STX-241 Trial Begins for EGFR TKI-Resistant NSCLC Treatment

Illustration of lungs: © yodiyim - stock.adobe.com

A phase 1/2 trial (NCT06567015) evaluating STX-241 (PFL-241) for the treatment of EGFR inhibitor-resistant non–small cell lung cancer (NSCLC) has dosed its first patient.¹

"We are eager to begin the clinical evaluation of PFL-241/STX-241, our mutant-selective fourth generation EGFR inhibitor, a molecule with differentiated properties that we believe has the potential to become a best-in-class therapeutic option for patients developing resistance to current targeted therapy," said Francesco Hofmann, head of research and development for medical care at Pierre Fabre Laboratories, in a press release. "The initiation of this clinical trial highlights our team's engagement and execution in strong partnership with Scorpion Therapeutics, and we look forward to demonstrating how patients could potentially benefit from this targeted therapy."

STX-241 is a highly differentiated, orally bioavailable, highly selective tyrosine kinase inhibitor (TKI) targeting EGFR exon 19 or 21 mutations with a co-occurring C797S mutation, which is a resistance mechanism to third generation EGFR inhibitors. EGFR mutations occur in up to 38% of tumors, depending on geography.

In part 1, the dose-escalation part of the study, patients will receive STX-241 orally twice daily at fixed doses of 10 mg, 20 mg, 40 mg, 80 mg, 120 mg, or 180 mg on a continuous dosing schedule. In part 2, the dose range optimization portion of the study, patients will receive STX-241 twice daily at fixed doses selected from part 1 on a continuous dosing schedule. The dose-escalation portion, part 3, will administer STX-241 at the recommended phase 2 dose.²

Parts 1 and 2 of the study will evaluate safety and tolerability of the agent, along with pharmacokinetics, disease control rate, time to response, and duration of response.² Part 1 will also identify the maximum tolerated dose and optimal biologically active dose of STX-241. In part 2, investigators will aim to identify the recommended phase 2 dose and overall response rate.

Patients with histologically confirmed locally advanced or metastatic NSCLC with an EGFR exon 19 deletion or L858R mutation who experienced disease progression on a third generation EGFR TKI are eligible for enrollment. Patients must also have an ECOG performance status of 0 or 1, adequate organ function, and adequate cardiac function to be eligible for the study. Those with a history of other malignancies, uncontrolled central nervous system metastases, active infection, or impaired cardiovascular function are not eligible for enrollment.

The study has an estimated enrollment of 171 across 14 locations in the US, France, China, Germany, the Netherlands, Spain, and Taiwan.

REFERENCES:

1. Pierre Fabre Laboratories and Scorpion Therapeutics announce first patient dosed in phase I/II clinical trial of PFL-241/STX-241, a mutant-selective inhibitor intended to treat locally advanced or metastatic non-small cell lung cancer. News release. Pierre Fabre Laboratories. October 8, 2024. Accessed October 8, 2024. https://tinyurl.com/5n82hmj2

2. Study of FIH of STX-241 in locally advanced or metastatic NSCLC resistant to EGFR TKIs (STX-241 FIH). ClinicalTrials.gov. Updated October 7, 2024. Accessed October 8, 2024. https://clinicaltrials.gov/study/NCT06567015