Relay Therapeutics Announces Updated Interim Data for RLY-2608 + Fulvestrant Demonstrating Continued Maturation of Clinically Meaningful Progression Free Survival
Relay Therapeutics (RLAY) announced updated interim data for RLY-2608, showing an 11.4-month median progression-free survival in second-line patients with PI3Kα-mutated, HR+/HER2- metastatic breast cancer at the recommended Phase 2 dose. The study demonstrated a 39% confirmed objective response rate across all patients and 67% in patients with kinase mutations.
The drug showed a favorable tolerability profile, with 94% median dose intensity and mostly low-grade treatment-related adverse events. Among 64 patients at the recommended dose, only 31% experienced Grade 3 adverse events, with no Grade 4-5 events reported.
The company plans to initiate a pivotal Phase 2 study in 2025 and reported approximately $840 million in cash and investments as of Q3 2024.
Relay Therapeutics (RLAY) ha annunciato dati interim aggiornati per RLY-2608, mostrando una mediana di sopravvivenza libera da progressione di 11,4 mesi nei pazienti di seconda linea con carcinoma mammario metastatico PI3Kα-mutato, HR+/HER2-. Lo studio ha evidenziato un tasso di risposta obiettiva confermato del 39% in tutti i pazienti e 67% nei pazienti con mutazioni chinasi.
Il farmaco ha mostrato un profilo di tollerabilità favorevole, con una intensità di dose mediana del 94% e prevalentemente eventi avversi di bassa gradazione legati al trattamento. Tra 64 pazienti alla dose raccomandata, solo il 31% ha sperimentato eventi avversi di Grado 3, senza eventi di Grado 4-5 riportati.
L'azienda prevede di avviare uno studio cruciale di Fase 2 nel 2025 e ha riportato circa 840 milioni di dollari in liquidità e investimenti al Q3 2024.
Relay Therapeutics (RLAY) anunció datos intermedios actualizados para RLY-2608, mostrando una supervivencia libre de progresión mediana de 11.4 meses en pacientes de segunda línea con cáncer de mama metastásico HR+/HER2- mutado por PI3Kα. El estudio demostró una tasa de respuesta objetiva confirmada del 39% entre todos los pacientes y 67% en pacientes con mutaciones de quinasa.
El fármaco mostró un perfil de tolerabilidad favorable, con una intensidad de dosis mediana del 94% y en su mayoría eventos adversos relacionados con el tratamiento de bajo grado. Entre 64 pacientes a la dosis recomendada, solo el 31% experimentó eventos adversos de Grado 3, sin eventos de Grado 4-5 reportados.
La compañía planea iniciar un estudio pivotal de Fase 2 en 2025 y reportó aproximadamente 840 millones de dólares en efectivo e inversiones a partir del Q3 2024.
릴레이 테라퓨틱스 (RLAY)는 RLY-2608의 업데이트된 중간 데이터를 발표하며, PI3Kα 변이가 있는 HR+/HER2- 전이성 유방암을 가진 2차 환자에서 11.4개월의 중앙 무진행 생존 기간을 보였다고 밝혔습니다. 이 연구는 모든 환자에서 39%의 확정된 객관적 반응률과 키나제 변이가 있는 환자에서 67%을 나타냈습니다.
이 약물은 94% 중앙 용량 강도와 대부분 저급도의 치료 관련 부작용으로 유리한 내약성 프로필을 보였습니다. 추천 용량의 64명 환자 중 31%만이 3등급 부작용을 경험했으며, 4-5등급 부작용은 보고되지 않았습니다.
회사는 2025년에 결정적 2상 연구를 시작할 계획이며, 2024년 3분기 기준으로 약 8억 4천만 달러의 현금 및 투자를 보고했습니다.
Relay Therapeutics (RLAY) a annoncé des données intérimaires mises à jour pour RLY-2608, montrant une durée médiane de survie sans progression de 11,4 mois chez des patients de deuxième ligne atteints d'un cancer du sein métastatique HR+/HER2- muté par PI3Kα à la dose recommandée de phase 2. L'étude a démontré un taux de réponse objective confirmé de 39% chez tous les patients et 67% chez les patients présentant des mutations de kinases.
Le médicament a montré un profil de tolérance favorable, avec une intensité médiane de dose de 94% et des événements indésirables liés au traitement principalement de faible gravité. Parmi 64 patients recevant la dose recommandée, seulement 31% ont éprouvé des événements indésirables de grade 3, sans aucun événement de grade 4-5 rapporté.
L'entreprise prévoit d'initier une étude pivot de phase 2 en 2025 et a rapporté environ 840 millions de dollars en liquidités et investissements au troisième trimestre 2024.
Relay Therapeutics (RLAY) hat aktualisierte Zwischenwerte für RLY-2608 bekannt gegeben und zeigt eine medianen Progressionsfreie Überlebenszeit von 11,4 Monaten bei Patienten in der zweiten Linie mit PI3Kα-mutiertem, HR+/HER2- metastasiertem Brustkrebs in der empfohlenen Dosierung der Phase 2. Die Studie zeigte eine bestätigte objektive Ansprechrate von 39% bei allen Patienten und 67% bei Patienten mit Kinase-Mutationen.
Das Medikament zeigte ein günstiges Verträglichkeitsprofil mit 94% medianer Dosisintensität und größtenteils milden behandlungsbedingten Nebenwirkungen. Von 64 Patienten bei der empfohlenen Dosis hatten nur 31% Nebenwirkungen der Grad 3, ohne berichtete Nebenwirkungen der Grade 4-5.
Das Unternehmen plant, 2025 eine entscheidende Phase-2-Studie zu initiieren und berichtete bis zum dritten Quartal 2024 über etwa 840 Millionen Dollar an Bargeld und Investitionen.
- 11.4-month median PFS in 2L patients, more than twice existing standards-of-care
- 67% confirmed ORR in patients with kinase mutations at RP2D
- 94% median dose intensity indicating strong tolerability
- Strong cash position of $840M to support pivotal trial completion
- 74% of patients experienced tumor reductions
- Only 39% confirmed ORR across all patients
- 31% of patients experienced Grade 3 treatment-related adverse events
- Two patients discontinued treatment due to adverse events
Insights
New interim data show 11.4-month median PFS in 2L patients with PI3Kα-mutated, HR+/HER2- metastatic breast cancer at RP2D
Data support planned initiation of 2L pivotal study in 2025
Next-generation triplet combination with atirmociclib (CDK4-selective) initiated & ribociclib triplet combination ongoing
Relay Therapeutics to host a conference call today, December 11, at 7am ET (6am CT)
SAN ANTONIO, Dec. 11, 2024 (GLOBE NEWSWIRE) -- Relay Therapeutics, Inc. (Nasdaq: RLAY), a clinical-stage precision medicine company transforming the drug discovery process by combining leading-edge computational and experimental technologies, today announced updated interim clinical data for RLY-2608, the first known investigational allosteric, pan-mutant and isoform-selective inhibitor of PI3Kα. The updated data show a median progression free survival (PFS) of 11.4 months in second line (2L) patients with PI3Kα-mutated, HR+, HER2- locally advanced or metastatic breast cancer who received RLY-2608 600mg twice daily (BID) + fulvestrant. These data are being presented today at the San Antonio Breast Cancer Symposium (SABCS) 2024.
“These updated data help build on previously reported results that show a level of benefit that had not previously been seen with non-selective PI3Kα inhibitors,” said Don Bergstrom, M.D., Ph.D., President of R&D at Relay Therapeutics. “We are particularly encouraged to see even greater benefit observed in the patients in which we are working to start a pivotal study next year; in these 2L patients, RLY-2608 + fulvestrant demonstrated a median progression free survival that is more than twice that of the existing standards-of-care.”
ReDiscover – RLY-2608 First-in-Human Study
RLY-2608 is currently being evaluated in ReDiscover, an ongoing first-in-human study, which was designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary antitumor activity of RLY-2608 in combination with fulvestrant, and in combination with fulvestrant and ribociclib or atirmociclib (Pfizer’s selective CDK4 inhibitor).
The RLY-2608 + fulvestrant arm of the study, as of the November 4, 2024 interim data cut-off for this arm, had enrolled 118 patients with PI3Kα-mutated, HR+, HER2- locally advanced or metastatic breast cancer across all doses in both the dose escalation and dose expansion portions of the study, including 64 patients at the company’s recommended Phase 2 dose (RP2D) of 600mg BID. Among these 64 patients, 31 had a kinase mutation and 33 had a non-kinase mutation. Twelve patients also had a PTEN or AKT co-mutation and were therefore excluded from the efficacy analysis, consistent with the planned pivotal population.
The RLY-2608 + ribociclib + fulvestrant arm of the study continues to enroll patients with PI3Kα-mutated, HR+, HER2- locally advanced or metastatic breast cancer in dose escalation. The RLY-2608 + atirmociclib + fulvestrant arm of the study has recently been initiated.
Patients were Heavily Pre-Treated
All RLY-2608 + fulvestrant patients across doses had received a significant level of prior therapy in the advanced setting, including at least one prior endocrine therapy and at least one prior CDK4/6 inhibitor. Among the 64 patients who received the RP2D:
41% of patients (n=26) had received two or more prior lines of therapy52% of patients (n=33) had received a prior selective estrogen-receptor degrader (SERD), such as fulvestrant or a novel SERD25% of patients (n=16) had received chemotherapy or an ADC59% of patients (n=38) had visceral metastases34% of patients (n=22) had a BMI of at least 30 and/or HbA1c of at least5.7%
Promising Efficacy Data in Proposed Pivotal Population
Among the 52 RLY-2608 + fulvestrant patients who received the RP2D and did not have a PTEN or AKT co-mutation:
- The median PFS was 9.2 months for all patients and 11.4 months for 2L patients
- Median PFS was 11.4 months for patients with kinase mutations
- Clinical benefit rate (CBR) was
67% across all patients (32 of 48 CBR-evaluable patients; CBR defined as the proportion of patients with complete response, partial response or stable disease for at least 24 weeks) - Among the 31 patients with measurable disease, 12 achieved a partial response (PR) (
39% confirmed objective response rate, ORR)- Nearly three quarters of patients experienced tumor reductions (
74% ; n=23)
- Nearly three quarters of patients experienced tumor reductions (
- Among the 15 patients with measurable disease who had a kinase mutation, two thirds achieved a PR (
67% confirmed ORR; n=10) - Median follow-up was 9.5 months
Maintained Meaningfully Differentiated Tolerability Profile
RLY-2608 + fulvestrant was generally well tolerated in the 118 patients treated across all doses as of the data cut-off date. The overall tolerability profile consisted of mostly low-grade treatment-related adverse events (TRAEs) that were manageable and reversible. Safety outcomes were generally as expected across dose levels based on exposure and consistent with mutant-selective PI3Kα inhibition. Among the 64 patients who received the RP2D:
- The low rate of TRAE-related dose modifications allowed for
94% median dose intensity - Only two patients discontinued treatment due to TRAEs (Grade 1 pruritis; Grade 1 nausea, loss of appetite)
- The majority of hyperglycemia was Grade 1; only two patients (
3% ) experienced Grade 3 hyperglycemia; no Grade 4-5 hyperglycemia - Only
31% of patients experienced a Grade 3 TRAE; no Grade 4-5 TRAEs
Continued Progression of Front-Line Breast Cancer Regimens
Two front-line triplet regimens are being progressed – one with the existing CDK4/6 standard-of-care ribociclib and one with Pfizer’s investigative selective-CDK4 inhibitor atirmociclib. RLY-2608 + ribociclib + fulvestrant dose escalation is ongoing with biologically active doses of RLY-2608. The RLY-2608 + atirmociclib + fulvestrant arm of the ReDiscover study has been initiated.
Anticipated RLY-2608 Next Steps
- Breast Cancer:
- Initiate 2L pivotal study of RLY-2608 + fulvestrant in 2025
- Disclose complete Phase 1/2 data in 2025
- Vascular Malformations:
- Initiate vascular malformations study in the first quarter of 2025
- Initiate vascular malformations study in the first quarter of 2025
Cash balance will be operationalized to preserve ability to complete 2L pivotal study
As of the end of the third quarter of 2024, cash, cash equivalents and investments were approximately
Conference Call Information
Relay Therapeutics will host a conference call and live webcast today, December 11, 2024, at 7:00 a.m. ET (6:00 a.m. CT). Registration and dial-in for the conference call may be accessed through Relay Therapeutics’ website under Events in the News & Events section through the following link: https://ir.relaytx.com/news-events/events-presentations. An archived replay of the webcast will be available following the event.
The data presentation from the San Antonio Breast Cancer Symposium is also available on the Relay Therapeutics website in the “Publications/Presentations” section through the following link: https://relaytx.com/pipeline/.
About RLY-2608
RLY-2608 is the lead program in Relay Therapeutics’ efforts to discover and develop mutant selective inhibitors of PI3Kα, the most frequently mutated kinase in all cancers, with oncogenic mutations detected in about
Traditionally, the development of PI3Kα inhibitors has focused on the active, or orthosteric, site. The therapeutic index of orthosteric inhibitors is limited by the lack of clinically meaningful selectivity for mutant versus wild-type (WT) PI3Kα and off-isoform activity. Toxicity related to inhibition of WT PI3Kα and other PI3K isoforms results in sub-optimal inhibition of mutant PI3Kα with reductions in dose intensity and frequent discontinuation. The Dynamo® platform enabled the discovery of RLY-2608, the first known allosteric, pan-mutant, and isoform-selective PI3Kα inhibitor, designed to overcome these limitations. Relay Therapeutics solved the full-length cryo-EM structure of PI3Kα, performed computational long time-scale molecular dynamic simulations to elucidate conformational differences between WT and mutant PI3Kα, and leveraged these insights to support the design of RLY-2608. RLY-2608 is currently being evaluated in a first-in-human study designed to treat patients with advanced solid tumors with a PIK3CA (PI3Kα) mutation. For more information on RLY-2608, please visit here.
About Relay Therapeutics
Relay Therapeutics is a clinical-stage precision medicine company transforming the drug discovery process by combining leading-edge computational and experimental technologies with the goal of bringing life-changing therapies to patients. As the first of a new breed of biotech created at the intersection of complementary techniques and technologies, Relay Therapeutics aims to push the boundaries of what’s possible in drug discovery. Its Dynamo® platform integrates an array of leading-edge computational and experimental approaches designed to drug protein targets that have previously been intractable or inadequately addressed. Relay Therapeutics’ initial focus is on enhancing small molecule therapeutic discovery in targeted oncology and genetic disease indications. For more information, please visit www.relaytx.com or follow us on Twitter.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, implied and express statements regarding Relay Therapeutics’ strategy, business plans and focus; the progress and timing of the clinical development of the programs across Relay Therapeutics’ portfolio; the expected therapeutic benefits and potential efficacy and tolerability of RLY-2608, both as a monotherapy and in combination with other agents, and its other programs, as well as the clinical data for RLY-2608; the interactions with regulatory authorities and any related approvals; the potential market opportunity for RLY-2608; the cash runway projection and the expectations regarding Relay Therapeutics’ use of capital and expenses. The words “may,” “might,” “will,” “could,” “would,” “should,” “plan,” “anticipate,” “intend,” “believe,” “expect,” “estimate,” “seek,” “predict,” “future,” “project,” “potential,” “continue,” “target” and similar words or expressions, or the negative thereof, are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words.
Any forward-looking statements in this press release are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, risks associated with: the impact of global economic uncertainty, geopolitical instability and conflicts, or public health epidemics or outbreaks of an infectious disease on countries or regions in which Relay Therapeutics has operations or does business, as well as on the timing and anticipated results of its clinical trials, strategy, future operations and profitability; the delay or pause of any current or planned clinical trials or the development of Relay Therapeutics’ drug candidates; the risk that the preliminary or interim results of its preclinical or clinical trials may not be predictive of future or final results in connection with future clinical trials of its product candidates and that interim and early clinical data may change as more patient data become available and are subject to audit and verification procedures; Relay Therapeutics’ ability to successfully demonstrate the safety and efficacy of its drug candidates; the timing and outcome of its planned interactions with regulatory authorities; and obtaining, maintaining and protecting its intellectual property. These and other risks and uncertainties are described in greater detail in the section entitled “Risk Factors” in Relay Therapeutics’ most recent Annual Report on Form 10-K and Quarterly Report on Form 10-Q, as well as any subsequent filings with the Securities and Exchange Commission. In addition, any forward-looking statements represent Relay Therapeutics' views only as of today and should not be relied upon as representing its views as of any subsequent date. Relay Therapeutics explicitly disclaims any obligation to update any forward-looking statements. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements.
Contact:
Megan Goulart
617-322-0814
mgoulart@relaytx.com
Media:
Dan Budwick
1AB
973-271-6085
dan@1abmedia.com
FAQ
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