- CANOVA study
evaluated venetoclax plus dexamethasone in patients with
t(11;14)-positive multiple myeloma compared to pomalidomide plus
dexamethasone
- Results are being presented at the International
Myeloma Society Annual Meeting in Athens,
Greece
- AbbVie will discuss the data with health authorities
in the near future to further understand the potential of
venetoclax as a biomarker-driven therapy in multiple
myeloma
NORTH
CHICAGO, Ill., Sept. 29,
2023 /PRNewswire/ -- AbbVie (NYSE: ABBV) today
announced data from its Phase 3 CANOVA study evaluating the safety
and efficacy of venetoclax (VENCLEXTA®/
VENCLYXTO®) plus dexamethasone (VenDex) for patients
with t(11;14)-positive relapsed or refractory (R/R) multiple
myeloma who have received two or more prior treatments. Data did
not demonstrate that the treatment combination significantly
improved progression-free survival (PFS), the primary endpoint of
the trial. Patients receiving VenDex showed improvement in median
PFS of 9.9 months compared to 5.8 months with the
combination of study comparator pomalidomide and dexamethasone
(PomDex); however, the results did not reach statistical
significance [HR = 0.823, 95% CI: (0.596, 1.136);
p-value of 0.237].
Select prespecified secondary endpoints from the
CANOVA trial include the
following:
- Overall response rate (ORR): 62% in VenDex vs. 35% in
PomDex (nominal p-value of <0.001)
- Rate of very good partial response or better (VGPR) at
39% in VenDex vs. 14% in PomDex (nominal p-value of
<0.001)
- Median overall survival (OS) was 32.4 months in VenDex
vs. 24.5 months in PomDex [HR of 0.697 (95% CI: 0.472, 1.029);
nominal p-value of 0.067]
Additional prespecified analyses include:
- PFS per investigator which resulted in a median PFS of
9.1 months with VenDex vs 4.9 months with PomDex [HR = 0.737, (95%
CI: 0.543, 1.000); nominal p-value of 0.050]
- Median time to next treatment (TTNT) which was longer in
the VenDex arm 21.2 months vs. 8.3 months in the PomDex arm [HR of
0.546 (95% CI: 0.385, 0.776); nominal p-value of 0.001]
The safety profile of the combination of venetoclax and
dexamethasone in the trial was generally consistent with the known
safety profiles when used as single agents and no new safety
signals have emerged. The most common adverse events (AEs)
experienced by patients (>20%) treated with VenDex included any
infection (61%), diarrhea (41%), lymphopenia (24%) and nausea
(22%). The most common AEs experienced by subjects treated with
PomDex included neutropenia (63%), any infection (57%),
thrombocytopenia (39%) and anemia (35%).
Multiple myeloma is the second most common blood cancer in
the world.1 Many patients experience poor outcomes as
most eventually relapse despite recent treatment advances. A subset
of patients have the t(11;14) biomarker, the most common
chromosomal translocation in multiple myeloma, that can signal an
overexpression of the BCL-2 protein.2
"While the CANOVA trial
did not meet its primary endpoint, given the potential favorable
trends seen in the study, we will discuss these data with health
authorities in the near future," said Mariana Cota Stirner, M.D., Ph.D., therapeutic
area head oncology hematology, AbbVie. "We remain committed to
elevating the standard of care for blood cancer patients around the
world including patients with multiple myeloma."
Venetoclax is currently approved for patients with
previously untreated and treated chronic lymphocytic leukemia (CLL)
and newly diagnosed acute myeloid leukemia (AML). Venetoclax is not
approved by any regulatory authority in any country for the
treatment of multiple myeloma. It is jointly commercialized by
AbbVie and Genentech, a member of the Roche Group, in the U.S. and
by AbbVie outside of the U.S.
About the CANOVA
Study3
CANOVA is a Phase 3, multicenter, randomized,
open label study of either venetoclax or pomalidomide in
combination with dexamethasone in patients with t(11;14)-positive
R/R multiple myeloma. The study was initiated in 2018 and
enrolled 263 patients 18 years and older with a documented
diagnosis of multiple myeloma with t(11;14)-positive disease based
on standard International Myeloma Working Group (IMWG) criteria,
who had received at least two prior lines of therapy.
The primary endpoint of the trial was IRC-assessed PFS.
Secondary endpoints include ORR, VGPR or better response rate, OS
and MRD negativity rate defined at 10-5 threshold, as
measured by centralized testing of bone marrow aspirate samples by
next generation sequencing.
About Multiple Myeloma
Multiple
myeloma is a type of blood cancer that affects plasma cells, which
grow out of control and accumulate in the body's bone
marrow.1,4 Multiple myeloma is the second most common
blood cancer in the world.1 An estimated 176,000 people
globally were diagnosed with multiple myeloma in 2020, and 117,000
people died from the disease.5 In approximately 16% to
24% of people with multiple myeloma, t(11;14) is the most
frequently seen chromosomal translocation.2
Nearly all multiple myeloma patients eventually relapse,
which is associated with poor outcomes, and each remission is
typically shorter than the previous one.6
About
VENCLEXTA®/VENCLYXTO® (venetoclax)
VENCLEXTA/VENCLYXTO (venetoclax) is a first-in-class medicine
that selectively binds and inhibits the B-cell lymphoma-2 (BCL-2)
protein. In some blood cancers, BCL-2 prevents cancer cells from
undergoing their natural death or self-destruction process, called
apoptosis. VENCLYXTO targets the BCL-2 protein and works to help
restore the process of apoptosis.
VENCLEXTA/VENCLYXTO is being developed by AbbVie and
Roche. It is jointly commercialized by AbbVie and Genentech, a
member of the Roche Group, in the U.S. and by AbbVie outside of the
U.S. Together, the companies are committed to BCL-2 research and to
studying venetoclax in clinical trials across several blood and
other cancers. Venetoclax is approved in more than 80 countries,
including the U.S.
Indication and Important VENCLYXTO®
▼ (venetoclax) EU Safety
Information7
Indications
Venclyxto in combination with obinutuzumab is indicated
for the treatment of adult patients with previously untreated
chronic lymphocytic leukaemia (CLL).
Venclyxto in combination with rituximab is indicated for
the treatment of adult patients with CLL who have received at least
one prior therapy.
Venclyxto monotherapy is indicated for the treatment of
CLL:
- In the presence of 17p deletion
or TP53 mutation in adult patients who are
unsuitable for or have failed a B-cell receptor pathway inhibitor,
or
- In the absence of 17p deletion
or TP53 mutation in adult patients who have failed
both chemoimmunotherapy and a B-cell receptor pathway
inhibitor.
Venclyxto in combination with a hypomethylating agent is
indicated for the treatment of adult patients with newly diagnosed
acute myeloid leukaemia (AML) who are ineligible for intensive
chemotherapy.
Contraindications
Hypersensitivity to the active substance or to any of the
excipients is contraindicated. Concomitant use of strong CYP3A
inhibitors at initiation and during the dose-titration phase due to
increased risk for tumour lysis syndrome (TLS). Concomitant use of
preparations containing St. John's wort as Venclyxto
efficacy may be reduced.
Special Warnings & Precautions for
Use
Tumour Lysis syndrome, including fatal events, has
occurred in patients when treated with Venclyxto. For CLL and AML,
please refer to the indication-specific recommendations for
prevention of TLS in the Venclyxto summary of product
characteristic (SmPC).
Patients should be assessed for risk and should receive
appropriate prophylaxis, monitoring, and management for
TLS. The risk of TLS is a continuum based on multiple factors,
including comorbidities. Venclyxto poses a risk for TLS at
initiation and during the dose-titration phase. Changes in
electrolytes consistent with TLS that require prompt management can
occur as early as 6 to 8 hours following the first dose of
Venclyxto and at each dose increase.
Neutropenia (grade 3 or 4) has been
reported. Complete blood counts should be monitored throughout
the treatment period.
In patients with AML, neutropenia (grade 3 or 4) is common
before starting treatment. The neutrophil counts can worsen with
Venetoclax in combination with a hypomethylating agent. Neutropenia
can recur with subsequent cycles of therapy. Dose modification and
interruptions for cytopenias are dependent on remission
status.
For CLL and AML, please refer to the indication-specific
recommendations for dose modifications for toxicities in the
Venclyxto SmPC.
Serious infections including sepsis with fatal outcome
have been reported. Monitoring of any signs and symptoms of
infection is required. Suspected infections should receive
prompt treatment including antimicrobials and dose interruption or
reduction as appropriate.
Live vaccines should not be administered during treatment
or thereafter until B-cell recovery.
Drug Interactions
In CLL and AML CYP3A inhibitors may increase Venclyxto
plasma concentrations.
In CLL, at initiation and dose-titration phase, Strong
CYP3A inhibitors are contraindicated due to increased risk for TLS
and moderate CYP3A inhibitors should be avoided. If moderate CYP3A
inhibitors must be used, please refer to the recommendations for
dose modifications in the Venclyxto SmPC.
In AML, please refer to the AML-specific recommendation
for dose modifications for potential interactions with CYP3A
inhibitors, in the VENCLYXTO SmPC.
Avoid concomitant use of P-gp and BCRP inhibitors at
initiation and during the dose titration phase.
CYP3A4 inducers may decrease Venclyxto plasma
concentrations. Avoid coadministration with strong or
moderate CYP3A inducers. These agents may decrease venetoclax
plasma concentrations.
Co-administration of bile acid sequestrants with VENCLYXTO
is not recommended as this may reduce the absorption of
VENCLYXTO.
Adverse Reactions
CLL
The most commonly occurring adverse reactions (>=20%)
of any grade in patients receiving venetoclax in the combination
studies with obinutuzumab or rituximab were neutropenia, diarrhoea,
and upper respiratory tract infection. In the monotherapy
studies, the most common adverse reactions were
neutropenia/neutrophil count decreased, diarrhoea, nausea, anaemia,
fatigue, and upper respiratory tract infection.
The most frequently occurring serious adverse reactions
(>=2%) in patients receiving venetoclax in combination with
obinutuzumab or rituximab were pneumonia, sepsis, febrile
neutropenia, and TLS. In the monotherapy studies, the most
frequently reported serious adverse reactions (>=2%) were
pneumonia and febrile neutropenia.
Discontinuations due to adverse reactions occurred in 16%
of patients treated with venetoclax in combination with
obinutuzumab or rituximab in the CLL14 and Murano studies,
respectively. In the monotherapy studies with venetoclax, 11%
of patients discontinued due to adverse reactions.
Dosage reductions due to adverse reactions occurred in 21%
of patients treated with the combination of venetoclax and
obinutuzumab in CLL14, in 15% of patients treated with the
combination of venetoclax and rituximab in Murano, and in 14% of
patients treated with venetoclax in the monotherapy studies. The
most common adverse reaction that led to dose interruptions was
neutropenia.
AML
The most commonly occurring adverse reactions (>=20%)
of any grade in patients receiving venetoclax in combination with
azacitidine or decitabine in the VIALE-A and M14-358, respectively,
were thrombocytopenia, neutropenia, febrile neutropenia, nausea,
diarrhoea, vomiting, anaemia, fatigue, pneumonia, hypokalaemia, and
decreased appetite, haemorrhage, dizziness/syncope, hypotension,
headache, abdominal pain, and anaemia.
The most frequently reported serious adverse reactions
(≥5%) in patients receiving venetoclax in combination with
azacitidine were febrile neutropenia, pneumonia, sepsis and
haemorrhage. In M14-358, the most frequently reported serious
adverse reactions (≥5%) were febrile neutropenia, pneumonia,
bacteraemia and sepsis.
Discontinuations due to adverse reactions occurred in 24%
of patients treated with venetoclax in combination with azacitidine
in the VIALE-A study, and 26% of patients treated with venetoclax
in combination with decitabine in the M14-358 study,
respectively.
Dosage reductions due to adverse reactions occurred in 2%
of patients in VIALE-A, and in 6% of patients in M14-358.
Venetoclax dose interruptions due to adverse reactions occurred in
72% and 65% of patients, respectively. The most common adverse
reaction that led to dose interruption (>10%) of Venetoclax in
VIALE-A, were febrile neutropenia, neutropenia, pneumonia, and
thrombocytopenia. The most common adverse reactions that led
to dose interruption (≥5%) of venetoclax in M14-358 were febrile
neutropenia, neutropenia/neutrophil count decreased, pneumonia,
platelet count decreased, and white blood cell count
decreased.
Special Populations
Patients with reduced renal function (CrCl <80 mL/min)
may require more intensive prophylaxis and monitoring to reduce the
risk of TLS at initiation and during the dose-titration
phase. Safety in patients with severe renal impairment (CrCl
<30 mL/min) or on dialysis has not been established, and a
recommended dose for these patients has not been
determined.
For patients with severe (Child-Pugh C) hepatic
impairment, a dose reduction of at least 50% throughout treatment
is recommended.
Venclyxto may cause embryo-fetal harm when administered to
a pregnant woman. Advise nursing women to discontinue breastfeeding
during treatment.
This is not a complete summary of all safety
information. See Venclyxto (venetoclax) SmPC at
www.ema.europa.eu. Globally,
prescribing information varies; refer to the individual country
product label for complete information.
About AbbVie in Oncology
At AbbVie,
we are committed to transforming standards of care for multiple
blood cancers while advancing a dynamic pipeline of investigational
therapies across a range of cancer types. Our dedicated and
experienced team joins forces with innovative partners to
accelerate the delivery of potentially breakthrough medicines. We
are evaluating more than 20 investigational medicines in over 300
clinical trials across some of the world's most widespread and
debilitating cancers. As we work to have a remarkable impact on
people's lives, we are committed to exploring solutions to help
patients obtain access to our cancer medicines. For more
information, please
visit www.abbvie.com/oncology and
our Blood Cancer Press Kit
page.
About AbbVie
AbbVie's mission is to
discover and deliver innovative medicines and solutions that solve
serious health issues today and address the medical challenges of
tomorrow. We strive to have a remarkable impact on people's lives
across several key therapeutic areas – immunology, oncology,
neuroscience, and eye care – and products and services in our
Allergan Aesthetics portfolio. For more information about AbbVie,
please visit us at www.abbvie.com. Follow
@abbvie on LinkedIn,
Facebook,
Instagram, X (formerly
Twitter), and
YouTube.
Forward-Looking Statements
Some
statements in this news release are, or may be considered,
forward-looking statements for purposes of the Private Securities
Litigation Reform Act of 1995. The words "believe," "expect,"
"anticipate," "project" and similar expressions and uses of future
or conditional verbs, generally identify forward-looking
statements. AbbVie cautions that these forward-looking statements
are subject to risks and uncertainties that may cause actual
results to differ materially from those expressed or implied in the
forward-looking statements. Such risks and uncertainties include,
but are not limited to, challenges to intellectual property,
competition from other products, difficulties inherent in the
research and development process, adverse litigation or government
action, and changes to laws and regulations applicable to our
industry. Additional information about the economic, competitive,
governmental, technological and other factors that may affect
AbbVie's operations is set forth in Item 1A, "Risk Factors," of
AbbVie's 2022 Annual Report on Form 10-K, which has been filed with
the Securities and Exchange Commission, as updated by its
subsequent Quarterly Reports on Form 10-Q. AbbVie undertakes no
obligation, and specifically declines, to release publicly any
revisions to forward-looking statements as a result of subsequent
events or developments, except as required by
law.
References:
- International Myeloma Foundation. What is Multiple
Myeloma?
https://www.myeloma.org/what-is-multiple-myeloma.
Accessed September
2023.
- Bal S, et al. Am J Cancer Res.
2022;12:2950-2965.
- Clinicaltrials.gov (2023). NCT 03539744: A Study of
Venetoclax and Dexamethasone Compared With Pomalidomide and
Dexamethasone in Subjects With Relapsed or Refractory Multiple
Myeloma (CANOVA).
https://www.clinicaltrials.gov/study/NCT03539744?cond=NCT03539744&rank=1.
Accessed September 2023.
- Multiple Myeloma Research Foundation. Understanding
Multiple Myeloma.
https://themmrf.org/multiple-myeloma/. Accessed
September 2023.
- Cancer.Net. Multiple Myeloma: Statistics.
https://www.cancer.net/cancer-types/multiple-myeloma/statistics.
Accessed September
2023.
- Myeloma UK. Infopack for relapsed and/or refractory
myeloma patients.
https://www.myeloma.org.uk/documents/infopack-for-relapsed-and-or-refractory-myeloma-patients/.
Accessed September
2023.
- Summary of Product Characteristics for VENCLYXTO
(venetoclax). Ludwigshafen, Germany: AbbVie Deutschland GmbH & Co.
KG.
View original
content:https://www.prnewswire.com/news-releases/abbvie-presents-results-from-phase-3-canova-study-of-venetoclax-in-patients-with-relapsed-or-refractory-multiple-myeloma-301942538.html
SOURCE AbbVie