Erasca Initiates SEACRAFT-2 Pivotal Phase 3 Trial Evaluating Naporafenib Plus Trametinib in Patients With NRAS-Mutant Melanoma
Erasca Initiates SEACRAFT-2 Pivotal Phase 3 Trial Evaluating Naporafenib Plus Trametinib in Patients With NRAS-Mutant Melanoma
Naporafenib is a potential first-in-class and best-in-class pan-RAF inhibitor for multiple RAS/MAPK pathway-driven tumors and has been dosed in over 500 patients to date
Naporafenib是潛在的同類首創和同類最佳的泛RAF抑制劑，用於治療多種RAS/MAPK路徑驅動的腫瘤，迄今已在500多名患者中服用
Favorable mOS and mPFS demonstrated in pooled analysis of Phase 1b and Phase 2 trials in NRASm melanoma
nRasm 黑色素瘤的 1b 期和 2 期試驗的合併分析顯示出有利的 MoS 和 MPF
Randomized Stage 1 readout for naporafenib plus trametinib vs. trametinib monotherapy expected in 2025
納波拉非尼加曲美替尼與曲美替尼單一療法的隨機第一階段讀數預計將在2025年公佈
SAN DIEGO, June 18, 2024 (GLOBE NEWSWIRE) -- Erasca, Inc. (Nasdaq: ERAS), a clinical-stage precision oncology company singularly focused on discovering, developing, and commercializing therapies for patients with RAS/MAPK pathway-driven cancers, today announced the initiation of the global SEACRAFT-2 Phase 3 trial evaluating the pan-RAF inhibitor naporafenib in combination with the MEK inhibitor trametinib (MEKINIST) in patients with NRAS-mutant (NRASm) melanoma. Naporafenib is a potential first-in-class and best-in-class pan-RAF inhibitor that has been dosed in over 500 patients to date and is being developed to treat multiple types of RAS/MAPK pathway-driven tumors.
聖地亞哥，2024年6月18日（GLOBE NEWSWIRE）——Erasca, Inc.（納斯達克股票代碼：ERAS）是一家臨床階段的精準腫瘤學公司，專門致力於發現、開發和商業化針對RAS/MAPK路徑驅動的癌症患者的療法，今天宣佈啓動全球癌症療法 SEACRAFT-2 評估泛RAF抑制劑納波拉非尼與MEK抑制劑曲美替尼（MEKINIST）聯合治療NRAS突變體（NRASM）黑色素瘤患者的3期試驗。Naporafenib是一種潛在的同類首創和同類最佳的泛RAF抑制劑，迄今已在500多名患者中服用，並且正在開發用於治療多種類型的RAS/MAPK路徑驅動的腫瘤。
"NRASm melanoma is an aggressive disease with no approved targeted therapies, underscoring the high unmet need for these patients. We are pleased to announce the initiation of our SEACRAFT-2 pivotal Phase 3 trial, which has a two-stage design. Importantly, Stage 1 is expected to provide a randomized data readout of naporafenib plus trametinib against single agent trametinib in 2025 and will inform the randomized Phase 2 dose (RP2D) for the combination," said Shannon R. Morris, M.D., Ph.D., Erasca's chief medical officer. "Stage 2, which incorporates feedback from the United States Food and Drug Administration (FDA) and European health authorities, is designed for regulatory approval and will compare the combination against physician's choice of chemotherapy or a single agent MEK inhibitor using dual primary endpoints of progression free survival (PFS) and overall survival (OS)."
“nRasm 黑色素瘤是一種侵襲性疾病，沒有獲得批准的靶向療法，這凸顯了這些患者大量未得到滿足的需求。我們很高興地宣佈，我們的 SEACRAFT-2 關鍵性三期試驗已啓動，該試驗採用兩階段設計。重要的是，第一階段預計將在2025年提供納波拉非尼加曲美替尼對比單劑曲美替尼的隨機數據讀數，並將爲該組合的隨機2期劑量（RP2D）提供信息。” 埃拉斯卡首席醫學官香農·莫里斯醫學博士（Shannon R. Morris）博士說。“第二階段納入了美國食品藥品監督管理局（FDA）和歐洲衛生當局的反饋，旨在獲得監管部門的批准，並將使用無進展生存期（PFS）和總生存期（OS）這兩個主要終點將該組合與醫生選擇的化療或單藥MEK抑制劑進行比較。”
A pooled analysis of the Phase 1b and Phase 2 trials of patients with NRASm melanoma dosed with naporafenib in combination with trametinib showed a median OS (mOS) of 13.0 and 14.1 months and a median PFS (mPFS) of 5.1 and 4.9 months at two doses of the combination, respectively. The pooled dataset at each dose compares favorably relative to historical benchmarks.
對給藥納波非尼與曲美替尼的nRasm黑色素瘤患者的1b期和2期試驗的合併分析顯示，兩劑組合的中位操作系統（MoS）爲13.0和14.1個月，中位PFS（MPF）分別爲5.1和4.9個月。與歷史基準相比，每劑量的合併數據集都處於有利地位。
About SEACRAFT-2
SEACRAFT-2 is a randomized, pivotal Phase 3 trial evaluating the clinical efficacy of naporafenib in combination with trametinib (MEKINIST) compared to physician's choice of therapy (dacarbazine, temozolomide, or trametinib monotherapy) in the post-immunotherapy setting in patients with NRAS-mutant metastatic melanoma. A randomized Stage 1 readout for naporafenib plus trametinib compared to trametinib alone is expected in 2025.
關於 SEACRAFT-2
SEACRAFT-2 是一項隨機的關鍵性三期試驗，評估了納波非尼聯合曲美替尼（MEKINIST）與醫生選擇的療法（達卡巴嗪、替莫唑胺或曲美替尼單一療法）在免疫後治療環境中對NRAS突變轉移性黑色素瘤患者選擇的療法（達卡巴嗪、替莫唑胺或曲美替尼單一療法）的臨床療效。與單獨使用曲美替尼相比，納波拉非尼加曲美替尼的隨機第一階段讀數預計將在2025年公佈。
About Naporafenib
Naporafenib (formerly LXH254) is a potent and selective pan-RAF inhibitor, with a potential first-in-class and best-in-class profile. Naporafenib has been dosed in over 500 patients to date, whereby safety, tolerability, pharmacokinetics, and pharmacodynamics have been established in both monotherapy and select combinations. Clinical proof-of-concept (PoC) has been established for the combination with trametinib for patients with NRAS-mutant (NRASm) melanoma, which includes NRAS Q61X melanoma, and preliminary clinical PoC has been established for the combination with trametinib for patients with RAS Q61X in non-small cell lung cancer (NSCLC). Erasca plans to focus initially on advancing and securing regulatory approval for naporafenib plus trametinib in NRASm melanoma as part of the SEACRAFT-2 pivotal Phase 3 trial and in RAS Q61X solid tumors as part of the ongoing SEACRAFT-1 Phase 1b trial, respectively. Erasca is also exploring additional combinations of naporafenib with other proprietary therapeutic agents in our pipeline. Naporafenib has received Fast Track Designation from the United States Food and Drug Administration (FDA) for patients with advanced NRASm melanoma.
關於納波拉非尼
Naporafenib（前身爲 LXH254）是一種有效的選擇性泛RAF抑制劑，可能具有同類首創和同類最佳的特點。迄今爲止，Naporafenib已在500多名患者中服用，從而在單一療法和精選組合中都確立了安全性、耐受性、藥代動力學和藥效學。與曲美替尼聯合治療包括NRAS Q61X黑色素瘤的NRAS突變體（nRASM）黑色素瘤患者的臨床概念驗證（PoC）已經確定，對於非小細胞肺癌（NSCLC）RAS Q61X患者，與曲美替尼聯合使用的初步臨床PoC已經建立。作爲 SEACRAFT-2 關鍵性三期試驗的一部分，埃拉斯卡計劃最初專注於推進和確保納波非尼加曲美替尼用於治療nRasm黑色素瘤的監管批准，作爲正在進行的 SEACRAFT-1 1b期試驗的一部分，在RAS Q61X實體瘤中分別獲得監管部門的批准。埃拉斯卡還在探索納波非尼與其他專有治療藥物的更多組合。Naporafenib已獲得美國食品藥品監督管理局（FDA）頒發的針對晚期nRasm黑色素瘤患者的快速通道認證。
About Erasca
At Erasca, our name is our mission: To erase cancer. We are a clinical-stage precision oncology company singularly focused on discovering, developing, and commercializing therapies for patients with RAS/MAPK pathway-driven cancers. Our company was co-founded by leading pioneers in precision oncology and RAS targeting to create novel therapies and combination regimens designed to comprehensively shut down the RAS/MAPK pathway for the treatment of cancer. We have assembled one of the deepest RAS/MAPK pathway-focused pipeline in the industry. We believe our team's capabilities and experience, further guided by our scientific advisory board which includes the world's leading experts in the RAS/MAPK pathway, uniquely position us to achieve our bold mission of erasing cancer.
關於 Erasca
在埃拉斯卡，我們的名字就是我們的使命：消滅癌症。我們是一家臨床階段的精準腫瘤學公司，專注於爲RAS/MAPK路徑驅動的癌症患者發現、開發和商業化療法。我們公司由精準腫瘤學和RAS領域的領先先驅共同創立，旨在開發旨在全面關閉癌症治療RAS/MAPK途徑的新療法和聯合方案。我們已經組裝了業內最深的以RAS/MAPK路徑爲重點的管道之一。我們相信，在包括RAS/MAPK途徑領域的世界領先專家在內的科學顧問委員會的進一步指導下，我們團隊的能力和經驗，使我們能夠獨特地實現消滅癌症的大膽使命。
Cautionary Note Regarding Forward-Looking Statements
Erasca cautions you that statements contained in this press release regarding matters that are not historical facts are forward-looking statements. The forward-looking statements are based on our current beliefs and expectations and include, but are not limited to: our expectations regarding the potential therapeutic benefits of our product candidates, including naporafenib; the planned advancement of our development pipeline, including the anticipated timing of the Stage 1 data readout for the SEACRAFT-2 trial, and other upcoming development milestones. Actual results may differ from those set forth in this press release due to the risks and uncertainties inherent in our business, including, without limitation: our approach to the discovery and development of product candidates based on our singular focus on shutting down the RAS/MAPK pathway, a novel and unproven approach; the analysis of pooled Phase 1 and Phase 2 naporafenib plus trametinib data covers two clinical trials with different designs and inclusion criteria, which cannot be directly compared, and therefore may not be a reliable indicator of mOS data; due to differences between trial designs and subject characteristics, comparing data across different trials may not be a reliable indicator of data; results from preclinical studies or early clinical trials, including the clinical trial results discussed in this press release, not necessarily being predictive of future results; unfavorable results from preclinical studies or clinical trials; we have not completed any clinical trials of naporafenib and are reliant on data generated by Novartis in prior clinical trials conducted by it; our planned SEACRAFT trials may not support the registration of naporafenib; later developments with the FDA or EU health authorities may be inconsistent with the feedback received to date regarding our development plans and trial designs; our assumptions around which programs may have a higher probability of success may not be accurate, and we may expend our limited resources to pursue a particular product candidate and/or indication and fail to capitalize on product candidates or indications with greater development or commercial potential; potential delays in the commencement, enrollment, and completion of clinical trials and preclinical studies; our dependence on third parties in connection with manufacturing, research, and preclinical and clinical testing; unexpected adverse side effects or inadequate efficacy of our product candidates that may limit their development, regulatory approval, and/or commercialization, or may result in recalls or product liability claims; the inability to realize any benefits from our current licenses, collaborations, acquisitions, and collaborations, and any future licenses, acquisitions, or collaborations, and our ability to fulfill our obligations under such arrangements; our ability to obtain and maintain intellectual property protection for our product candidates; regulatory developments in the United States and foreign countries; Fast Track Designation may not lead to a faster development or regulatory review or approval process, and does not increase the likelihood that our product candidates will receive marketing approval; our ability to fund our operating plans with our current cash, cash equivalents, and marketable securities; and other risks described in our prior filings with the Securities and Exchange Commission (SEC), including under the heading "Risk Factors" in our annual report on Form 10-K for the year ended December 31, 2023, and any subsequent filings with the SEC. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and we undertake no obligation to update such statements to reflect events that occur or circumstances that exist after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995.
關於前瞻性陳述的警示說明
埃拉斯卡提醒您，本新聞稿中有關非歷史事實事項的陳述均爲前瞻性陳述。前瞻性陳述基於我們當前的信念和預期，包括但不限於：我們對包括納波非尼在內的候選產品的潛在治療益處的預期；我們開發渠道的計劃進展，包括 SEACRAFT-2 試驗第一階段數據讀取的預期時間以及其他即將到來的開發里程碑。由於我們業務固有的風險和不確定性，實際結果可能與本新聞稿中列出的結果有所不同，包括但不限於：我們發現和開發候選產品的方法以關閉RAS/MAPK途徑爲唯一重點，這是一種未經證實的新方法；對1期和2期納波拉非尼加曲美替尼合併數據的分析涵蓋了兩項具有不同設計和納入標準的臨床試驗，其中無法直接比較，因此可能不是 MoS 數據的可靠指標；由於試驗設計和受試者特徵之間的差異，比較不同試驗的數據可能不是可靠的數據指標；臨床前研究或早期臨床試驗的結果，包括本新聞稿中討論的臨床試驗結果，不一定能預測未來的結果；臨床前研究或臨床試驗的不利結果；我們尚未完成納波拉非尼的任何臨床試驗，依賴諾華在先前進行的臨床試驗中生成的數據；我們計劃的 SEACRAFT 試驗可能不支持納泊非尼的註冊；美國食品和藥物管理局或歐盟衛生當局的後續進展可能與迄今爲止收到的有關我們的開發計劃和試驗設計的反饋不一致；我們對哪些項目可能更有可能成功的假設可能不準確，我們可能會花費有限的資源來尋找特定的候選產品和/或適應症，而未能利用具有更大開發或商業潛力的候選產品或適應症；啓動和註冊可能出現延遲，以及臨床試驗和臨床前研究的完成；我們在製造、研究、臨床前和臨床測試方面對第三方的依賴；我們的候選產品出現意想不到的不良副作用或療效不足，可能會限制其開發、監管批准和/或商業化，或可能導致召回或產品責任索賠；無法從我們當前的許可、合作、收購和合作以及未來的任何許可、收購或合作中獲得任何好處，以及我們的履行此類安排下的義務的能力；我們爲候選產品獲得和維持知識產權保護的能力；美國和國外的監管發展；快速通道指定可能不會加快開發或監管審查或批准程序，也不會增加我們的候選產品獲得上市批准的可能性；我們用當前的現金、現金等價物和有價證券爲運營計劃提供資金的能力；以及我們之前描述的其他風險向美國證券交易委員會（SEC）提交的文件，包括我們在截至2023年12月31日的10-K表年度報告中在 “風險因素” 標題下提交的文件，以及隨後向美國證券交易委員會提交的任何文件。提醒您不要過分依賴這些前瞻性陳述，這些陳述僅代表截至本文發佈之日，我們沒有義務更新此類陳述以反映在本聲明發布之日之後發生的事件或存在的情況。本警示聲明是根據1995年《私人證券訴訟改革法》的安全港條款作出的，對所有前瞻性陳述進行了全面的限定。
MEKINIST is a registered trademark owned by or licensed to Novartis AG, its subsidiaries, or affiliates.
MEKINIST 是諾華股份公司、其子公司或關聯公司擁有或許可的註冊商標。
Contact:
Joyce Allaire
LifeSci Advisors, LLC
jallaire@lifesciadvisors.com
聯繫人：
喬伊斯·阿萊爾
LifeSci 顧問有限公司
jallaire@lifesciadvisors.com
Source: Erasca, Inc.
資料來源：Erasca, Inc.
Source: Erasca, Inc.
資料來源：Erasca, Inc.
譯文內容由第三人軟體翻譯。