Arvinas, Inc. (Nasdaq: ARVN), a clinical-stage biotechnology
company creating a new class of drugs based on targeted protein
degradation, today announced promising interim data from the
Company’s Phase 1/2 dose escalation and expansion trial of ARV-766
in men with metastatic castration-resistant prostate cancer
(mCRPC). ARV-766 is an investigational orally bioavailable PROTAC®
protein degrader designed to degrade all clinically relevant
resistance-driving point mutations of the androgen receptor (AR),
including L702H, a mutation associated with resistance to
abiraterone and other AR-pathway novel hormonal agents (NHA). The
company will provide an overview of these data during a fireside
chat at the Jefferies Healthcare Conference today, June 8, 2023, at
11 a.m. ET, which will be available to view in the Investors and
Media section of the Arvinas website.
Data from the Phase 1/2 dose escalation and expansion trial show
that ARV-766 was well-tolerated and demonstrated promising activity
in a heavily pre-treated, post-NHA, all-comers patient
population:
- 42% of patients with AR ligand
binding domain (LBD) mutations achieved PSA50
- In all patients with L702H
mutations, 3 of 5 achieved PSA50
- In patients with co-occurring
T878/H875/L702 mutations, 3 of 3 achieved PSA50
- RECIST (Response Evaluation Criteria
in Solid Tumors) partial responses were observed:
- Of four RECIST-evaluable patients
with AR LBD mutations, one achieved a confirmed partial response,
and one achieved an unconfirmed partial response
- ARV-766 has been well tolerated and
the majority of treatment-related adverse events (TRAEs) have been
Grade 1 or 2, with no Grade ≥4 TRAEs and no dose limiting
toxicities
- Low rates of discontinuation (1 of
47) and dose reductions (2 of 47)
“Tumor resistance mechanisms such as AR LBD mutations are
increasing with earlier use of NHAs, leaving limited treatment
options for men with prostate cancer in the post-NHA setting,” said
John Houston, Ph.D., president and chief executive officer at
Arvinas. “It’s very exciting to see ARV-766 show signs of efficacy
in these late-line patients, including in patients with L702H
mutations. Our AR franchise now includes data showing two active
clinical compounds with good tolerability profiles and the
potential to address high unmet need in castrate-resistant and
castrate-sensitive prostate cancer.”
“The patients in this trial received extensive prior therapy for
mCRPC and had limited alternative treatment options,” said Ron
Peck, M.D., chief medical officer at Arvinas. “These data increase
our confidence in our ability to bring innovative treatment options
to a patient population with significant unmet need. We are excited
by the progress in our AR franchise and the potential for
bavdegalutamide and ARV-766 to address settings across the
continuum of prostate cancer and potentially other AR-driven
cancers.”
About the Phase 1/2 dose escalation and expansion trial
of ARV-766
The Phase 1/2 dose escalation and expansion trial of ARV-766 is
a seamless trial that includes a Phase 1 dose escalation portion
and a Phase 2 dose expansion portion (data cutoff: April 2023). The
Phase 1 dose escalation of ARV-766 was designed to assess its
safety, tolerability, and pharmacokinetics (PK) in men with mCRPC
who have progressed on standard of care therapies, as well as to
identify recommended Phase 2 doses for further dose optimization.
The Phase 2 expansion cohort is designed to evaluate the antitumor
activity of ARV-766 at the two recommended doses (100 mg and 300
mg) and determine the appropriate dose for future development.
In both the Phase 1 dose escalation and Phase 2 dose expansion,
100% of patients were previously treated with at least one or more
novel hormonal agents. Patients had a median of 4 prior lines of
therapy in the Phase 1 trial and 5 prior lines of therapy in the
Phase 2 trial. Multiple prior therapies have been associated with a
decreased responsiveness to AR-directed therapies and an increase
in tumor heterogeneity.
AR LBD mutations were present in 28% (13 of 47) of patients’
tumors in the Phase 1/2 trial as determined by plasma DNA
analysis.
Efficacy
Across the Phase 1 and interim Phase 2 data, ARV-766 achieved a
42% PSA50 in patients with AR LBD mutations. Three of 5 patients
with AR L702H mutations achieved PSA50; the three responding AR
L702H patients had co-occurring T878/H875 mutations.
Two of 4 RECIST-evaluable patients with tumors harboring AR LBD
mutations had a best observed response of partial response (1
confirmed partial response, 1 unconfirmed partial response).
Safety
ARV-766 has been well tolerated to date and the majority of
TRAEs in the Phase 1 dose escalation data and the Phase 2 interim
dose expansion data were Grade 1/2. There have been no Grade ≥4
TRAEs. None of the 34 patients treated in the Phase 1 dose
escalation portion experienced a dose limiting toxicity. The most
frequent TRAEs (>10%) in Phase 1 have been fatigue, nausea, and
diarrhea. At the time of data cutoff, no TRAE of >10% frequency
was observed in Phase 2.
Forty-seven (47) patients across the Phase 1 and 2 trials were
evaluable for safety. No patients discontinued treatment of ARV-766
due to TRAEs in Phase 1, and one patient discontinued treatment due
to a TRAE in Phase 2. Two of 47 patients (both in Phase 1) were
dose reduced due to TRAEs.
Based on pharmacokinetics, tolerability, and signals of activity
in the Phase 1 dose escalation trial, 100 mg and 300 mg, once
daily, were selected as the recommended Phase 2 expansion doses.
The Phase 2 expansion (N = ~80) began enrolling in October
2022.
Anticipated 2023AR Franchise (bavdegalutamide/ARV-766)
Milestones
- Submit and present updated data,
including radiographic progression free survival, from the ongoing
Phase 1/2 trial with bavdegalutamide at a medical congress (2H
2023).
- Initiate a global Phase 3 trial with
bavdegalutamide in mCRPC (2H 2023).
- Complete enrollment in the Phase 1b
combination study with bavdegalutamide plus abiraterone (2H
2023).
- Initiate a Phase 1b/2 trial with
ARV-766 in combination with abiraterone in patients who have not
previously received novel hormonal agents (2H 2023).
About bavdegalutamide (ARV-110) and
ARV-766Bavdegalutamide (ARV-110) and ARV-766 are
investigational orally bioavailable PROTAC® protein degraders
designed to selectively target and degrade the androgen receptor
(AR). Bavdegalutamide and ARV-766 are being developed as potential
treatments for men with prostate cancer. Preclinically, both
investigational agents have demonstrated activity in models of wild
type tumors in addition to tumors with AR mutation or
amplification, both common mechanisms of resistance to currently
available AR-targeted therapies.
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 three investigational clinical-stage programs in
development: bavdegalutamide and ARV-766 for the treatment of men
with metastatic castration-resistant prostate cancer; and
vepdegestrant (ARV-471) for the treatment of patients with early
and locally advanced or metastatic ER positive/human epidermal
growth factor receptor 2 (HER2) negative (ER+/HER2-) breast cancer.
For more information, visit www.arvinas.com.
Forward-Looking Statements This 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 advantages and therapeutic benefits of
bavdegalutamide (ARV-110) and ARV-766, the development and
regulatory status of our product candidates, such as statements
with respect to the potential of our lead product candidates
bavdegalutamide and ARV-766, the initiation of and timing of the
timing of clinical trials, including the timing to complete
enrollment, as well as the presentation and/or publication of data
from those trials and plans for registration for our product
candidates, the potential utility of our technology, the potential
commercialization of any of our product candidates, and the
sufficiency of our cash resources. All statements, other than
statements of historical facts, contained in this press release,
including statements regarding our 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.
We may not actually achieve the plans, intentions or
expectations disclosed in our forward-looking statements, and you
should not place undue reliance on our forward-looking statements.
Actual results or events could differ materially from the plans,
intentions and expectations disclosed in the forward-looking
statements we make as a result of various risks and uncertainties,
including but not limited to: whether we will be able to
successfully conduct and complete development
for bavdegalutamide and ARV-766, whether we initiate and
complete clinical trials for our product candidates and receive
results from our clinical trials on our expected timelines or at
all; obtain marketing approval for and commercialize
bavdegalutamide and ARV-766 and our other product candidates on our
current timelines or at all; whether our cash and cash
equivalent resources will be sufficient to fund our foreseeable and
unforeseeable operating expenses and capital expenditure
requirements; and other important factors discussed in the “Risk
Factors” section of our Annual Report on Form 10-K for the year
ended December 31, 2022 and subsequent other reports on file with
the Securities and Exchange Commission. The forward-looking
statements contained in this press release reflect our current
views with respect to future events, and we assume 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 our views as of any date subsequent to
the date of this release.
ContactsInvestors:Jeff Boyle+1
(347) 247-5089Jeff.Boyle@arvinas.com
Media:Kirsten Owens+1 (203)
584-0307Kirsten.Owens@arvinas.com
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