- 60% confirmed ORR% by RECIST 1.1 in HLA-A2(+) in 1L MUM, and
42% confirmed ORR% by RECIST 1.1 in HLA-A2(-) in 1L MUM
- Median PFS of 7.1 months in 1L MUM and 11 months in
hepatic-only MUM
- On further follow-up, ~30% of any-line MUM treated >1 year
and multiple PRs on treatment >2 years, with potential for
further enhancement with ~20% of patients ongoing
treatment
- Historical ORR% and median PFS by other therapies in MUM have
ranged from 0% to 5% and 2 to 3 months, respectively
- 94% ctDNA molecular response rate observed in any-line MUM
- ~70% of MUM patients were HLA-A2(-) based on 149 patients
tested for HLA-A2 status
- 2 of 4 (50%) GNAQ/11 cutaneous melanoma patients on
darovasertib combo observed PRs by RECIST 1.1, with responses on
treatment approximately 600 days
- 50% eye preservation rate (3 of 6 evaluable patients) in
enucleation neoadjuvant IST cohort with darovasertib monotherapy
until maximal benefit
- Synthetic Lethality: Updates on PRs by RECIST 1.1 for
IDE397/MAT2A and IDE161/PARG
- Updated corporate presentation with clinical data updates
on darovasertib, IDE397/MAT2A, and IDE161/PARG is available on
IDEAYA homepage
SOUTH
SAN FRANCISCO, Calif., Oct. 23,
2023 /PRNewswire/ -- IDEAYA Biosciences, Inc.
(Nasdaq:IDYA), a precision medicine oncology company committed to
the discovery and development of targeted therapeutics, announces
clinical data presented at a proffered paper session of the
European Society of Medical Oncology Congress 2023 (ESMO 2023) from
the company's ongoing Phase 2 clinical trial evaluating
darovasertib in combination with crizotinib in patients having
metastatic uveal melanoma (MUM).
"These data contribute to the growing clinical evidence that the
darovasertib and crizotinib combination represents an emerging
treatment advance in metastatic UM, a disease with a historically
poor prognosis," said Meredith
McKean, M.D., MPH, Director, Melanoma and Skin Cancer
Research at Sarah Cannon Research Institute, who is an investigator
on the Phase 2 trial and presented the clinical data at ESMO 2023.
"The manageable safety profile and pronounced efficacy observed in
first-line patients and in all-line hepatic-only patients based on
available data supports the ongoing potentially registrational
Phase 2/3 clinical trial in metastatic UM," concluded Dr.
McKean.
ESMO 2023 Data:
The Phase 2 evaluation of the darovasertib and crizotinib
combination in first-line and pretreated MUM patients showed a
manageable safety profile (n=68) and demonstrated clinical efficacy
in any-line (n=63) and first-line (n=20) MUM patients that appears
superior to current standards of care. The reported Phase 2
clinical data are based on evaluable first-line and 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 for 68
patients as of the data analyses cutoff date of August 22, 2023.
Circulating tumor DNA (ctDNA) molecular responses were
determined based on measured changes in mean allele frequency (MAF)
on-treatment as compared to MAF levels at baseline for a subset of
any-line MUM patients (n=32). Patients whose ctDNA showed a
reduction of greater than 50% MAF following treatment were
characterized as having a ctDNA molecular response.The reported
ctDNA data showed a reduction in MAF in all but one patient.
Significantly, molecular responses were observed in 30 of 32
evaluable patients, reflecting a molecular response rate of 94%.
The determined ctDNA molecular responses were deep and sustained,
with approximately 80% of measured patients having >80%
reduction in MAF. The ctDNA molecular responses correlated
with observed efficacy, including confirmed partial responses (PRs)
as determined by RECIST 1.1.
Clinical efficacy was observed in both human leukocyte antigen
(HLA)-A2 positive (HLA-A2(+)) and HLA-A2 negative (HLA-A2(-))
patients. There were 50 all-line MUM patients with known HLA-A2
status among the 63 patients evaluable for efficacy, with 31 of
these being HLA-A2(-) and 19 being HLA-A2(+). The reported efficacy
data by HLA-A2 serotype was based on a preliminary analysis of
an unlocked database as of August 22,
2023 by investigator review and RECIST 1.1. For HLA-A2(-)
MUM patients, confirmed PRs were observed in 9 of 31 (29% overall
response rate (ORR)) any-line and in 5 of 12 (42% ORR) first-line
patients. For HLA-A2(+) MUM patients, confirmed PRs were also
observed in 6 of 19 (32% ORR) any-line and in 3 of 5 (60% ORR)
first-line patients. With approximately 5.5 months of additional
follow-up from the previous data analysis cut-off date
(March 8, 2023 to August 22, 2023), now approximately 30% of
any-line MUM patients have been on treatment greater than one year
and multiple patients with confirmed PRs by RECIST 1.1 have been on
treatment greater than 24 months, with the potential for further
enhancement on the duration of treatment (DOT) analysis as
approximately 20% (13 out of 63 evaluable patients) of any-line MUM
patients are continuing on treatment. Based on the two-year
progression-free survival (PFS) Kaplan–Meier (KM) curve of the
darovasertib and crizotinib combination in any-line MUM,
the combination provides a promising PFS trend compared to
other therapies, including tebentafusp. Intriguingly, the observed
tail of the PFS curve implies durable benefit in a significant
proportion of patients who remain progression free as far out as 2
years.
HLA-A*02:01 (HLA-A2) status was known in subsets of patients
enrolled in clinical trials evaluating darovasertib. Prevalence of
HLA-A2(+) and HLA-A2(-) in MUM patients was determined from a first
data set of 149 MUM patients treated with darovasertib as
monotherapy or in a combination arm of a clinical trial, and
separately in a second data set of 118 MUM patients treated with
the darovasertib and crizotinib combination.
Collectively, these data demonstrate that approximately 70% of
MUM patients with known HLA-A2 status were HLA-A2(-). These data
include 102 of 149 (68%) patients in the all-treatment subset and
81 of 118 (69%) patients in the darovasertib + crizotinib
combination treatment subset.
The darovasertib and crizotinib combination continued to
demonstrate an overall manageable adverse event profile in MUM
patients (n=68), with a low rate (10%) of drug-related serious
adverse events (SAEs) and limited Grade 4 and Grade 5 SAEs and
discontinuations. Drug-related adverse event (AE), were
predominantly Grade 1 or Grade 2. 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. Five patients (7%) discontinued treatment
with darovasertib and crizotinib combination due to a
drug-related adverse event.
The reported data support IDEAYA's ongoing potentially
registrational Phase 2/3 study (NCT05987332) for potential
accelerated approval of darovasertib and crizotinib for treatment
of first-line HLA-A2(-) MUM patients, where there are currently no
FDA approved therapies.
GNAQ/11 Cutaneous Melanoma:
In the genetically defined GNAQ/GNA11 patient population with
cutaneous melanoma, 3 cohorts of patients treated with
darovasertib, either as monotherapy or in combination with either
binimetinib or crizotinib, have shown preliminary clinical
activity:
- Darovasertib Monotherapy Cutaneous Melanoma Cohort (n=8): 5 of
7 evaluable patients had tumor shrinkage (~71%) with one patient
having a PR and remaining on treatment over 10 months after
previously receiving multiple prior lines of immunotherapy
- Darovasertib plus Binimetinib Cutaneous Melanoma Cohort (n=2):
1 of 2 cutaneous melanoma patients with a PR demonstrated 50% tumor
shrinkage and remained on treatment approximately 600 days after
previously receiving multiple prior lines of immunotherapy
- Darovasertib plus Crizotinib Cutaneous Melanoma Cohort (n=2): 1
of 2 cutaneous melanoma patients had tumor shrinkage of 60% with
one patient having a PR and remaining on treatment (approximately
600 days) after previously receiving multiple prior lines of
immunotherapy
Darovasertib, as monotherapy or in combination with either
binimetinib or crizotinib, has indicated a manageable adverse event
profile in cutaneous melanoma patients with certain drug-related
AEs being reported in certain cohorts. These preliminary clinical
data support initiation of a Phase 2 expansion of the
darovasertib and crizotinib combination in GNAQ/11 metastatic
cutaneous melanoma to advance the darovasertib and crizotinib
combination in this indication where there are currently no FDA
approved therapies in this genetically-defined patient
population.
The GNAQ/11 prevalence in cutaneous melanoma has been
reported at approximately 5% in The Cancer Genome Atlas.
The GNAQ/11 cutaneous melanoma estimated annual incidence is
approximately 5,000 patients in the U.S. and 8,000 patients in the
EU28, and the estimated total prevalence of GNAQ/11 cutaneous
melanoma is approximately 70,000 patients in the U.S. and 110,000
patients in the EU28. It has been reported that approximately 12.5%
to 15% of cutaneous melanoma patients have been reported to develop
metastatic disease, whereas in uveal melanoma, a predominantly
GNAQ/11 mediated cancer, the metastatic rate has been reported at
approximately 50%. In addition, based on several metastatic cancer
patient databases, including Memorial Sloan Kettering Cancer Center
(MSKCC) Impact, we project GNAQ/11 metastatic cutaneous melanoma
has the potential to double or more the annual addressable
metastatic patient population of metastatic uveal melanoma alone.
In addition, GNAQ/11 mutation patients are known to have low tumor
mutational burden making these patients less likely to benefit from
immune checkpoint inhibitor therapies.
Darovasertib Neoadjuvant Monotherapy:
In the ongoing investigator-sponsored Phase 1 clinical trial
(IST) captioned as "Neoadjuvant / Adjuvant trial of Darovasertib in
Ocular Melanoma" (NADOM) being led by principal investigator
Professor Anthony Joshua, MBBS, PhD, FRACP, Head Department of
Medical Oncology, Kinghorn Cancer Centre, St. Vincent's Hospital in
Sydney with participating sites of
Alfred Health and the Royal Victorian Eye and Ear Hospital in
Melbourne, the study reports a
preliminary interim update with an enrollment cut-off as of
July 17, 2023 of seven patients
treated to maximal response in the neo-adjuvant setting (up to 6
months of darovasertib monotherapy in patients who were enrolled
with planned enucleation); 2 patients have confirmed Eye Saved
(i.e., converted to plaque brachytherapy) with a third patient
confirmed as plaque-eligible and is ongoing with darovasertib
neo-adjuvant treatment until maximal benefit; providing 50% overall
eye preservation rate for the evaluable patients. Of the
evaluable patients (6 of 7) treated to maximal benefit, defined as
at least one ultrasound scan, approximately 83% of patients had
tumor shrinkage. Two patients did not complete their treatment to
maximal response; one patient had sub-retinal blood present at
baseline and with lack of shrinkage and visual deterioration,
the patient discontinued treatment after 6 weeks. A non-evaluable
second patient had a Grade 3 drug-related AE of dermatitis and
discontinued treatment before first scan. Two out of four
additional patients after the enrollment cutoff date of
July 17, 2023 are likely plaque
eligible and are continuing darovasertib neoadjuvant therapy until
maximal benefit with 1 patient being enucleated. In total, 11
patients eligible to receive 6 months of neoadjuvant therapy are
enrolled to date in the neoadjuvant UM enucleation cohort
IST.
IDEAYA's Phase 2 company sponsored (neo)adjuvant darovasertib
monotherapy study is observing rapid enrollment to date, with 6 UM
patients now enrolled, including 4 enucleation patients and 2
plaque-therapy patients.
Synthetic Lethality Pipeline:
For IDE397, a potential first-in-class MAT2A inhibitor, we have
observed multiple PRs in the Phase 2 expansion evaluating priority
solid tumor types of squamous NSCLC and bladder cancer. There have
been 8 patients dosed in the Phase 2 expansion in the priority
tumor types, of which 2 have not yet had a first tumor scan
assessment. The PRs include an earlier reported -33% tumor
shrinkage by CT-PET (without contrast) for a squamous NSCLC
patient, and a confirmed PR (47% tumor shrinkage) by RECIST 1.1
with IDE397 in a previously undisclosed tumor type (bladder
cancer). This bladder cancer patient has converted to a complete
response by RECIST 1.1 at the week 18 CT-scan. In addition, of
patients evaluable for ctDNA pre and post treatment, a high ctDNA
molecular response rate of 83% was observed in these MTAP-deletion
priority tumor types. As of the October 13,
2023 cut-off date, in the dose escalation and expansion
phases, we have observed relatively low rates of drug-related
discontinuations and SAEs. The IDE397 and AMG 193 clinical
combination study in MTAP-deletion solid tumors is in ongoing dose
escalation, with an expansion focus on NSCLC.
For IDE161, a potential first-in-class PARG inhibitor, we have
observed multiple PRs by RECIST 1.1. and tumor shrinkage in
priority solid tumor types early in the Phase 1 dose escalation and
at the expansion dose. There have been a total of 7 patients
treated at the expansion dose as of the October 13 2023 cut-off date, of which 2 patients
have not yet had a first scan tumor assessment. The earlier
reported IDE161 partial response at first scan in a BRCA1/2
endometrial cancer patient, is now a confirmed PR by RECIST 1.1 at
the second scan. At the IDE161 expansion dose, we have observed no
drug-related discontinuations or SAEs as of the October 13, 2023 cut-off date.
Updated IDEAYA Corporate Presentation:
An updated corporate presentation reflecting clinical data
updates for darovasertib, and updated clinical efficacy for the
IDE161 and IDE397 programs, including PRs by RECIST 1.1 and ctDNA
molecular responses for IDE397 priority tumor types, will be
available at approximately 6:00am ET
on the IDEAYA Biosciences homepage and at its Investor Relations
portal at approximately 8:30am ET
(https://ir.ideayabio.com/).
About IDEAYA Biosciences
IDEAYA is a 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) expectations regarding the clinical
activity profile and potential advantages of IDEAYA's clinical
programs, (ii) the translation of preliminary clinical trial
results into future clinical trial results, (iii) the enrollment of
clinical trials and (iv) whether the Phase 2/3 clinical
trial will be considered a registrational trial by the FDA.
Such forward-looking statements involve substantial risks and
uncertainties that could cause IDEAYA's 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, serious adverse events, undesirable side effects or
unexpected characteristics of drug development programs, 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, 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
Quarterly Report on Form 10-Q filed on August 10, 2023 and any current and periodic
reports filed with the U.S. Securities and Exchange Commission.
Investor and Media Contact
IDEAYA Biosciences
Andres Ruiz Briseno
Senior Vice President, Head of Finance and Investor Relations
investor@ideayabio.com
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