- ~33% ORR by RECIST 1.1: 1 CR +
8 PRs out of 27 evaluable heavily pre-treated (median 2-3 prior
lines, ranging from 1-7) MTAP-deletion UC and NSCLC patients
- 9 of 9 responses have confirmed by RECIST 1.1 (5 confirmed
responses out of 18 evaluable patients reported on July 8, 2024, IDE397 webcast)
- MTAP-deletion UC: 40% (4 of 10) confirmed ORR and 3 pts on treatment >250 days
- MTAP-deletion SqNSCLC: ~38% (3 of 8) confirmed ORR and 4 pts on treatment >200 days
- Multiple PRs with genetic co-alterations, including
MTAP-deletion and KRAS G12D mutation in NSCLC, and MTAP-deletion
and FGFR-TACC3 fusion in UC
- Median DOT not yet reached and >6.2 months, and median TTR
~2.7 months
- ~81% (17 of 21) ctDNA MRR, and high DCR of 93% (25 of 27 with
SD or better)
- AE Profile: No drug-related SAEs or discontinuations at 30 mg
once-a-day expansion dose
- Targeting expansion of Phase 1/2 study of IDE397 in combination
with Trodelvy® in MTAP-deletion UC in Q4 2024; patient
case study of PR by RECIST 1.1 and rapid >95% ctDNA reduction of
combination will be presented at ENA 2024
- IDE397 demonstrated deep and durable regressions in combination
with PRMT5 inhibitors BMS-986504 and AMG 193 in preclinical
models
SOUTH
SAN FRANCISCO, Calif., Oct. 25,
2024 /PRNewswire/ -- IDEAYA Biosciences, Inc.
(Nasdaq: IDYA), a precision medicine oncology company committed to
the discovery and development of targeted therapeutics, announces
Phase 1 expansion data for IDE397 in methylthioadenosine
phosphorylase (MTAP)-deletion urothelial cancer (UC) and non-small
cell lung cancer (NSCLC) patients as a late breaker abstract (LBA)
oral presentation at the 36th edition of the
EORTC-NCI-AACR Symposium (ENA 2024) in Barcelona, Spain. In addition, IDEAYA had
additional poster presentations at ENA 2024 highlighting
preclinical data for the MAT2A and PARG programs. IDE397 is a
potent and selective potential first-in-class methionine
adenosyltransferase 2 alpha (MAT2A) inhibitor in Phase 2 clinical
trials for the treatment of MTAP-deletion solid tumors.
"We are excited by the clinical efficacy and safety profile
observed with the potential first-in-class MAT2A inhibitor IDE397
at the 30mg once-a-day RP2D, including multiple confirmed responses
observed as a monotherapy agent in non-small cell lung cancer and
urothelial cancer patients with MTAP-deletion. In addition, at the
30mg once-a-day expansion dose, we observed a manageable safety
profile with no drug-related serious adverse events or
discontinuations. These data support potential combination
development," said Dr. Benjamin
Herzberg, M.D., Assistant Professor of Medicine, Columbia
University.
"The clinical data update from the late breaker oral
presentation at ENA 2024 provides further clinical proof-of-concept
for IDE397 in the setting of MTAP-deletion urothelial cancer and
non-small cell lung cancer to deliver a high disease control rate
and confirmed RECIST responses, with an overall manageable adverse
event profile," said Darrin M.
Beaupre, M.D., Ph.D., Chief Medical Officer, IDEAYA
Biosciences.
"IDE397 is rapidly advancing as a monotherapy agent in
MTAP-deletion urothelial cancer and non-small cell lung cancer.
Next, we are well positioned to advance our broad and potential
first-in-class IDE397 rational combination strategy, including the
targeted expansion in the fourth quarter with Trodelvy®
in urothelial cancer, the ongoing combination with AMG 193 with
targeted expansion in NSCLC, combinations with IDEAYA's internal
MTAP-deletion pipeline that includes a targeted development
candidate by year-end, among others," said Yujiro S. Hata, President and Chief Executive
Officer, IDEAYA Biosciences.
There are currently no FDA-approved therapies for patients with
MTAP-deletion solid tumors, highlighting the unmet medical need.
The priority MTAP-deletion solid tumor types for the IDE397 Phase
1/2 monotherapy program are UC and NSCLC. MTAP-deletion has been
reported at over 15% in NSCLC and over 25% in UC, based on The
Cancer Genome Atlas (TCGA) database. We estimate that the annual
incidence of MTAP-deletion in the U.S. in UC and NSCLC is
approximately 48,000 patients, based on the 2024 Surveillance,
Epidemiology, and End Results (SEER) database. In addition, there
are several potential expansion MTAP-deletion solid tumor types
that are also being considered for monotherapy and combination
development, including pancreatic, gastric, esophageal, and head
and neck cancer, among others. Based on the TCGA database,
MTAP-deletion in pancreatic cancer has been reported in more than
20% of patients, representing a U.S. annual incidence of
approximately 14,000 patients.
ENA 2024 Clinical Data Update – IDE397 Phase 2 Expansion in
Subjects with MTAP-Deletion UC and NSCLC
The company
observed encouraging clinical activity at the 30 mg once-a-day (QD)
Recommended Phase 2 Dose (RP2D) in its Phase 1 clinical trial
evaluating its potential first-in-class MAT2A inhibitor IDE397 in
heavily pre-treated MTAP-deletion UC and NSCLC patients. The
patients evaluated had a median of two (2) to three (3) prior
lines-of-therapy, ranging from one (1) to seven (7). The reported
Phase 1 clinical expansion data are based on twenty-seven (27)
evaluable MTAP-deletion patients, including ten (10) UC, nine (9)
adenocarcinoma NSCLC, and eight (8) squamous (sq) NSCLC patients at
the expansion dose of 30 mg QD of IDE397.
The clinical efficacy and tolerability data are preliminary and
based on investigator review from an unlocked database as of the
data analysis cutoff date of August
22, 2024.
The clinical data update in the twenty-seven (27) evaluable
patients by RECIST 1.1 include:
- ~33% Overall Response Rate (ORR). One (1) complete response (CR) and eight
(8) partial responses (PRs) by RECIST 1.1 evaluation out of
twenty-seven (27) evaluable patients. Nine (9) of nine (9)
responses have been confirmed by RECIST 1.1, including four (4) UC
patients, of which one was a CR, three (3) squamous NSCLC patients,
and two (2) adenocarcinoma NSCLC patients. Two patients confirmed
after the data cutoff date. In the earlier reported July 8, 2024, IDE397 webcast program update, five
(5) confirmed responses were reported out of eighteen (18)
evaluable patients. There were zero (0) non-evaluable patients
reported as of the data analysis.
- Confirmed ORR% by RECIST 1.1 by Solid Tumor Type: MTAP-deletion
UC = 40% (4 of 10) confirmed ORR%; MTAP-deletion squamous NSCLC =
~38% (3 of 8) confirmed ORR%; MTAP-deletion adenocarcinoma NSCLC =
~22% (2 of 9) confirmed ORR%
- Multiple confirmed partial responses by RECIST 1.1 harbor
genetic co-alterations, including MTAP-deletion and KRAS G12D
mutation in NSCLC, and MTAP-deletion and FGFR-TACC3 fusion in
UC
- ~93% Disease Control Rate (DCR). One (1) CR, eight (8) PRs, and
sixteen (16) stable disease (SD) by RECIST 1.1 evaluation out of
twenty-seven (27) evaluable patients
- Preliminary durability assessment: Fifteen (15) of twenty-seven
(27) patients still on treatment. Seven (7) of nine (9) RECIST 1.1
responses remain on treatment. Median duration of treatment (DOT)
has not been reached and is greater than 6.2 months and median time
to response (TTR) is ~2.7 months. The median duration of response
and median progression free survival data is still immature. Three
(3) UC patients on treatment greater than 250 days, four (4)
squamous NSCLC patients on treatment greater than 200 days, and
three (3) adenocarcinoma NSCLC patients on treatment greater than
200 days
- ~81% ctDNA Molecular Response Rate (MRR). Seventeen (17) of
twenty (21) patients with 50% or greater ctDNA reduction, and ~33%
(7 of 21) with deep 90% or greater ctDNA reduction. All MRs (17 of
17) were rapid occurring at the first ctDNA sample analysis. There
were several quality control failures of patient samples that led
to unavailability for MR analysis
- Favorable adverse event (AE) profile. Approximately 18% grade 3
or higher drug-related AEs and no drug-related serious adverse
events (SAEs) observed at the IDE397 30mg once-a-day expansion
dose. No drug-related AEs leading to discontinuations were
observed. We anticipate that the favorable AE profile and dosing
convenience of a 30 mg once-a-day tablet has the potential to
enable long-term dosing and combination development, including with
MTA-cooperative PRMT5 inhibitors and topoisomerase payload antibody
drug conjugates (ADCs)
ENA 2024 IDE397 and Trodelvy Clinical Combination Case Study
in MTAP-deletion UC
IDEAYA reports the first preliminary clinical case study of the
IDE397 and Trodelvy combination in MTAP-deletion UC, including a PR
by RECIST 1.1 in a patient case report with a genetic co-alteration
of MTAP-deletion and a FGFR3-TACC3 fusion, and rapid and deep
first-evaluation molecular responses with ctDNA reduction of
greater than 95% observed that will be presented at ENA 2024.
IDEAYA is targeting to initiate the IDE397 and Trodelvy Phase 1/2
combination expansion in MTAP-deletion UC in Q4 2024.
IDEAYA has activated over 35 clinical trial sites globally
in the U.S., Canada, Europe, and Asia
Pacific to enable potential rapid enrollment for the IDE397
Phase 2 monotherapy expansion in MTAP-deletion lung and bladder
cancer in its ongoing trial (NCT04794699). There is also an
ongoing Amgen-sponsored Phase 1/2 trial of the IDE397 and AMG 193
combination in MTAP-Deletion NSCLC (NCT05975073). IDEAYA published
at ENA 2024 preclinical combination efficacy data and the
combination mechanistic rationale for IDE397 with clinical stage
PRMT5 inhibitors, including BMS-986504 and AMG 193.
Next, IDEAYA is enrolling a Phase 1 clinical trial evaluating
the safety, tolerability, pharmacokinetics, pharmacodynamics and
efficacy of IDE397 in combination with Trodelvy in
MTAP-deletion UC patients (NCT04794699). Pursuant to the
clinical study collaboration and supply agreement, IDEAYA and
Gilead retain the commercial rights to their respective compounds,
including with respect to use as a monotherapy or combination
agent. IDEAYA is the study sponsor and Gilead will provide the
supply of Trodelvy to IDEAYA. IDE397 monotherapy or in combination
with Trodelvy has not been approved by any regulatory agency and
the efficacy and safety of this combination has not been
established.
36th edition of the EORTC-NCI-AACR Symposium (ENA
2024) in Barcelona,
Spain
Details of the late breaker oral presentation today are as
follows:
Presenter: Dr. Benjamin Herzberg, MD, Assistant
Professor, Columbia University
Title: Phase 1 expansion results of IDE397, a first-in-class,
oral, MAT2A inhibitor (MAT2Ai) in MTAP deleted(del) non-small cell
lung cancer (NSCLC) and urothelial cancer (UC)
Abstract #: 501 LBA
Session: Plenary Session 7, Late Breaking Abstracts and
Proffered Papers: Novel discoveries in drug development
Date and Time: Friday, October 25, 2024 at 3:54pm
CEST
In addition, IDEAYA had additional poster presentations at ENA
2024 highlighting preclinical data for the MAT2A and PARG programs.
In the ENA 2024 concomitant publication, IDE397 demonstrated deep
and durable regressions in combination with clinical stage PRMT5
inhibitors BMS-986504 and AMG 193 in multiple MTAP-deletion
preclinical models.
Poster presentation details are below:
Author: Garbett, D. et al.
Title: The mechanistic basis of both deep and durable
antitumor activity by combinatorial inhibition of MAT2A and PRMT5
in MTAP-deleted tumors
Poster Number: PB204
Session Title: Combination Therapies
Date and Time: Thursday, October 24, 2024, 9:00am - 5:30pm CEST, Exhibition Hall
Author: Munoz, D. et al.
Title: IDE161, a potential first-in-class clinical candidate
PARG inhibitor, selectively targets solid tumors with replication
stress and DNA repair vulnerabilities
Poster Number: PB337
Session Title: DNA Repair Modulation (e.g. PARP, CHK, ATR,
ATM)
Date and Time: Friday, October 25, 2024, 9:00am - 3:00pm CEST, Exhibition Hall
The IDE397 late breaker oral presentation at ENA 2024, as well
as an updated corporate presentation, which will incorporate the
IDE397 Phase 1 clinical data update from ENA 2024 at the 30mg RP2D
in UC and NSCLC patients, will be available on the company's
website, at its Investor Relations portal at approximately 10:15 am
ET on Friday, October 25, 2024, after
the presentation has concluded.
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 timing of enrollment for the IDE397 Phase 2
monotherapy expansion in MTAP-deletion lung and bladder cancer,
(iii) the timing of initiation of the IDE397 and Trodelvy Phase 1/2
combination expansion in MTAP-deletion UC and (iv) the timing
and content of future presentations. 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, 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 Annual Report on Form
10-K dated February 20, 2024 and any
current and periodic reports filed with the U.S. Securities and
Exchange Commission.
Investor and Media Contact
IDEAYA Biosciences
Andres Ruiz Briseno
SVP, Head of Finance and Investor Relations
investor@ideayabio.com
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