue if no
other potential causes of ILD/pneumonitis are identified.
ILD/pneumonitis occurred in 2% of patients treated with TEPMETKO,
with one patient experiencing a Grade 3 or higher event; this event
resulted in death.
TEPMETKO can cause hepatotoxicity, which can be fatal.
Monitor liver function tests (including alanine aminotransferase
[ALT], aspartate aminotransferase [AST], and total bilirubin) prior
to the start of TEPMETKO, every 2 weeks during the first 3 months
of treatment, then once a month or as clinically indicated, with
more frequent testing in patients who develop increased
transaminases or total bilirubin. Based on the severity of the
adverse reaction, withhold, dose reduce, or permanently discontinue
TEPMETKO. Increased ALT/increased AST occurred in 18% of patients
treated with TEPMETKO. Grade 3 or 4 increased ALT/AST occurred in
4.7% of patients. A fatal adverse reaction of hepatic failure
occurred in one patient (0.2%). The median time-to-onset of Grade 3
or higher increased ALT/AST was 47 days (range 1 to 262).
TEPMETKO can cause pancreatic toxicity in the form of
elevations in amylase and lipase levels. Increased amylase and/or
lipase occurred in 13% of patients, with Grade 3 and 4 increases
occurring in 5% and 1.2% of patients, respectively. Monitor amylase
and lipase levels at baseline and regularly during treatment with
TEPMETKO and temporarily withhold, dose reduce, or permanently
discontinue based on severity of the adverse event.
TEPMETKO can cause embryo-fetal toxicity. Based on
findings in animal studies and its mechanism of action, TEPMETKO
can cause fetal harm when administered to a pregnant woman. Advise
pregnant women of the potential risk to a fetus. Advise females of
reproductive potential or males with female partners of
reproductive potential to use effective contraception during
treatment with TEPMETKO and for one week after the last dose.
Avoid concomitant use of TEPMETKO with certain P-gp
substrates where minimal concentration changes may lead to
serious or life-threatening toxicities. If concomitant use is
unavoidable, reduce the P-gp substrate dosage if recommended in its
approved product labeling.
Fatal adverse reactions occurred in one patient (0.3%)
due to pneumonitis, one patient (0.3%) due to hepatic failure, one
patient (0.3%) due to dyspnea from fluid overload, one patient
(0.3%) due to pneumonia, one patient (0.3%) due to sepsis, and one
patient (0.3%) from unknown cause.
Serious adverse reactions occurred in 51% of patients who
received TEPMETKO. Serious adverse reactions in >2% of patients
included pleural effusion (6%), pneumonia (6%), edema (5%), general
health deterioration (3.8%), dyspnea (3.5%), musculoskeletal pain
(2.9%), and pulmonary embolism (2.2%).
The most common adverse reactions (≥20%) in patients who
received TEPMETKO were edema (81%), nausea (31%), fatigue (30%),
musculoskeletal pain (30%), diarrhea (29%), dyspnea (24%), rash
(21%), and decreased appetite (21%).
Clinically relevant adverse reactions in <10% of
patients who received TEPMETKO included ILD/pneumonitis, fever,
dizziness, pruritus, and headache.
Selected laboratory abnormalities (≥20%) from baseline in
patients receiving TEPMETKO in descending order were: decreased
albumin (81%), increased creatinine (60%), decreased lymphocytes
(57%), increased alkaline phosphatase (ALP) (52%), increased ALT
(50%), increased AST (40%), decreased sodium (36%), decreased
hemoglobin (31%), increased gamma-glutamyltransferase (GGT) (29%),
increased potassium (26%), increased amylase (25%), decreased
leukocytes (25%), decreased platelets (24%), and increased lipase
(21%).
The most common Grade 3-4 laboratory abnormalities (≥2%)
in descending order were: decreased lymphocytes (15%), decreased
albumin (9%), decreased sodium (9%), increased GGT (6%), increased
amylase (5%), increased lipase (5%), increased ALT (4.9%),
increased AST (3.6%), and decreased hemoglobin (3.6%).
Please see the full US Prescribing Information
for TEPMETKO.
About EMD Serono, Inc.
EMD Serono - the healthcare business of Merck KGaA, Darmstadt,
Germany in the U.S. and Canada -aspires to create, improve and
prolong life for people living with difficult-to-treat conditions
like infertility, multiple sclerosis and cancer. The business is
imagining the future of healthcare by working to translate the
discovery of molecules into potentially meaningful outcomes for
people with serious unmet medical needs. EMD Serono’s global roots
go back more than 350 years with Merck KGaA, Darmstadt, Germany.
Today, the business has approximately 1,500 employees around the
country with commercial, clinical and research operations in
Massachusetts. www.emdserono.com.
About Merck KGaA, Darmstadt, Germany
Merck KGaA, Darmstadt, Germany, a leading science and technology
company, operates across life science, healthcare and electronics.
More than 64,000 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 2022, Merck KGaA, Darmstadt, Germany, generated sales of € 22.2
billion in 66 countries.
The company holds the global rights to the name and trademark
“Merck” internationally. The only exceptions are the United States
and Canada, where the business sectors of Merck KGaA, Darmstadt,
Germany, operate as MilliporeSigma in life science, EMD Serono in
healthcare and EMD Electronics in electronics. Since its founding
in 1668, scientific exploration and responsible entrepreneurship
have been key to the company’s technological and scientific
advances. To this day, the founding family remains the majority
owner of the publicly listed company.
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version on businesswire.com: https://www.businesswire.com/news/home/20240523083710/en/
Media Relations noelle.piscitelli@emdserono.com Phone: +1
(781) 427-4351