IDEAYA Announces Positive Interim Phase 1 Expansion Data of IDE397 in MTAP-Deletion Urothelial and Lung Cancer as Late-Breaker Oral Presentation at EORTC-NCI-AACR 2024
IDEAYA Biosciences announced positive Phase 1 expansion data for IDE397, a MAT2A inhibitor, in MTAP-deletion urothelial cancer (UC) and non-small cell lung cancer (NSCLC) patients. Key findings include a ~33% overall response rate with 1 complete response and 8 partial responses among 27 evaluable patients. The drug showed a 40% confirmed response rate in UC and ~38% in squamous NSCLC. The treatment demonstrated durability with median duration exceeding 6.2 months and a high disease control rate of 93%. Safety profile was favorable with no drug-related serious adverse events at the 30mg daily dose. The company plans to expand Phase 1/2 study combining IDE397 with Trodelvy® in MTAP-deletion UC in Q4 2024.
IDEAYA Biosciences ha annunciato dati positivi di espansione della Fase 1 per IDE397, un inibitore di MAT2A, nei pazienti con cancro uroteliale (UC) e cancro polmonare non a piccole cellule (NSCLC) con delezione di MTAP. I risultati chiave includono un tasso di risposta complessivo di circa il 33%, con 1 risposta completa e 8 risposte parziali tra 27 pazienti valutabili. Il farmaco ha mostrato un tasso di risposta confermato del 40% in UC e un tasso di circa il 38% in NSCLC squamoso. Il trattamento ha dimostrato una durata duratura con una durata mediana superiore a 6,2 mesi e un elevato tasso di controllo della malattia del 93%. Il profilo di sicurezza è stato favorevole, senza eventi avversi gravi correlati al farmaco alla dose giornaliera di 30 mg. L'azienda prevede di espandere lo studio di Fase 1/2 combinando IDE397 con Trodelvy® nell'UC con delezione di MTAP nel quarto trimestre del 2024.
IDEAYA Biosciences anunció datos positivos de expansión de la Fase 1 para IDE397, un inhibidor de MAT2A, en pacientes con cáncer urotelial (UC) y cáncer de pulmón no microcítico (NSCLC) con deleción de MTAP. Los hallazgos clave incluyen un tasa de respuesta global de aproximadamente el 33%, con 1 respuesta completa y 8 respuestas parciales entre 27 pacientes evaluables. El fármaco mostró un tasa de respuesta confirmada del 40% en UC y un tasa de aproximadamente el 38% en NSCLC escamoso. El tratamiento demostró durabilidad con una duración media superior a 6,2 meses y una alta tasa de control de la enfermedad del 93%. El perfil de seguridad fue favorable, sin eventos adversos graves relacionados con el fármaco a la dosis diaria de 30 mg. La empresa planea ampliar el estudio de Fase 1/2 combinando IDE397 con Trodelvy® en UC con deleción de MTAP en el cuarto trimestre de 2024.
IDEAYA 바이오사이언스가 MTAP 결실을 가진 요로상피암(UC)과 비소세포폐암(NSCLC) 환자의 IDE397에 대한 긍정적인 1상 확장 데이터를 발표했습니다. 주요 발견으로는 27명의 평가 가능한 환자 중 1명의 완전 반응과 8명의 부분 반응을 포함하여 약 33%의 전체 반응률이 있습니다. 이 약물은 UC에서 40%의 확인된 반응률을 보였고, 편평형 NSCLC에서 약 38%의 반응률을 보였습니다. 치료는 중간 지속 기간이 6.2개월을 초과하며 93%의 높은 질병 조절률을 보여주었습니다. 안전성 프로필은 좋았으며, 30mg의 일일 용량에서 약물 관련 중대한 부작용이 없었습니다. 이 회사는 2024년 4분기에 MTAP 결실 UC에 대해 IDE397과 Trodelvy®를 병합하는 1/2상 연구를 확대할 계획입니다.
IDEAYA Biosciences a annoncé des données positives d'expansion de la Phase 1 pour IDE397, un inhibiteur de MAT2A, chez des patients atteints de cancer urotélial (UC) et de cancer du poumon non à petites cellules (NSCLC) avec délétion de MTAP. Les résultats clés comprennent un taux de réponse global d'environ 33%, avec 1 réponse complète et 8 réponses partielles parmi 27 patients évaluable. Le médicament a montré un taux de réponse confirmé de 40% en UC et un taux d'environ 38% en NSCLC squameux. Le traitement a démontré une durabilité avec une durée médiane supérieure à 6,2 mois et un taux de contrôle de la maladie de 93%. Le profil de sécurité était favorable, sans événements indésirables graves liés au médicament à la dose quotidienne de 30 mg. L'entreprise prévoit d'élargir l'étude de Phase 1/2 combinant IDE397 avec Trodelvy® dans l'UC avec délétion de MTAP au quatrième trimestre 2024.
IDEAYA Biosciences hat positive Daten zur Phase 1-Expansion für IDE397, einen MAT2A-Inhibitor, bei Krebs des Urothels (UC) und nicht-kleinzelligem Lungenkrebs (NSCLC) mit MTAP-Deletion veröffentlicht. Zu den wichtigsten Ergebnissen gehört eine gesamte Ansprechrate von etwa 33% mit 1 vollständiger Antwort und 8 teilweisen Antworten bei 27 auswertbaren Patienten. Das Medikament zeigte eine bestätigte Ansprechrate von 40% bei UC und etwa 38% bei plattenepithelialem NSCLC. Die Behandlung zeigte eine Haltbarkeit mit einer medianen Dauer von über 6,2 Monaten und einer hohen Krankheitskontrollrate von 93%. Das Sicherheitsprofil war günstig, ohne schwere nebenwirkungsbedingte Ereignisse bei einer Tagesdosis von 30 mg. Das Unternehmen plant, die Phase 1/2-Studie, die IDE397 mit Trodelvy® bei MTAP-Deletion UC kombiniert, im vierten Quartal 2024 auszubauen.
- 33% overall response rate with 9 confirmed responses out of 27 patients
- 40% confirmed response rate in urothelial cancer patients
- 93% disease control rate across all patients
- 81% molecular response rate with 17 of 21 patients showing ctDNA reduction
- Favorable safety profile with no drug-related serious adverse events
- Median duration of treatment exceeding 6.2 months
- Median duration of response and progression free survival data still immature
- Lower response rate in adenocarcinoma NSCLC (22%) compared to other cancer types
Insights
The Phase 1 expansion data for IDE397 shows remarkable clinical efficacy in treating MTAP-deletion cancers, with a
The drug's safety profile is notably favorable, with only
This data represents a significant market opportunity, targeting an estimated 48,000 annual MTAP-deletion patients in the U.S. across urothelial cancer and NSCLC alone. With no FDA-approved therapies specifically for MTAP-deletion tumors, IDE397 could capture substantial market share as a first-in-class treatment. The expansion potential into additional cancer types like pancreatic (
- ~
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 of93% (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
"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
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 with50% or greater ctDNA reduction, and ~33% (7 of 21) with deep90% 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
IDEAYA has activated over 35 clinical trial sites globally in the
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
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
Investor and Media Contact
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