- Confirmed overall response rate (ORR) of 45%, disease control
rate (DCR) of 90% and median PFS of ~7 months in 20 evaluable
First-Line MUM patients
- Based on FDA meeting, initiating Phase 2/3 registrational trial
in Q2 2023 in First-Line HLA-A2 negative MUM, with median PFS as
primary endpoint for potential accelerated approval
- Confirmed overall response rate (ORR) of 30%, disease control
rate (DCR) of 87% and median PFS of ~7 months in 63 evaluable
Any-Line MUM patients
- Confirmed overall response rate (ORR) of 35%, disease control
rate (DCR) of 100% and median PFS of ~11 months in 20 evaluable
Hepatic-Only MUM patients
- Historical % ORR and median PFS by other therapies in MUM have
been low, ranging from ~0% to 5% confirmed ORR and ~2 to 3 months
median PFS
- Neoadjuvant PoC: Ocular tumor shrinkage in 9 of 9 (100%) UM /
MUM patients, including a neoadjuvant UM patient with a partial
response at 1 month and a second neoadjuvant UM patient who was
spared enucleation with ~80% tumor shrinkage at 4 months
- Investor webcast and call with management and key opinion
leaders scheduled for Monday, April 24,
2023, at 8:00 am ET
SOUTH
SAN FRANCISCO, Calif., April 23,
2023 /PRNewswire/ -- IDEAYA Biosciences, Inc.
(Nasdaq: IDYA), a precision medicine oncology company committed to
the discovery and development of targeted therapeutics, announced
further interim results from its Phase 2 clinical trial evaluating
darovasertib and crizotinib combination in metastatic uveal
melanoma (MUM) patients (ClinicalTrials.gov Identifier:
NCT03947385).
"The observed efficacy in first-line metastatic uveal melanoma
patients – including confirmed ORR of 45% and median PFS of ~ 7
months – is clinically significant and represents a potential
paradigm shift for treating MUM patients. The interim data
for the darovasertib and crizotinib combination treatment in MUM
suggests a compelling clinical efficacy and tolerability profile,"
said Dr. Meredith McKean, M.D., MPH,
Director, Melanoma and Skin Cancer Research at Sarah Cannon
Research Institute.
"These clinical data, considered with the FDA's guidance from
our recent Type C meeting, provides IDEAYA with a registrational
trial design in first-line HLA-A2 negative MUM patients which
includes a path to potential accelerated approval based on median
PFS as the primary endpoint," said Dr. Darrin Beaupre, M.D., Ph.D., Chief Medical
Officer, IDEAYA Biosciences.
There are currently no FDA approved therapies for MUM patients
with HLA-A2*02:01 (HLA-A2) negative serotype. Current
therapies for MUM have relatively low confirmed overall response
rates and short median progression free survival (PFS),
highlighting the high unmet medical need. The historical
overall response rate (ORR) in MUM clinical trials has generally
been reported with a confirmed ORR ranging from approximately 0% to
5%. The historical median PFS in MUM clinical trials has been
reported ranging from approximately 2 to 3 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 pursuant to a
clinical trial collaboration and drug supply agreement with
Pfizer.
Clinical Data Update – Darovasertib and Crizotinib
Combination in MUM
The company observed encouraging clinical activity in the Phase
2 clinical trial evaluating the darovasertib and crizotinib
combination in first-line and any-line MUM patients. The
reported Phase 2 clinical data are based on twenty (20) evaluable
first-line and sixty-three (63) evaluable any-line patients
enrolled in the darovasertib and crizotinib combination study at
the expansion dose of 300 mg twice-a-day darovasertib and 200 mg
twice-a-day crizotinib as of September 22,
2022. Reported data are preliminary and based on
investigator review from an unlocked database as of the data
analyses cutoff date of March 8,
2023. Enrollment in the darovasertib and crizotinib
combination expansion dose cohort of the Phase 2 clinical trial is
ongoing.
In the twenty (20) evaluable first-line MUM patients in the
expansion cohort, the investigator-reviewed data by RECIST 1.1
include:
- 45% confirmed Overall Response Rate (ORR) in First-Line MUM: 9
of 20 evaluable patients had a confirmed partial response (PR)
- 90% Disease Control Rate (DCR) in First-Line MUM: 18 of 20
evaluable patients showed disease control, including 9 confirmed
PRs, 1 unconfirmed PR and 8 stable disease
- ~7 months median Progression Free Survival (PFS) in First-Line
MUM
In the sixty-three (63) evaluable any-line MUM patients at the
expansion dose, the investigator-reviewed data by RECIST 1.1
include:
- 30% confirmed Overall Response Rate (ORR) in Any-Line
MUM: 19 of 63 evaluable patients had a confirmed partial
response (PR); the Any-Line MUM patients were heavily pre-treated,
with 63% of patients having received 1 or more prior lines of
treatment and 43% of patients having received 2 or more prior lines
of treatment in the metastatic setting
- 87% Disease Control Rate (DCR) in Any-Line MUM: 55 of 63
evaluable patients showed disease control, including 19 confirmed
PRs, 4 unconfirmed PRs and 32 stable disease
- ~7 months median Progression Free Survival (PFS) in Any-Line
MUM
- Observed median PFS increased versus median PFS of ~5 months
previously reported in September 2022
with thirty-five (35) evaluable Any-Line MUM patients
There were twenty (20) evaluable hepatic-only MUM patients,
including first-line and pre-treated patients with only hepatic
metastases, for whom the investigator-reviewed data by RECIST 1.1
include:
- 35% confirmed Overall Response Rate (ORR) in Hepatic-Only MUM:
7 of 20 evaluable patients had a confirmed partial response
(PR)
- 100% Disease Control Rate (DCR) in Hepatic-Only MUM: 20 of 20
evaluable patients showed disease control, including 7 confirmed
PRs, 1 unconfirmed PR and 12 stable disease
- ~11 months median Progression Free Survival (PFS) in
Hepatic-Only MUM
These data demonstrate robust clinical efficacy of the
darovasertib and crizotinib combination in first-line and any-line
MUM patients.
The darovasertib and crizotinib combination has a manageable
adverse event profile in MUM patients (n=68), with a low rate of
drug-related serious adverse events (SAEs). Patients reported
predominantly Grade 1 or 2 drug-related adverse events (AEs): 31%
of patients reported at least one Grade 3 AE; no patients observed
a Grade 4 AE; and one patient observed a Grade 5 AE. Four (6%)
patients discontinued treatment with either darovasertib or
crizotinib due to a drug-related adverse event.
FDA Guidance in Type C Meeting Supports Initiation of
Potential Registrational Trial
IDEAYA is targeting to initiate a potential
registration-enabling Phase 2/3 clinical trial in Q2 2023 in
first-line HLA-A2 negative MUM patients. The Phase 2/3
clinical trial design incorporates guidance and feedback from the
FDA following a recent Type C meeting.
The protocol includes an integrated Phase 2/3 open-label
study-in-study design in first-line MUM patients with an
HLA-A*02:01 negative serotype. The clinical trial design
employs a Phase 2 portion with median PFS as a primary endpoint for
potential accelerated approval. Patients enrolled in
Phase 2 will continue on treatment within the same clinical trial
and will be considered together with additional enrolled
patients to evaluate OS in support of a potential Phase 3
registrational trial.
In the Phase 2 portion of the clinical trial, approximately 230
patients will be randomized on a 2:1 basis for treatment with the
darovasertib and crizotinib combination in the treatment arm or
investigators choice in the control arm, selected from a
combination of ipilimumab (ipi) and nivolumab (nivo), PD1-targeted
monotherapy or DTIC. The treatment arm of the Phase 2 portion
includes a nested study to confirm the move forward combination
dose for the integrated Phase 2/3 clinical trial – including
cohorts at the Phase 2 expansion doses of (i) darovasertib 300 mg
BID + crizotinib 200 mg BID and (ii) darovasertib 200 mg BID +
crizotinib 200 mg BID. Under the nested study design,
patients enrolled in the cohort at the move forward dose will be
included within the Phase 2/3 registrational clinical trial.
The Phase 2 portion of the clinical trial contemplates an efficacy
and safety data set of approximately 200 patients randomized 2:1
with the treatment arm at the move forward dose to support a
potential accelerated approval based on median PFS by blinded
independent central review (BICR) as a primary endpoint.
Patients enrolled in Phase 2 at the selected dose would continue
on treatment and be included in the Phase 3 study analysis,
supplemented by enrollment of approximately 120 additional patients
into the Phase 3 portion of the clinical trial with 2:1
randomization on the same basis as the Phase 2 portion.
Efficacy data from the Phase 3 could support potential approval
using median OS as a primary endpoint.
Clinical Data Update – Darovasertib in (Neo)Adjuvant Primary
UM
The company observed further evidence of encouraging clinical
activity for darovasertib as neoadjuvant therapy in primary uveal
melanoma (UM), including responses in primary ocular tumor
lesions. Data was reported from an ongoing investigator
sponsored trial (IST) evaluating darovasertib in (neo)adjuvant
uveal melanoma, from compassionate use protocol(s) and from the
company's Phase 1/2 clinical trial evaluating darovasertib as
monotherapy and in combination with crizotinib. Best ocular
tumor response is reported based on maximal percentage reduction in
measured apical height or longest basal diameter.
Collectively, these data further substantiate clinical proof of
concept (PoC) for the use of darovasertib in the (neo)adjuvant
uveal melanoma setting:
- Ocular tumor shrinkage by investigator review in 9 of 9 (100%)
UM (n=6) or MUM (n=3) patients treated as monotherapy or in
combination with crizotinib, including a neoadjuvant UM patient
treated with darovasertib with a partial response at 1 month, and a
second neoadjuvant UM patient treated with the darovasertib and
crizotinib combination with ~80% ocular tumor shrinkage at 4 months
who was spared enucleation, as described below.
- A UM patient who was already blind in one eye from vascular
disease developed a large uveal melanoma lesion in his other eye
and sought neoadjuvant treatment with a goal to avoid enucleation
and potentially preserve vision in the affected eye to prevent
blindness. This patient, who remains on therapy, was treated
with darovasertib and crizotinib combination under a compassionate
use protocol. The preliminary clinical data showed:
-
- observed ~80% ocular tumor shrinkage after 4 months of
treatment and remains on therapy
- avoided enucleation of the affected eye, which we believe to be
a first reported case of systemic neoadjuvant therapy resulting in
eye preservation
- prompt responsiveness to treatment, including progressive tumor
shrinkage, as determined by investigator measurement of tumor
apical height, over each month of treatment, including
approximately 30% ocular tumor shrinkage after 1 month, with
ocular lesion size reduced to approach threshold for plaque
brachytherapy, and further ocular tumor shrinkage to ~50% after 2
months, ~70% after 3 months and ~80% after 4 months of
treatment
- improved vision following course of treatment and treatment of
a severe cataract: pretreatment vision score was 6/120, where 6/60
is legally blind; post-treatment vision score was 6/5, reflecting a
greater than 20-fold improvement and resulting in better than
normal vision. Vision scoring was based on AU meter measurement
system: 6/6 m = 20/20 ft (normal vision).
"These additional clinical data underscore the potential for
darovasertib as a (neo)adjuvant approach for the treatment of uveal
melanoma patients. If clinically validated, this approach
could significantly improve current primary treatment paradigms,
which typically include radiotherapies and/or enucleation of the
eye," said Prof. Anthony Joshua,
MBBS Ph.D. FRACP, Head of the Department of Medical Oncology,
Kinghorn Cancer Centre, St Vincent's Hospital/Garvan Medical
Research Institute, Sydney,
Australia.
IDEAYA is initiating a company-sponsored clinical trial to
evaluate darovasertib as monotherapy in (neo)adjuvant uveal
melanoma and is evaluating potential near-term clinical neoadjuvant
endpoints such as organ preservation (avoiding enucleation) for
large ocular tumors and reduction in radiation dose and/or vision
preservation for small or medium ocular tumors.
IDEAYA is also supporting St. Vincent's Hospital Sydney Limited,
which has initiated an ongoing IST captioned as "Neoadjuvant /
Adjuvant trial of Darovasertib in Ocular Melanoma" (NADOM)
(NCT05187884), to evaluate darovasertib monotherapy in a
neoadjuvant and adjuvant setting in primary UM patients.
Addressable Patient Population in MUM and UM
The potentially addressable patient population for metastatic
uveal melanoma is estimated to include approximately 4,500 patients
across U.S. and Europe, based on
estimated annual incidence, and approximately 14,000 patients in
total prevalence in the US and Europe. (Neo)Adjuvant UM
represents a significant expansion opportunity for darovasertib –
with a potential annual incidence of approximately 8,700 patients
aggregate in U.S. and Europe, and
approximately 100,000 patients in total prevalence in the U.S. and
Europe.
IDEAYA owns or controls all commercial rights in darovasertib,
including in MUM and in UM, subject to certain economic obligations
pursuant to the Novartis exclusive, worldwide license.
IDEAYA Investor Webcast and Conference Call
IDEAYA will host an investor webcast and conference tomorrow
morning, Monday, April 24, 2023 at
8:00 am Eastern Time (ET), to present
the further darovasertib and crizotinib Phase 2 clinical efficacy
and tolerability data in metastatic uveal melanoma, and the
potential registrational clinical trial design based on guidance
and feedback from the recent FDA Type C meeting. The company
will also provide a clinical data update for darovasertib in
neoadjuvant uveal melanoma.
Presenters at the investor webcast and conference call will
include Dr. Meredith McKean, M.D.,
MPH, Director, Melanoma and Skin Cancer Research at Sarah Cannon
Research Institute, Prof. Anthony
Joshua, MBBS Ph.D. FRACP, Head of the Department of Medical
Oncology, Kinghorn Cancer Centre, St Vincent's Hospital/Garvan
Medical Research Institute, Sydney,
Australia, and Prof. Mark
Shackleton, MBBS, Ph.D., FRACP, Professor of Oncology,
Monash University, Director of Oncology, Alfred Health,
Chair, Melanoma and Skin Cancer Trials,
Melbourne, Australia, each of whom are key opinion leaders and
clinical investigators. Yujiro S.
Hata, Chief Executive Officer of IDEAYA Biosciences, and
Darrin Beaupre, M.D., Ph.D., Chief
Medical Officer of IDEAYA Biosciences, will also present.
IDEAYA's darovasertib investor webcast presentation, as well as
an updated corporate presentation, which incorporates the updated
darovasertib clinical data as well as IDE397, IDE161 and Werner
Helicase program updates from AACR 2023, 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 $373 million as of December 31, 2022, which it currently projects
will be sufficient to fund its planned operations into 2026.
About IDEAYA Biosciences
IDEAYA is a 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
Certain statements
contained herein are forward-looking statements reflecting the
current beliefs and expectations of management made pursuant to the
safe harbor provisions of the Private Securities Litigation Reform
Act of 1995. These statements relate to future events and involve
known and unknown risks, uncertainties and other factors that may
cause the actual results, levels of activity, performance or
achievements of IDEAYA Biosciences, Inc. (the "Company") or its
industry to be materially different from those expressed or implied
by any forward-looking statements. In some cases, forward-looking
statements can be identified by terminology such as "may," "will,"
"could," "would," "should," "expect," "plan," "anticipate,"
"intend," "believe," "estimate," "predict," "potential" or other
comparable terminology. All statements other than statements of
historical fact could be deemed forward-looking, including, but not
limited to, statements related to (i) the timing for initiation of
and trial design for the darovasertib and crizotinib combination
Phase 2/3 registrational trial, (ii) the timing and content of the
IDEAYA investor webcast and conference call, (iii) the potential
clinical benefit of darovasertib as a (neo)adjuvant therapy, and
(iv) the potentially addressable patient population for MUM and
(neo)adjuvant UM. The company has based these forward-looking
statements on its current expectations, assumptions, estimates and
projections. While the Company believes these expectations,
assumptions, estimates and projections are reasonable, such
forward-looking statements are only predictions and involve known
and unknown risks and uncertainties, many of which are beyond the
Company's control. Such risks and uncertainties include, among
others, the uncertainties inherent in the drug development process,
including the Company'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, the Company's ability to successfully establish, protect
and defend its intellectual property, the effects on the Company'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. These and other important factors may cause
actual results, performance or achievements to differ materially
from those expressed or implied by these forward-looking
statements. The forward-looking statements contained herein are
made only as of the date hereof. 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
the Company's periodic filings with the Securities and Exchange
Commission, including the Company's Annual Report on Form 10-K for
the year ended December 31, 2022 and
any current and periodic reports filed thereafter. Except as
required by law, the Company assumes no obligation and does not
intend to update these forward-looking statements or to conform
these statements to actual results or to changes in the Company's
expectations.
Investor and Media Contact
IDEAYA Biosciences
Paul Stone
Senior Vice President and Chief Financial Officer
investor@ideayabio.com
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