- Confirmed partial responses by RECIST observed in 4 of 8 (50%
ORR) evaluable First-Line MUM patients and in 11 of 35 (31% ORR)
evaluable Any-Line MUM patients
- Tumor shrinkage observed in 31 of 35 (89%) Any-Line MUM
patients
- Median PFS not yet reached and >5 months in evaluable
First-Line MUM patients; observed median PFS of ~5 months in
evaluable Any-Line MUM patients
- Historical % ORR and median PFS by other therapies in MUM have
been low, ranging from ~0% to 5% ORR and ~2 to 3 months median
PFS
- Proof-of-concept for use in (neo)adjuvant UM with tumor
shrinkage in 5 of 5 ocular lesions, including reductions of ~-74%
and -67%, each with improved visual symptoms
- Total UM and MUM annual incidence in US/EU28 projected at over
13,000 patients, and total UM and MUM prevalence in US/EU28
projected at over 110,000 patients
- Targeting to initiate potential registrational trial for Daro +
Crizo in First-Line MUM in Q1 2023 and company-sponsored trial for
Daro monotherapy in (neo)adjuvant UM in Q4 2022
- Investor webcast and call scheduled for Monday, September 12, 2022, at 8:00am ET
SOUTH
SAN FRANCISCO, Calif., Sept. 11,
2022 /PRNewswire/ -- IDEAYA Biosciences, Inc.
(Nasdaq:IDYA), a synthetic lethality focused precision medicine
oncology company committed to the discovery and development of
targeted therapeutics, announced interim results from its Phase 2
clinical trial evaluating darovasertib and crizotinib synthetic
lethal combination in metastatic uveal melanoma (MUM) patients
(ClinicalTrials.gov Identifier: NCT03947385).
"The confirmed partial responses and high percentage of patients
with tumor shrinkage shown in these interim Phase 2 data are
extremely encouraging for patients with metastatic uveal melanoma.
The 50% overall response rate and greater than 5 months
median progression free survival observed in first-line MUM
patients reflects the potential for a compelling clinical efficacy
profile irrespective of haplotype (HLA-A*02:01) status. The
partial responses shown in first-line and any-line MUM patients are
clinically significant and build on previously-reported results for
any-line MUM patients, now with a larger patient data set," said
Dr. Marlana Orloff, M.D., Associate
Professor, Sidney Kimmel Cancer Center, Jefferson Health.
"The clinical efficacy observed in first-line patients in these
interim Phase 2 data presents an opportunity to pursue a front-line
strategy and provides a rationale for a potential
registration-enabling clinical trial in MUM," said Dr. Matt Maurer, M.D., Vice President, Head of
Clinical Oncology and Medical Affairs, IDEAYA Biosciences.
There are currently no FDA approved therapies for GNAQ and GNA11
solid tumors, and current therapies for MUM have relatively low
objective response rates and short median progression free survival
(PFS), highlighting the high unmet medical need.
Approximately 90% of MUM has either a GNAQ or GNA11 mutation that
activates the protein kinase C (PKC) signaling pathway. The
historical overall response rate (ORR) in MUM clinical trials has
generally been reported with an ORR ranging from approximately 0 to
5%, including: pembrolizumab and tebentafusp (each ~5%); MEK
inhibitor selumetinib in combination with dacarbazine (~3%); and
cMET inhibitor cabozantinib monotherapy (~0%). In addition,
the historical median PFS in MUM clinical trials has been reported
ranging from approximately 2.0 to 2.8 months, including:
tebentafusp (~2.8 months, IMCgp100-102 study); MEK inhibitor
selumetinib in combination with dacarbazine (~2.8 months); and cMET
inhibitor cabozantinib monotherapy (~2.0 months).
Darovasertib (IDE196) is a small molecule, potential
first-in-class protein kinase C (PKC) inhibitor. IDEAYA is
evaluating the synthetic lethal combination of darovasertib and
crizotinib, a small molecule cMET inhibitor, in MUM and other
GNAQ/11 tumors pursuant to a clinical trial collaboration and drug
supply agreement with Pfizer.
Clinical Data Update – Darovasertib and Crizotinib
Combination in MUM
The interim Phase 2 clinical data update
is based on an initial thirty-seven (37) patients enrolled in the
darovasertib and crizotinib combination study at the expansion dose
of 300mg twice-a-day darovasertib and 200mg twice-a-day crizotinib,
as of the data analysis cutoff date of June
26, 2022. Out of the thirty-seven (37) patients enrolled,
there were thirty-five (35) evaluable patients and two (2)
non-evaluable patients. The two (2) non-evaluable patients were
both pretreated and withdrew from the trial prior to the first
scan. Neither of the two non-evaluable patients progressed due to
disease: one (1) patient withdrew consent and one (1) patient
discontinued early due to fatigue. Reported data are
preliminary and based on an unlocked database as of the data
analyses cutoff date, except one confirmatory scan after the data
cutoff date or as otherwise noted. Enrollment in the
darovasertib and crizotinib combination expansion dose cohort of
the clinical trial is ongoing.
The company observed encouraging clinical activity in Phase 2
clinical trial evaluating darovasertib and crizotinib synthetic
lethal combination in metastatic uveal melanoma (MUM) patients in
the expansion dose cohort. These investigator-reviewed data by
RECIST 1.1 include:
- 89% of Patients show Tumor Shrinkage in Any-Line MUM: 31 of 35
evaluable patients showed tumor shrinkage as determined by target
lesion size reduction
- 83% Disease Control Rate (DCR) in Any-Line MUM: 29 of 35
evaluable patients showed stable disease or better as determined by
target lesion size reduction
- 50% Overall Response Rate (ORR) in First-Line MUM: 4 of 8
evaluable patients had a confirmed partial response (PR)
- 31% Overall Response Rate (ORR) in Any-Line MUM: 11 of 35
evaluable patients had a confirmed partial response (PR)
- 43% of Patients with >30% Tumor Reduction in Any-Line MUM:
15 of 35 evaluable patients observed partial responses with >30%
tumor reduction, including 11 confirmed and 4 unconfirmed partial
responses
- Median Study Follow-Up of 6.5 months for First-Line MUM
patients and 7.8 months for Any-Line MUM patients
- Median Duration of Response (DOR) in evaluable First-Line MUM
patients has not yet been reached and 4 of 4 patients with
confirmed PR's in First-Line MUM remain in response; median DOR in
evaluable Any-Line MUM patients has not yet been reached and 7 of
11 patients with confirmed PR's in Any-Line MUM remain in
response
- Median Progression Free Survival (PFS) in First-Line MUM
patients has not yet been reached and is >5 months in evaluable
First-Line MUM patients; median PFS for evaluable Any-Line MUM
patients is ~ 5 months
These data provide robust clinical proof-of-concept for the
efficacy of the darovasertib and crizotinib synthetic lethal
combination treatment.
The darovasertib and crizotinib combination therapy has a
manageable adverse event profile in MUM patients (n=37), with a low
rate of drug-related serious adverse events (SAE's). Patients
reported predominantly Grade 1 or 2 drug-related adverse events:
all patients experienced a drug-related AE, of which 76% were
reported as Grade 1 or 2 and 24% were reported as Grade
3. No patients observed Grade 4 or Grade 5 AE's. One
patient discontinued treatment due to a drug-related adverse event.
The potentially addressable patient population for metastatic
uveal melanoma is estimated to include over 4,000 patients across
US and Europe, based on estimated
annual incidence. As an orally-administered small molecule
precision medicine therapeutic, with demonstrated anti-tumor
activity and manageable adverse event profile, the company
considers the darovasertib and crizotinib combination therapy to
have the potential to be broadly impactful to the MUM patient
population.
IDEAYA is currently targeting to initiate a potential
registration-enabling trial in Q1 2023. The company is
evaluating first-line MUM as a potential registrational regulatory
strategy. As of August 31, 2022,
IDEAYA has enrolled 21 first-line MUM patients at the expansion
dose of the darovasertib and crizotinib combination study.
Darovasertib – (Neo)Adjuvant Uveal Melanoma and Other
Potential Expansion Opportunities
IDEAYA is also evaluating
the potential for darovasertib in other oncology indications,
including as (neo)adjuvant therapy in primary uveal melanoma (UM),
in cMET-driven tumors and in KRAS-mutation tumors.
(Neo)Adjuvant UM represents a significant expansion opportunity
for darovasertib – with a potential annual incidence of
approximately 8,700 patients aggregate in US and Europe.
The company has observed preliminary proof of concept for
potential darovasertib use in the (neo)adjuvant uveal melanoma
setting, including responses of the primary orbital tumor.
Clinical data reflects an observed tumor shrinkage by investigator
review of primary ocular lesions in 5 of 5 (100%) UM or MUM
patients treated as monotherapy or in combination with Crizotinib,
including preliminary observation of tumor reductions in uvea
lesion of two patients after the data cut-off date of August 19, 2022:
- a darovasertib monotherapy patient with metastatic disease and
an intact primary lesion in the eye observed a reduction of
approximately 74% in the eye lesion by PET Standard Uptake Value
(SUV) at an initial scan after approximately 2 weeks on therapy,
with observed improvement in visual symptoms in the affected eye;
this patient remained on therapy for approximately 7 months;
- a darovasertib and crizotinib combination patient with
metastatic disease and an intact primary lesion in the eye observed
tumor shrinkage of approximately 67% by RECIST 1.1 as a
contribution to an overall confirmed PR, with improvement in visual
symptoms in the affected eye; this patient is continuing on therapy
as of approximately 5 months; a second darovasertib and crizotinib
combination MUM patient with an intact primary lesion observed a
reduction of the ocular lesion based on preliminary scan after the
data cut-off date; and
- a darovasertib monotherapy neoadjuvant uveal melanoma patient
with a primary ocular lesion observed a reduction of approximately
20% by RECIST 1.1 at the first scan after 27 days on therapy, with
an observed decrease in ocular vasculature; a second darovasertib
monotherapy neoadjuvant UM patient observed a reduction in the
primary ocular lesion based on preliminary scan after the data
cut-off date; these two patients are enrolled in the NADOM IST and
are continuing on therapy as of approximately 1 month.
"I am excited to explore the potential for darovasertib as a
(neo)adjuvant approach for the treatment of uveal melanoma
patients. The observed clinical experience provides a basis
for clinical investigation to evaluate whether darovasertib, can
improve current primary treatment paradigms, which typically
include radiotherapies and/or enucleation of the eye," said Dr.
Marcus Butler, Medical Oncologist,
Tumor Immunotherapy Program, Melanoma/Skin Oncology Site Lead at
Princess Margaret Cancer Centre in Toronto, Canada, and
Ocular Melanoma Physician Task Force
of Canada Co-Lead.
IDEAYA is supporting St. Vincent's Hospital Sydney Limited,
which has initiated an Investigator Sponsored Trial, or IST,
captioned as the "Neoadjuvant / Adjuvant trial of Darovasertib in
Ocular Melanoma" (NADOM) study, to evaluate darovasertib
monotherapy in a neo-adjuvant and adjuvant setting in primary UM
patients. IDEAYA is targeting initiation of a
company-sponsored clinical trial in Q4 2022 to further evaluate
darovasertib monotherapy in (neo)adjuvant uveal melanoma, and is
evaluating potential near-term clinical endpoints such as vision
and organ preservation.
IDEAYA Investor Webcast and Conference Call
IDEAYA
will host an investor webcast and conference tomorrow morning,
September 12, 2022 at 8:00 am ET, to present darovasertib and
crizotinib Phase 2 interim clinical efficacy and tolerability data,
as well as clinical landscape, potential registrational strategies
and expansion opportunities.
Presenters at the investor webcast and conference call will
include Dr. Marlana Orloff, M.D.,
Associate Professor, Sidney Kimmel Cancer Center, Jefferson Health,
and Dr. Marcus Butler, Medical
Oncologist, Tumor Immunotherapy Program, Melanoma/Skin Oncology
Site Lead at Princess Margaret Cancer Centre
in Toronto, Canada, and Ocular Melanoma Physician Task
Force of Canada Co-Lead, each of whom are key opinion
leaders and clinical investigators. Yujiro S. Hata, President and Chief Executive
Officer, and other members of the IDEAYA management team will also
present.
IDEAYA's darovasertib investor webcast presentation, as well as
an updated corporate presentation, will be available on the
company's website, at its Investor Relations portal
(https://ir.ideayabio.com/) in advance of the investor webcast
presentation at approximately 6:00 am
ET.
Corporate Updates
IDEAYA had cash, cash equivalents
and marketable securities of approximately $324 million as of June
30, 2022, which it currently projects will be sufficient to
fund its planned operations into 2025.
About IDEAYA Biosciences
IDEAYA is a synthetic
lethality focused precision medicine oncology company committed to
the discovery and development of targeted therapeutics for patient
populations selected using molecular diagnostics. IDEAYA's
approach integrates capabilities in identifying and validating
translational biomarkers with drug discovery to select patient
populations most likely to benefit from its targeted
therapies. IDEAYA is applying its research and drug discovery
capabilities to synthetic lethality – which represents an emerging
class of precision medicine targets.
Forward-Looking Statements
This press release contains
forward-looking statements, including, but not limited to,
statements related to (i) timing for initiating potential
registration-enabling trial in MUM, (ii) potential clinical
efficacy profile, and (iii) timing of initiation of a
company-sponsored clinical trial for in Q4 2022 to further evaluate
to evaluate darovasertib in a neo-adjuvant and adjuvant setting in
primary UM patients. Such forward-looking statements involve
substantial risks and uncertainties that could cause IDEAYA's
preclinical and clinical development programs, future results,
performance or achievements to differ significantly from those
expressed or implied by the forward-looking statements. Such risks
and uncertainties include, among others, the uncertainties inherent
in the drug development process, including IDEAYA's programs' early
stage of development, the process of designing and conducting
preclinical and clinical trials, the regulatory approval processes,
the timing of regulatory filings, the challenges associated with
manufacturing drug products, IDEAYA's ability to successfully
establish, protect and defend its intellectual property, the
effects on IDEAYA's business of the worldwide COVID-19 pandemic,
the ongoing military conflict between Russia and Ukraine, and other matters that could affect
the sufficiency of existing cash to fund operations. IDEAYA
undertakes no obligation to update or revise any forward-looking
statements. For a further description of the risks and
uncertainties that could cause actual results to differ from those
expressed in these forward-looking statements, as well as risks
relating to the business of IDEAYA in general, see IDEAYA's recent
Quarterly Report on Form 10-Q filed on August 15, 2022 and any current and periodic
reports filed with the U.S. Securities and Exchange Commission.
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