On May 25, 2023 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, reported preliminary Phase 1b data for ERAS-007 combinations in patients with GI malignancies from two poster presentations at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, Illinois (Press release, Erasca, MAY 25, 2023, View Source [SID1234639355]). The posters will be available online at Erasca.com/science/presentations.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"Early clinical data from HERKULES-3 continue to reinforce the potential to combine ERAS-007 with multiple agents and its potential as a backbone therapy to treat patients with GI malignancies. Importantly, these preliminary findings support a data-driven approach to refine the focus of our initial clinical development efforts on indications holding significant promise," said Jonathan E. Lim, M.D., Erasca’s chairman, CEO, and co-founder. "Our initial evaluation of the ERAS-007 + EC combination in patients with BRAF-mutated metastatic CRC will focus on EC-naïve patients based on the preliminary activity observed in HERKULES-3. By evaluating efficacy and safety in a larger sample size of patients treated at the 100 mg BID-QW dose of ERAS-007 with EC, we believe we will be able to better assess whether the promising response rate and duration of treatment observed with the triplet can be maintained."
Poster Presentation Highlights
Abstract 3557 – Preliminary results from ERAS-007 plus encorafenib and cetuximab (EC) in patients (pts) with metastatic BRAF V600E-mutated colorectal cancer (CRC) in HERKULES-3 study: A phase 1b/2 study of agents targeting the mitogen-activated protein kinase (MAPK) pathway in pts with advanced gastrointestinal malignancies (GI cancers)
ERAS-007 in combination with encorafenib (BRAFTOVI) + cetuximab (ERBITUX) demonstrated promising preliminary clinical activity in EC-naïve patients with metastatic BRAF V600E-mutated CRC. EC is currently approved for the treatment of patients with metastatic BRAF V600E-mutated CRC, as detected by an FDA-approved test, after prior therapy; however, only approximately 20% of patients experience an objective response in the second and later line of treatment setting. Downstream ERK inhibition through ERAS-007 may prevent resistance to upstream BRAF/EGFR inhibition when combined with EC. As of the data cutoff date of March 23, 2023:
40% (2/5) response rate and 60% (3/5) disease control rate (complete response + partial response + stable disease) in EC-naïve response evaluable patients at the highest dose of ERAS-007 tested (100 mg BID-QW), with duration of exposure for both responders > 34 weeks as of the data cutoff date; across all dose levels in EC-naïve response evaluable patients, 29% (2/7) response rate and 57% (4/7) disease control rate
ERAS-007 + EC was generally well-tolerated with mostly low-grade adverse events at all combination doses tested
One dose-limiting toxicity (DLT) was reported for ERAS-007 100 mg BID-QW + EC (Grade 3 macular edema)
Pharmacokinetic (PK) exposures of ERAS-007, encorafenib, and cetuximab were comparable to monotherapy values, suggesting no clinically significant PK drug-drug interactions between the study drugs
Additional HERKULES-3 Phase 1b combination data in EC-naïve patients with BRAF-mutated CRC expected between H2 2023 and H1 2024
Abstract 3558 – Preliminary results from ERAS-007 plus palbociclib (palbo) in patients (pts) with KRAS/NRAS mutant (m) colorectal cancer (CRC) or KRASm pancreatic ductal adenocarcinoma (PDAC) in HERKULES-3 study: A phase 1b/2 study of agents targeting the mitogen-activated protein kinase (MAPK) pathway in pts with advanced gastrointestinal malignancies (GI cancers)
ERAS-007 in combination with palbociclib (IBRANCE) demonstrated a lack of clinical activity in patients with KRAS/NRAS mutant CRC and KRAS mutant PDAC. Palbociclib is indicated for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer in combination with an aromatase inhibitor as initial endocrine based therapy or with fulvestrant in patients with disease progression following endocrine therapy. Based on these data, the combination of ERAS-007 and palbociclib will not be pursued further in this patient population.
Dr. Lim continued, "Our pioneering efforts exploring the potential of targeting adjacent pathways with terminal node inhibition of the RAS/MAPK pathway (ERAS-007) and cell cycle inhibition (palbociclib) did not demonstrate clinical activity in the initial evaluation. While we will not pursue further development of this combination in this patient population, it has contributed to our understanding and characterization of ERAS-007."