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

Overview

STX-721, also known as ST-5924, is an investigational, orally administered small molecule developed by Scorpion Therapeutics in collaboration with Pierre Fabre Laboratories. It targets epidermal growth factor receptor (EGFR) and ERBB2 (HER2) exon 20 insertion mutations, which are known oncogenic drivers in non-small cell lung cancer (NSCLC). (businesswire.com)

Mechanism of Action

STX-721 functions as a highly selective, irreversible tyrosine kinase inhibitor (TKI) designed to inhibit EGFR and HER2 exon 20 insertion mutations. Its selectivity aims to minimize off-target effects associated with wild-type EGFR inhibition, potentially reducing adverse events commonly observed with less selective therapies. (businesswire.com)

Clinical Development

As of October 2023, STX-721 entered a Phase 1/2 first-in-human clinical trial to evaluate its safety, tolerability, and efficacy in patients with locally advanced or metastatic NSCLC harboring EGFR exon 20 insertion mutations. The trial is a multi-center, open-label study focusing on dose escalation and expansion to determine the recommended Phase 2 dose. (businesswire.com)

Efficacy and Safety

Currently, there are no publicly available results from human clinical trials assessing the efficacy and safety of STX-721. Preclinical studies have demonstrated strong in vivo anti-tumor activity across various EGFR and HER2 exon 20 mutant models, with a favorable risk/benefit profile supporting clinical development. (1stoncology.com)

Further Reading

• Scorpion Therapeutics and Pierre Fabre Laboratories Announce First Patient Dosed in Phase 1/2 Clinical Trial of STX-721
• Scorpion Therapeutics to Present Preclinical Proof-of-Concept Data for Highly Selective, Next-Generation Exon 20 Mutant EGFR Inhibitor at 34th EORTC-NCI-AACR Symposium

Last updated: Apr 2025

Overview

STX-721, also known as ST-5924, is an investigational, orally administered small molecule developed by Scorpion Therapeutics in collaboration with Pierre Fabre Laboratories. It targets epidermal growth factor receptor (EGFR) and ERBB2 (HER2) exon 20 insertion mutations, which are known oncogenic drivers in non-small cell lung cancer (NSCLC). (businesswire.com)

Mechanism of Action

STX-721 functions as a highly selective, irreversible tyrosine kinase inhibitor (TKI) designed to inhibit EGFR and HER2 exon 20 insertion mutations. Its selectivity aims to minimize off-target effects associated with wild-type EGFR inhibition, potentially reducing adverse events commonly observed with less selective therapies. (businesswire.com)

Clinical Development

As of October 2023, STX-721 entered a Phase 1/2 first-in-human clinical trial to evaluate its safety, tolerability, and efficacy in patients with locally advanced or metastatic NSCLC harboring EGFR exon 20 insertion mutations. The trial is a multi-center, open-label study focusing on dose escalation and expansion to determine the recommended Phase 2 dose. (businesswire.com)

Efficacy and Safety

Currently, there are no publicly available results from human clinical trials assessing the efficacy and safety of STX-721. Preclinical studies have demonstrated strong in vivo anti-tumor activity across various EGFR and HER2 exon 20 mutant models, with a favorable risk/benefit profile supporting clinical development. (1stoncology.com)

Further Reading

• Scorpion Therapeutics and Pierre Fabre Laboratories Announce First Patient Dosed in Phase 1/2 Clinical Trial of STX-721
• Scorpion Therapeutics to Present Preclinical Proof-of-Concept Data for Highly Selective, Next-Generation Exon 20 Mutant EGFR Inhibitor at 34th EORTC-NCI-AACR Symposium

Last updated: Apr 2025

Overview

STX-721, also known as ST-5924, is an investigational, orally administered small molecule developed by Scorpion Therapeutics in collaboration with Pierre Fabre Laboratories. It targets epidermal growth factor receptor (EGFR) and ERBB2 (HER2) exon 20 insertion mutations, which are known oncogenic drivers in non-small cell lung cancer (NSCLC). (businesswire.com)

Mechanism of Action

STX-721 functions as a highly selective, irreversible tyrosine kinase inhibitor (TKI) designed to inhibit EGFR and HER2 exon 20 insertion mutations. Its selectivity aims to minimize off-target effects associated with wild-type EGFR inhibition, potentially reducing adverse events commonly observed with less selective therapies. (businesswire.com)

Clinical Development

As of October 2023, STX-721 entered a Phase 1/2 first-in-human clinical trial to evaluate its safety, tolerability, and efficacy in patients with locally advanced or metastatic NSCLC harboring EGFR exon 20 insertion mutations. The trial is a multi-center, open-label study focusing on dose escalation and expansion to determine the recommended Phase 2 dose. (businesswire.com)

Efficacy and Safety

Currently, there are no publicly available results from human clinical trials assessing the efficacy and safety of STX-721. Preclinical studies have demonstrated strong in vivo anti-tumor activity across various EGFR and HER2 exon 20 mutant models, with a favorable risk/benefit profile supporting clinical development. (1stoncology.com)

Further Reading

• Scorpion Therapeutics and Pierre Fabre Laboratories Announce First Patient Dosed in Phase 1/2 Clinical Trial of STX-721
• Scorpion Therapeutics to Present Preclinical Proof-of-Concept Data for Highly Selective, Next-Generation Exon 20 Mutant EGFR Inhibitor at 34th EORTC-NCI-AACR Symposium

Last updated: Apr 2025

As of April 30, 2025, the Phase 1/2 clinical trial NCT06043817, evaluating STX-721 in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations, is ongoing. The trial commenced in October 2023, with the first patient dosed at that time. (biospace.com)

Trial Initiation and Progress

The trial began with the dosing of the first patient in October 2023. In March 2024, the South Korean Ministry of Food and Drug Safety approved the trial, allowing its expansion to Seoul National University Hospital. (dailypharmkorea.com)

Preclinical Data and Drug Profile

Preclinical studies have indicated that STX-721 is a highly differentiated, orally bioavailable, irreversible, and highly selective tyrosine kinase inhibitor targeting EGFR and ERBB2 (HER2) exon 20 insertion mutations. The drug is designed to be mutant-selective, aiming to minimize adverse effects associated with wild-type EGFR inhibition. This selectivity is intended to provide a wider therapeutic window compared to existing therapies. (biospace.com)

Collaboration and Development

In April 2023, Scorpion Therapeutics and Pierre Fabre Laboratories entered into a collaboration to co-develop STX-721 and another EGFR-targeting agent, STX-241. Under this agreement, Pierre Fabre obtained rights to commercialize these drugs outside the US, Canada, and Japan, while Scorpion retained rights within these territories. (precisionmedicineonline.com)

Current Status

As of the latest available information, the trial is actively recruiting participants. The primary completion date is projected for June 2027. (veri.larvol.com)

Key References

• (biospace.com)
• (precisionmedicineonline.com)
• (dailypharmkorea.com)

Last updated: Apr 2025

Key Inclusion Criteria:

1. Has histologically- or cytologically confirmed diagnosis of NSCLC Stage IIIB/C or IV not eligible for curative intent surgery or chemoradiation

2. Part 1: Tumor tissue EGFR or HER2 exon 20 insertion mutations confirmed by qualified local laboratories. Parts 2 and 3: EGFR exon 20 insertion mutations confirmed by qualified local laboratories

3. Part 1: Has received all approved therapies for advanced or metastatic NSCLC or is ineligible. Part 2 and Part 3: Has received at least 1, but not more than 2, prior lines of treatment for advanced or metastatic NSCLC, 1 of which must be platinum-based chemotherapy unless contraindicated

4. Has documented tumor progression (based on radiological imaging)

5. Has new or recent tumor biopsy (collected at screening, if feasible) or archival tumor specimen collected in the past 10 years available for genomic profiling

6. Has at least one measurable tumor lesion per RECIST v1.1

7. Is ≥18 years of age at the time of signing the ICF

8. Has Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1

Key Exclusion Criteria:

1. Has a tumor that is known to harbor EGFR ex20ins p.H773_V774insH variant, or any EGFR kinase domain activating mutation concurrent with either a T790M and/or C797S resistance mutations

2. Has history (within ≤2 years before screening) of solid tumor or hematological malignancy that is histologically distinct from NSCLC

3. Has symptomatic brain or spinal metastases

4. Has toxicities from previous anticancer therapies that have not resolved to baseline levels or to CTCAE Grade ≤1, except for alopecia and peripheral neuropathy

5. Has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (e.g., could compromise the participant's well-being) or would prevent, limit, or confound the protocol-specified assessments