Erasca Announces First Patient Dosed in HERKULES-1 Phase 1b Trial Evaluating ERAS-007 and ERAS-601 MAPKlamp Combination in RAS/MAPK Pathway-Altered Solid Tumors
Promising preliminary monotherapy data for ERK1/2 inhibitor ERAS-007 and SHP2 inhibitor ERAS-601 in advanced solid tumors, which had favorable safety, tolerability, and efficacy profiles that support combination development
BRAF Class 2 and 3 alterations have no approved targeted therapies and represent up to 25% of all BRAF-driven tumors
SAN DIEGO, Dec. 20, 2022 (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 dosing of the first patient in the HERKULES-1 Phase 1b trial evaluating ERK1/2 inhibitor ERAS-007 in combination with SHP2 inhibitor ERAS-601 (together, Erasca’s first MAPKlamp) in patients with RAS/MAPK pathway-altered solid tumors.
“We are pleased with our team’s efficient execution that resulted in dosing the first patient in our MAPKlamp trial in 2022 ahead of schedule,” said Jonathan E. Lim, M.D., Erasca’s chairman, CEO, and co-founder. “ERK and SHP2 inhibition with ERAS-007 and ERAS-601 targets critical downstream and upstream nodes in the RAS/MAPK pathway, offering a rational approach that is supported by early clinical data that we presented at our R&D Day in September. Notably, we reported four responses in nine patients with BRAF-driven tumors to either monotherapy ERAS-007 or ERAS-601. Three of these responses were in tumors with BRAF Class 2 or 3 alterations, including a confirmed response to monotherapy SHP2 inhibition in a patient with a BRAF Class 3 alteration, which is dependent on upstream receptor tyrosine kinase (RTK) activation. We look forward to exploring the potential to address the high unmet need in these BRAF subtypes, which have no approved targeted therapies and represent up to 25% of all BRAF-driven tumors.”
The MAPKlamp portion of HERKULES-1 will initially examine the safety, tolerability, and preliminary efficacy of ERAS-007 in combination with ERAS-601 in patients with RAS/MAPK pathway-altered solid tumors. After a recommended dose is determined, the Phase 2 expansion portion will further evaluate the safety and efficacy of the combination in patients with different mutational subtypes, including BRAF Class 2 and 3 patients. ERAS-007 and ERAS-601 had favorable monotherapy safety and tolerability profiles with largely non-overlapping treatment-related adverse events that support combination development. Forty-four percent (4/9) of patients with BRAF-driven tumors responded (one confirmed and three unconfirmed PRs) to single agent ERAS-007 or ERAS-601, including three (one confirmed and two unconfirmed PRs) in tumors with BRAF Class 2 and 3 alterations.
The clinical data referred to above was presented at Erasca’s September 7, 2022 R&D Day, and consisted of a retrospective pooled interim analysis of monotherapy ERAS-007 and ERAS-601 data, with data cutoff dates of 11/6/20, 7/11/22, and 5/16/22 for the ASN007-101, FLAGSHP-1, and HERKULES-1 trials, respectively.
ERAS-007 is a potential best-in-class ERK1/2 inhibitor being investigated alone or in combination with different inhibitors targeting upstream nodes of the RAS/MAPK pathway as part of Erasca’s MAPKlamp strategy. The extracellular signal-regulated kinases (ERK), ERK1 and ERK2, belong to a family of serine-threonine kinases that regulate cellular signaling and comprise the terminal node of the RAS/MAPK pathway. ERAS-007 is being investigated across the series of HERKULES clinical trials that span multiple tumor types and includes both monotherapy and combinations with approved and investigational agents, such as RTK, SHP2, RAS, RAF, and/or cell cycle inhibitors. HERKULES-1 is a Phase 1b/2 clinical trial for ERAS-007 as a single agent and in combination with the SHP2 inhibitor ERAS-601 (together, Erasca’s first MAPKlamp) in advanced solid tumors. HERKULES-2 is a Phase 1b/2 master protocol clinical trial for ERAS-007 in combination with various agents in patients with non-small cell lung cancer (NSCLC). HERKULES-3 is a Phase 1b/2 master protocol clinical trial for ERAS-007 in combination with various agents in patients with gastrointestinal (GI) cancers.
ERAS-601 is a potential best-in-class oral, selective SHP2 inhibitor being investigated alone or in combination. SHP2 acts as a convergent node for receptor tyrosine kinase (RTK) signaling, relaying growth and survival signals from RTKs to intracellular signaling pathways. ERAS-601 combined with the ERK1/2 inhibitor ERAS-007 makes up Erasca’s first innovative MAPKlamp strategy. ERAS-601 is being investigated across a series of clinical trials that span multiple tumor types and include both monotherapy and combinations with approved and investigational agents. FLAGSHP-1 is a Phase 1/1b clinical trial evaluating ERAS-601 as a monotherapy in advanced solid tumors and in combination in triple wildtype (KRAS/NRAS/BRAF wildtype) CRC and human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC). HERKULES-1 is a Phase 1b/2 clinical trial that includes evaluation of ERAS-601 in combination with ERAS-007 in advanced solid tumors. HERKULES-2 is a Phase 1b/2 master protocol clinical trial that includes evaluation of ERAS-601 in combination with various agents in patients with non-small cell lung cancer (NSCLC).
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 what we believe to be 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.
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 ERAS-007 and ERAS-601, and their combination as part of our first MAPKlamp strategy; our expectations regarding the monotherapy data for ERAS-007 and ERAS-601 described in this press release being indicative of future clinical results; our beliefs regarding market sizes and opportunities; and the planned advancement of our development pipeline, including the clinical development plans for each of the HERKULES series of trials and the FLAGSHP-1 trial. 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: the retrospective analysis of pooled data referred to in this press release covers multiple clinical trials with different designs, inclusion criteria, and dosing regimens, which cannot be directly compared, and therefore may not be a reliable indicator of efficacy and safety data; interim results of clinical trials are not necessarily indicative of final results and one or more of the clinical outcomes may materially change as patient enrollment continues, following more comprehensive reviews of the data and more patient data become available; 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; delays in our preclinical and clinical development programs; our dependence on third parties to conduct 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; unfavorable results from preclinical studies or clinical trials; results from preclinical studies or early clinical trials not necessarily being predictive of future results; regulatory developments in the United States and foreign countries; our ability to obtain and maintain intellectual property protection for our product candidates and maintain our rights under intellectual property licenses; our ability to fund our operating plans with our current cash, cash equivalents, and marketable securities; our ability to maintain undisrupted business operations due to the COVID-19 pandemic and global geopolitical events, such as the ongoing conflict between Russia and Ukraine; unstable market and economic conditions having serious adverse consequences on our business, financial condition and stock price; and other risks described in our prior filings with the Securities and Exchange Commission (SEC), including under the heading “Risk Factors” in our most recent annual report on Form 10-K for the year ended December 31, 2021, 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.
LifeSci Advisors, LLC
Source: Erasca, Inc.