Erasca has entered into a clinical trial collaboration and supply agreement with Eli Lilly and Company to evaluate the anti-EGFR antibody cetuximab.
A clinical trial collaboration and supply agreement (CTCSA) between Erasca, Inc and Eli Lilly and Company will evaluate the anti-EGFR antibody cetuximab (Erbitux), supporting the ongoing phase 1/1b FLAGSHP-1 trial (NCT04670679) examining ERAS-601, an oral SHP2 inhibitor in combinations, including for the treatment of triple wild-type (KRAS/NRAS/BRAF wild-type) metastatic colorectal cancer (CRC) and human papillomavirus (HPV)-negative advanced head and neck squamous cell carcinoma (HNSCC).1
Erasca previously signed CTCSAs with Lilly and Pfizer to evaluate cetuximab and encorafenib (Braftovi) in combination with Erasca’s ERK1/2 inhibitor, ERAS-007, as part the HERKULES-3 phase 1b/2 trial (NCT05039177). Erasca is the sponsor of this trial, and Lilly will supply cetuximab at no cost.
“We are pleased to enter another clinical trial collaboration with Lilly to explore cetuximab in combination with ERAS-601, our SHP2 inhibitor, in EGFR-driven cancers that are highly dependent on RAS/MAPK signaling,” said Jonathan E. Lim, MD, chairman, chief executive officer, and co-founder of Erasca, in a press release. “Dual inhibition of EGFR and SHP2, a convergent RTK signaling node, has the potential to broaden and deepen responses relative to cetuximab monotherapy and delay onset of resistance in cancers like triple wildtype metastatic CRC and HPV-negative advanced HNSCC.”
The FLAGSHIP-1 trial is an open-label, multicenter clinical study of ERAS-601 as a monotherapy and in combination with other therapies. The trial consists of 4 parts. Part A is a dose-escalation where patients will receive oral ERAS-601 monotherapy, part B is a dose-escalation where patients with receive ERAS-601 in combination with intravenous cetuximab, part C is dose-expansion with ERAS-601 monotherapy based off part A, and part D is a dose-expansion with ERAS-601 and cetuximab combination based off part B. Investigators will measure dose-limiting toxicities, maximum tolerated dose, recommended dose, adverse events, plasma concentration (Cmax), and time to Cmax. Secondary end points include objective response rate, duration of response, and time to response.2
To be included in the study, patients must be at least 18 years of age, have a histologically or cytologically confirmed advanced or metastatic solid tumor, and had no standard systemic therapy for the tumor histology and/or molecular biomarker profile. Patients must also be able to swallow oral medication, have an ECOG performance score of 0 or 1, have adequate cardiovascular, hematological, liver, and renal function.
Patients with previous treatment with a SHP2 inhibitor, documented PTPN11 mutations, or are currently receiving another study therapy or have participated in a study of an investigational agent and received study therapy within 4 weeks of the first dose of ERAS-601 will be ineligible for participation. Other exclusionary criteria include those who have received prior palliative radiation within 7 days of cycle 1, day 1, have primary central nervous system (CNS) disease or known active CNS metastases and/or carcinomatous meningitis, have had prior surgery or gastrointestinal dysfunction that may affect drug absorption, have clinically significant interstitial lung disease or pneumonitis, a history of thromboembolic or cerebrovascular events within 12 weeks prior to the first dose of study treatment, or a history or current evidence of retinal vein occlusion.2