Arvinas, Inc. (Nasdaq: ARVN) and Pfizer Inc. (NYSE: PFE) today
announced updated clinical data from a Phase 1b combination cohort
evaluating vepdegestrant, an investigational oral PROteolysis
TArgeting Chimera (PROTAC®) estrogen receptor (ER) degrader, in
combination with palbociclib (IBRANCE®). After six months of
additional follow-up, these data are consistent with data presented
at the San Antonio Breast Cancer Symposium (SABCS) in December
2023, and show that vepdegestrant plus palbociclib continue to
demonstrate encouraging clinical activity in heavily pre-treated
patients with a median of four lines of prior therapy with locally
advanced or metastatic ER positive (ER+)/human epidermal growth
factor 2 (HER2) negative (ER+/HER2-) breast cancer. These updated
data were presented at the 2024 European Society for Medical
Oncology (ESMO) Breast Cancer Annual Congress.
“We're encouraged by the clinical activity and safety profile
observed with vepdegestrant in combination with palbociclib in
patients being treated for advanced ER+/HER2- breast cancer,” said
Noah Berkowitz, M.D., Ph.D., Chief Medical Officer at Arvinas. “The
median progression-free survival and duration of response data
suggest a promising therapeutic benefit for these patients
regardless of ESR1 mutation status.”
Vepdegestrant is an investigational PROTAC ER degrader designed
to harness the body’s natural protein disposal system to
specifically target and degrade the estrogen receptor.
Vepdegestrant is being co-developed by Arvinas and Pfizer and is
being evaluated as a monotherapy in the second-line setting in the
ongoing Phase 3 VERITAC-2 trial and in the first-line setting in
combination with palbociclib in the ongoing study lead-in cohort of
the Phase 3 VERITAC-3 trial.
“Pfizer is focused on advancing the next generation of treatment
breakthroughs for people with breast cancer,” said Roger Dansey,
M.D., Chief Development Officer, Oncology, Pfizer. “With
vepdegestrant, we hope to establish a new standard-of-care
endocrine therapy backbone for patients with ER+/HER2- breast
cancer, and the data shared at ESMO Breast Cancer continue to
reinforce its potential.”
“This study evaluating vepdegestrant in combination with
palbociclib among heavily pre-treated patients with advanced
ER+/HER2- metastatic breast cancer is consistent with the clinical
activity, safety, and tolerability outcomes reported at SABCS
2023,” said Erika Hamilton, M.D., Director Breast Cancer Research
and Executive Chair, Breast Cancer Research Executive Committee,
Sarah Cannon Research Institute in Nashville, Tennessee, and a lead
investigator in the vepdegestrant clinical program and presenting
author on the data presentation at ESMO Breast Cancer. “The data
show promise that vepdegestrant could be a potential addition to
current treatment options for this patient population, where there
are significant unmet needs.”
Vepdegestrant + Palbociclib Phase 1b Study The
Phase 1b cohort of the ARV-471-mBC-101 study (NCT04072952) is
designed to assess the safety, tolerability, and anti-tumor
activity of vepdegestrant in combination with palbociclib among 46
patients with heavily pre-treated locally advanced or metastatic
ER+/HER2- breast cancer. Patients in the study received a median of
four prior therapies (median of three in the metastatic setting);
87% were previously treated with a cyclin-dependent kinase 4 and 6
(CDK4/6) inhibitor; 80% were previously treated with fulvestrant;
and 78% were previously treated with chemotherapy, including 48% in
the metastatic setting.
Patients were treated once daily with oral doses of
vepdegestrant at 180 mg (n=2), the recommended Phase 3 dose (RP3D)
of 200 mg (n=21), 400 mg (n=3) or 500 mg (n=20), plus 125 mg of
palbociclib given orally once daily for 21 days, followed by seven
days off treatment in 28-day cycles. Initial data were presented at
SABCS 2023 based on a data cutoff of June 6, 2023.
After six months of additional follow-up with a data cutoff of
December 18, 2023, updated data from the study continue to
demonstrate an encouraging clinical benefit rate, objective
response rate and progression-free survival, and a consistent
safety profile as previously reported at SABCS 2023.
Data presented at the 2024 ESMO Breast Cancer Annual
Congress:
Clinical Benefit Rate (CBR):
- CBR, defined as the rate of confirmed complete response,
partial response, or stable disease ≥24 weeks across all dose
levels (n = 46) was 63% (95% CI: 47.5 - 76.8), with a CBR of 72% in
patients with mutant ESR1 (n=29; 95% CI: 52.8 - 87.3) and a CBR of
53% in patients with wild-type ESR1 (n=15; 95% CI: 26.6 –
78.7).
- CBR in patients dosed at the RP3D of 200 mg (n=21) was 67% (95%
CI: 43.0 - 85.4) with a CBR of 79% in patients with mutant ESR1
(n=14; 95% CI: 49.2 - 95.3) and a CBR of 43% in patients with
wild-type ESR1 (n=7; 95% CI: 9.9 - 81.6)
Objective Response Rate (ORR) and Duration of Response
(DOR):
- The ORR in evaluable patients with
measurable disease at baseline (n=31) was 42% (95% CI: 24.5 - 60.9)
with a median DOR in 13 responders of 14.6 months (95% CI: 9.5 –
not reached). At the RP3D of 200 mg (n=15), the ORR was 53% (95%
CI: 25.6 – 78.7).
- ORR in patients with mutant ESR1 (n=17): 47% (95% CI: 23.0 -
72.2).
- ORR at the RP3D of 200 mg (n=10): 60% (95% CI: 26.2 -
87.8).
- ORR in patients with wild-type ESR1 (n=12): 42% (95% CI: 15.2 -
72.3).
- ORR at the RP3D of 200 mg (n=5): 40% (95% CI: 5.3 - 85.3).
Progression-free Survival (PFS):
- Median PFS (mPFS) based on 27 (59%) events across all dose
levels was 11.2 months (95% CI: 8.2 – 16.5) with a mPFS of 13.7
months (95% CI: 8.2 - NR) in patients with ESR1 mutation (n=29) and
mPFS of 11.1 months (95% CI: 2.8 - 19.3) in patients with wild-type
ESR1 (n=15).
- mPFS in patients dosed at the RP3D of 200 mg (n=21) based on 12
events (57%) was 13.9 months (95% CI: 8.1 - NR) with a mPFS of 13.9
months (95% CI: 8.1 - NR) in patients with ESR1 mutation (n=14) and
mPFS of 11.2 months (95% CI: 1.8 - NR) in patients with wild-type
ESR1 (n=7).
Circulating Tumor DNA (ctDNA):
- Exploratory ctDNA analyses found marked reduction (median
change, −98.9%) in tumor fraction after one treatment cycle (all
dose groups) regardless of ESR1 mutant status and robust
on-treatment decreases in mutant ESR1 ctDNA levels sustained
through cycle 7 (evaluated in patients in 200 mg dose cohort), as
presented in the poster session.
Safety Profile:
- The safety profile of vepdegestrant plus palbociclib was
consistent with what was previously reported with Grade 3/4
treatment-related adverse events (TRAEs) ≥10% of neutropenia (91%)
and decreased white blood cell count (15%); no grade 5 TRAEs or
febrile neutropenia were reported.
- The majority of Grade 4 neutropenia events occurred in the
first cycle of treatment and occurrences of Grade 3/4 neutropenia
decreased following palbociclib dose reductions as described in the
prescribing label.
- The safety profile of vepdegestrant in combination with
palbociclib was otherwise consistent with the profile of
palbociclib and what has been observed in other clinical trials for
vepdegestrant. Three of 46 patients discontinued palbociclib due to
neutropenia including one out of 21 patients treated with the RP3D
of vepdegestrant (200 mg) plus palbociclib 125 mg.
About Vepdegestrant Vepdegestrant is an
investigational, orally bioavailable PROTAC protein degrader
designed to specifically target and degrade the estrogen receptor
(ER) for the treatment of patients with ER positive (ER+)/human
epidermal growth factor receptor 2 (HER2) negative (ER+/HER2-)
breast cancer. Vepdegestrant is being developed as a potential
monotherapy and as part of combination therapy across multiple
treatment settings for ER+/HER2- metastatic breast cancer.
In July 2021, Arvinas announced a global collaboration with
Pfizer for the co-development and co-commercialization of
vepdegestrant; Arvinas and Pfizer will share worldwide development
costs, commercialization expenses, and profits.
The U.S. Food and Drug Administration (FDA) has granted
vepdegestrant Fast Track designation as a monotherapy in the
treatment of adults with ER+/HER2- locally advanced or metastatic
breast cancer previously treated with endocrine-based therapy.
About IBRANCE® (palbociclib) 125 mg tablets and
capsulesIBRANCE is an oral inhibitor of CDKs 4 and
6,1 which are key regulators of the cell cycle that trigger
cellular progression.2,3 In the U.S., IBRANCE is a prescription
medicine indicated for the treatment of adults with HR+,
HER2- advanced or metastatic breast cancer in combination with
an aromatase inhibitor as the first hormonal based therapy; or with
fulvestrant in people with disease progression following hormonal
therapy.
The full U.S. Prescribing Information for the IBRANCE tablets
and the IBRANCE capsules can be
found here and here.
IMPORTANT
IBRANCE®(palbociclib) SAFETY
INFORMATION FROM THE U.S. PRESCRIBING INFORMATION
Neutropenia was the most frequently
reported adverse reaction in PALOMA-2 (80%) and PALOMA-3 (83%). In
PALOMA-2, Grade 3 (56%) or 4 (10%) decreased neutrophil counts were
reported in patients receiving IBRANCE plus letrozole. In PALOMA-3,
Grade 3 (55%) or Grade 4 (11%) decreased neutrophil counts were
reported in patients receiving IBRANCE plus fulvestrant. Febrile
neutropenia has been reported in 1.8% of patients exposed to
IBRANCE across PALOMA-2 and PALOMA-3. One death due to neutropenic
sepsis was observed in PALOMA-3. Inform patients to promptly report
any fever.
Monitor complete blood count prior to starting IBRANCE, at the
beginning of each cycle, on Day 15 of first 2 cycles and as
clinically indicated. Dose interruption, dose reduction, or delay
in starting treatment cycles is recommended for patients who
develop Grade 3 or 4 neutropenia.
Severe, life-threatening, or fatal interstitial
lung disease (ILD) and/or pneumonitis can occur in
patients treated with CDK4/6 inhibitors, including IBRANCE when
taken in combination with endocrine therapy. Across clinical trials
(PALOMA-1, PALOMA-2, PALOMA-3), 1.0% of IBRANCE-treated patients
had ILD/pneumonitis of any grade, 0.1% had Grade 3 or 4, and no
fatal cases were reported. Additional cases of ILD/pneumonitis have
been observed in the post-marketing setting, with fatalities
reported.
Monitor patients for pulmonary symptoms indicative of
ILD/pneumonitis (e.g., hypoxia, cough, dyspnea). In patients who
have new or worsening respiratory symptoms and are suspected to
have developed pneumonitis, interrupt IBRANCE immediately and
evaluate the patient. Permanently discontinue IBRANCE in patients
with severe ILD or pneumonitis.
Based on the mechanism of action, IBRANCE can
cause fetal harm. Advise females of
reproductive potential to use effective contraception during
IBRANCE treatment and for at least 3 weeks after the last dose.
IBRANCE may impair fertility in
males and has the potential to cause genotoxicity.
Advise male patients to consider sperm preservation before taking
IBRANCE. Advise male patients with female partners of reproductive
potential to use effective contraception during IBRANCE treatment
and for 3 months after the last dose. Advise females to inform
their healthcare provider of a known or suspected pregnancy. Advise
women not to breastfeed during IBRANCE
treatment and for 3 weeks after the last dose because of the
potential for serious adverse reactions in nursing infants.
The most common adverse reactions
(≥10%) of any grade reported
in PALOMA-2 for IBRANCE plus letrozole
vs placebo plus letrozole were neutropenia (80% vs 6%), infections
(60% vs 42%), leukopenia (39% vs 2%), fatigue (37% vs 28%), nausea
(35% vs 26%), alopecia (33% vs 16%), stomatitis (30% vs 14%),
diarrhea (26% vs 19%), anemia (24% vs 9%), rash (18% vs 12%),
asthenia (17% vs 12%), thrombocytopenia (16% vs 1%), vomiting (16%
vs 17%), decreased appetite (15% vs 9%), dry skin (12% vs 6%),
pyrexia (12% vs 9%), and dysgeusia (10% vs 5%).
The most frequently reported Grade ≥3 adverse
reactions
(≥5%) in PALOMA-2 for
IBRANCE plus letrozole vs placebo plus letrozole were neutropenia
(66% vs 2%), leukopenia (25% vs 0%), infections (7% vs 3%), and
anemia (5% vs 2%).
Lab abnormalities of any grade occurring
in PALOMA-2 for IBRANCE plus letrozole
vs placebo plus letrozole were decreased WBC (97% vs 25%),
decreased neutrophils (95% vs 20%), anemia (78% vs 42%), decreased
platelets (63% vs 14%), increased aspartate aminotransferase (52%
vs 34%), and increased alanine aminotransferase (43% vs 30%).
The most common adverse reactions
(≥10%) of any grade reported
in PALOMA-3 for IBRANCE plus fulvestrant
vs placebo plus fulvestrant were neutropenia (83% vs 4%),
leukopenia (53% vs 5%), infections (47% vs 31%), fatigue (41% vs
29%), nausea (34% vs 28%), anemia (30% vs 13%), stomatitis (28% vs
13%), diarrhea (24% vs 19%), thrombocytopenia (23% vs 0%), vomiting
(19% vs 15%), alopecia (18% vs 6%), rash (17% vs 6%), decreased
appetite (16% vs 8%), and pyrexia (13% vs 5%).
The most frequently reported Grade ≥3 adverse
reactions
(≥5%) in PALOMA-3 for
IBRANCE plus fulvestrant vs placebo plus fulvestrant were
neutropenia (66% vs 1%) and leukopenia (31% vs 2%).
Lab abnormalities of any grade occurring
in PALOMA-3 for IBRANCE plus fulvestrant
vs placebo plus fulvestrant were decreased WBC (99% vs 26%),
decreased neutrophils (96% vs 14%), anemia (78% vs 40%), decreased
platelets (62% vs 10%), increased aspartate aminotransferase (43%
vs 48%), and increased alanine aminotransferase (36% vs 34%).
Avoid concurrent use of strong CYP3A
inhibitors. If patients must be administered a strong
CYP3A inhibitor, reduce the IBRANCE dose to 75 mg. If the strong
inhibitor is discontinued, increase the IBRANCE dose (after 3-5
half-lives of the inhibitor) to the dose used prior to the
initiation of the strong CYP3A inhibitor. Grapefruit or grapefruit
juice may increase plasma concentrations of IBRANCE and should be
avoided. Avoid concomitant use of strong CYP3A
inducers. The dose of sensitive CYP3A
substrates with a narrow therapeutic index may need
to be reduced as IBRANCE may increase their exposure.
For patients with severe hepatic
impairment (Child-Pugh class C), the recommended dose
of IBRANCE is 75 mg. The pharmacokinetics of
IBRANCE have not been studied in
patients requiring hemodialysis.
About ArvinasArvinas is a clinical-stage
biotechnology company dedicated to improving the lives of patients
suffering from debilitating and life-threatening diseases through
the discovery, development, and commercialization of therapies that
degrade disease-causing proteins. Arvinas uses its proprietary
PROTAC® Discovery Engine platform to engineer proteolysis targeting
chimeras, or PROTAC® targeted protein degraders, that are designed
to harness the body’s own natural protein disposal system to
selectively and efficiently degrade and remove disease-causing
proteins. In addition to its robust preclinical pipeline of PROTAC
protein degraders against validated and “undruggable” targets, the
company has four investigational clinical-stage programs:
vepdegestrant for the treatment of patients with locally advanced
or metastatic ER+/HER2- breast cancer; ARV-766 and bavdegalutamide
for the treatment of men with metastatic castration-resistant
prostate cancer; and ARV-102 for the treatment of patients with
neurodegenerative disorders. For more information, visit
www.arvinas.com.
About Pfizer OncologyAt Pfizer Oncology, we are
at the forefront of a new era in cancer care. Our industry-leading
portfolio and extensive pipeline includes three core mechanisms of
action to attack cancer from multiple angles, including small
molecules, antibody-drug conjugates (ADCs), and bispecific
antibodies, including other immune-oncology biologics. We are
focused on delivering transformative therapies in some of the
world’s most common cancers, including breast cancer, genitourinary
cancer, hematology-oncology, and thoracic cancers, which includes
lung cancer. Driven by science, we are committed to accelerating
breakthroughs to help people with cancer live better and longer
lives.
About Pfizer: Breakthroughs That Change Patients’
LivesAt Pfizer, we apply science and our global resources
to bring therapies to people that extend and significantly improve
their lives. We strive to set the standard for quality, safety and
value in the discovery, development and manufacture of health care
products, including innovative medicines and vaccines. Every day,
Pfizer colleagues work across developed and emerging markets to
advance wellness, prevention, treatments and cures that challenge
the most feared diseases of our time. Consistent with our
responsibility as one of the world's premier innovative
biopharmaceutical companies, we collaborate with health care
providers, governments and local communities to support and expand
access to reliable, affordable health care around the world. For
175 years, we have worked to make a difference for all who rely on
us. We routinely post information that may be important to
investors on our website at www.pfizer.com. In addition, to learn
more, please visit us on www.pfizer.com and follow us on X at
@Pfizer and @Pfizer_News, LinkedIn, YouTube and like us on Facebook
at Facebook.com/Pfizer.
Arvinas Forward-Looking StatementsThis press
release contains forward-looking statements within the meaning of
The Private Securities Litigation Reform Act of 1995 that involve
substantial risks and uncertainties, including statements regarding
; the potential, pending regulatory approval, for vepdegestrant to
address an area of high unmet need; Arvinas’ and Pfizer’s plans
with respect to, the timing and results of ongoing and planned
clinical trials of vepdegestrant, as a monotherapy and in
combination studies; and statements regarding potential therapeutic
benefits of vepdegestrant. All statements, other than statements of
historical facts, contained in this press release, including
statements regarding Arvinas’ strategy, future operations, future
financial position, future revenues, projected costs, prospects,
plans and objectives of management, are forward-looking statements.
The words “anticipate,” “believe,” “estimate,” “expect,” “intend,”
“may,” “might,” “plan,” “predict,” “project,” “target,”
“potential,” “will,” “would,” “could,” “should,” “continue,” and
similar expressions are intended to identify forward-looking
statements, although not all forward-looking statements contain
these identifying words.
Arvinas may not actually achieve the plans, intentions or
expectations disclosed in these forward-looking statements, and you
should not place undue reliance on such forward-looking statements.
Actual results or events could differ materially from the plans,
intentions and expectations disclosed in the forward-looking
statements Arvinas makes as a result of various risks and
uncertainties, including but not limited to: Arvinas’ and Pfizer
Inc.’s (“Pfizer”) performance of the respective obligations with
respect to Arvinas’ collaboration with Pfizer; whether Arvinas and
Pfizer will be able to successfully conduct and complete clinical
development for vepdegestrant; whether Arvinas and Pfizer, as
appropriate, will be able to obtain marketing approval for and
commercialize vepdegestrant on current timelines or at all;
Arvinas’ ability to protect its intellectual property portfolio;
whether Arvinas’ cash and cash equivalent resources will be
sufficient to fund its foreseeable and unforeseeable operating
expenses and capital expenditure requirements; and other important
factors discussed in the “Risk Factors” section of Arvinas’ Annual
Report on Form 10-K for the year ended December 31, 2023 , its
Quarterly Report on Form 10-Q for the quarter ended March 31, 2024,
and subsequent other reports on file with the U.S. Securities and
Exchange Commission. The forward-looking statements contained in
this press release reflect Arvinas’ current views with respect to
future events, and Arvinas assumes no obligation to update any
forward-looking statements, except as required by applicable law.
These forward-looking statements should not be relied upon as
representing Arvinas’ views as of any date subsequent to the date
of this release.
Pfizer Disclosure Notice:The information
contained in this release is as of May 16, 2024. Pfizer assumes no
obligation to update forward-looking statements contained in this
release as the result of new information or future events or
developments.
This release contains forward-looking information about
vepdegestrant, IBRANCE® (palbociclib), a global collaboration
between Pfizer and Arvinas to develop and commercialize
vepdegestrant and Pfizer Oncology, including their potential
benefits, that involves substantial risks and uncertainties that
could cause actual results to differ materially from those
expressed or implied by such statements. Risks and uncertainties
include, among other things, uncertainties regarding the commercial
success of IBRANCE; the uncertainties inherent in research and
development, including the ability to meet anticipated clinical
endpoints, commencement and/or completion dates for clinical
trials, regulatory submission dates, regulatory approval dates
and/or launch dates, as well as the possibility of unfavorable new
clinical data and further analyses of existing clinical data; the
risk that clinical trial data are subject to differing
interpretations and assessments by regulatory authorities; whether
regulatory authorities will be satisfied with the design of and
results from the clinical studies; whether and when any
applications may be filed in any jurisdictions for vepdegestrant
for any potential indications or any other potential indications
for IBRANCE; whether and when regulatory authorities may approve
any potential applications that may be filed for vepdegestrant
and/or IBRANCE in any jurisdictions, which will depend on myriad
factors, including making a determination as to whether the
product’s benefits outweigh its known risks and determination of
the product’s efficacy and, if approved, whether such product will
be commercially successful; decisions by regulatory authorities
impacting labeling, manufacturing processes, safety and/or other
matters that could affect the availability or commercial potential
of vepdegestrant and IBRANCE; whether the collaboration between
Pfizer and Arvinas will be successful; uncertainties regarding the
impact of COVID-19 on Pfizer’s business, operations and financial
results; and competitive developments.
A further description of risks and uncertainties can be found in
Pfizer’s Annual Report on Form 10-K for the fiscal year ended
December 31, 2023 and in its subsequent reports on Form 10-Q,
including in the sections thereof captioned “Risk Factors” and
“Forward-Looking Information and Factors That May Affect Future
Results”, as well as in its subsequent reports on Form 8-K, all of
which are filed with the U.S. Securities and Exchange Commission
and available at www.sec.gov and www.pfizer.com.
Arvinas Contacts
Investor Contact:Jeff
Boyle347-247-5089Jeff.Boyle@arvinas.com
Media Contact:Kathleen Murphy+1 (760)
622-3771Kathleen.Murphy@arvinas.com
Pfizer Contacts
Investor Contact:+1 (212)
733-4848IR@pfizer.com
Media Contact:+1 (212)
733-1226PfizerMediaRelations@pfizer.com
1 IBRANCE® (palbociclib) Prescribing Information. New York.
NY: Pfizer Inc: September 2023.2 Weinberg, RA. pRb and Control of
the Cell Cycle Clock. In: Weinberg RA, ed. The Biology of
Cancer. 2nd ed. New York, NY: Garland Science; 2014:275-329.3
Sotillo E, Grana X. Escape from Cellular Quiescence. In: Enders GH,
ed. Cell Cycle Deregulation in Cancer. New York, NY: Humana Press;
2010:3-22.
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