A first-in-human trial is assessing the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of STX-721 as a monotherapy for patients with non–small cell lung cancer with EGFR exon 20 insertion mutations.
Trial Name: First-In-Human Study of STX-721 in Participants With Locally Advanced or Metastatic Non-Small Cell Lung Cancer Harboring EGFR Exon 20 Insertion Mutations
ClinicalTrials.gov Identifier: NCT06043817
Sponsor: Scorpion Therapeutics, Inc.
Recruitment Contact: clinicaltrials@scorpiontx.com
Completion Date: May 1, 2028
The first patient has been dosed with STX-721 in a phase 1/2, first-in-human dose-escalation and dose-expansion trial (NCT06043817) for patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion (ex20ins) mutations, according to Scorpion Therapeutics, Inc.1
STX-721 is a highly differentiated, orally bioavailable, irreversible highly selective tyrosine kinase inhibitor (TKI) which targets the EGFR and ERBB2 ex20ins mutations. The agent is designed to be mutant-selective and is made for tolerability and efficacy.
The phase 1/2 trial plans to assess the safety, tolerability, pharmacokinetic (PK) exposure, and preliminary antitumor activity of STX-721 as a monotherapy in this patient population.
"We are excited to begin the clinical evaluation of STX-721, our mutant-selective EGFR ex20ins inhibitor with a potentially best-in-class profile, for the treatment of non-small cell lung cancer," said Axel Hoos, MD, PhD, chief executive officer of Scorpion Therapeutics, Inc., in a press release. "The initiation of our second clinical trial this year underscores our research team's productivity and execution, as well as the confidence that Scorpion and Pierre Fabre Laboratories have in the quality, selectivity, and potential clinical differentiation of this compound. Based on preclinical data to-date, we believe that STX-721 is more selective and can provide a wider therapeutic window than other therapies currently on the market or in development and, as a result, has the potential to deliver superior efficacy to this highly underserved patient population."
In the phase 1/2 trial between Scorpion and Pierre Fabre Laboratories, the safety and tolerability of STX-721 is being evaluated in patients with NSCLC driven by EGFR mutations. The multicenter, open-label study will give patients multiple ascending doses of STX-721 to characterize the safety profile of STX-721 and determine a maximum tolerated dose.2
Part 1 will be the dose-escalation portion of the study, part 2 will utilize the recommended phase 2 dose (RP2D) of STX-721 determined in part 1, and part 3 will be the dose-expansion portion. Once the RP2D is established in the first phase of the study, investigators will continue to evaluate the safety, tolerability, and efficacy of STX-721.
Enrollment is open to patients aged 18 years and older with a histologically or cytologically confirmed diagnosis of NSCLC by stage IIIB/C or IV not eligible for curative intent surgery or chemoradiation, tumor tissue EGFR ex20ins mutations confirmed by local laboratories, new or recent tumor biopsy, and an ECOG performance status of 0 or 1.
For part 1, the primary end point is to assess dose-limiting toxicities. The primary end points in part 2 are PK and overall response rate (ORR), and in part 3, the primary end point is ORR. Secondary objectives for this Phase 1/2 trial include assessing the pharmacokinetic profile, pharmacodynamic effects and clinical response as measured by RECIST v1.1.
"We are pleased to see STX-721 enter the clinic, and the overall progress we've achieved since we announced the partnership with Scorpion 6 months ago," said Eric Ducournau, chief executive officer of Pierre Fabre Laboratories, in a press release.1 "Our 2 teams have been working closely on both of the EGFR candidates and we look forward to seeing how patients may benefit from this targeted therapy."
"STX-721 is a wild-type-sparing, oral inhibitor of EGFR ex20ins mutations with a compelling preclinical selectivity profile," added Michael Streit, MD, chief medical officer of Scorpion, in the press release. "In this phase 1/2 trial, we will aim to demonstrate how these unique qualities translate into a potentially best-in-class product profile that increases response rates as a result of its optimized design. We look forward to partnering with study investigators, as well as our colleagues at Pierre Fabre Laboratories, to evaluate STX-721 in patients with EGFR ex20ins-mutated NSCLC."
