STX-721 for Non-Small Cell Lung Cancer

Recruiting at 23 trial locations

Overseen By For questions concerning enrollment

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Scorpion Therapeutics, Inc.

Disqualifiers: EGFR mutations, Brain metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

185 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a new treatment, STX-721, for individuals with non-small cell lung cancer (NSCLC) that has specific genetic mutations (EGFR/HER2 exon 20 insertion mutations). The goal is to assess the safety and tolerability of the treatment and determine its effectiveness in shrinking or controlling tumors. The trial consists of three parts to test different doses and evaluate their effects. Individuals with advanced lung cancer, who have previously tried standard treatments without success, may be suitable candidates. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It is best to discuss this with the trial team or your doctor.

Is there any evidence suggesting that STX-721 is likely to be safe for humans?

Research shows that STX-721 is designed as a more focused treatment for non-small cell lung cancer with certain mutations. Studies suggest that this treatment might cause fewer side effects than other similar drugs because it targets cancer cells more precisely, potentially sparing healthy cells. The treatment remains in early testing, so complete safety information is not yet available. However, researchers are closely monitoring its safety and patient tolerance during these initial stages to ensure the treatment is as safe as possible before advancing to the next phase. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for non-small cell lung cancer?

Unlike the standard treatments for non-small cell lung cancer, which often include chemotherapy and targeted therapies like EGFR inhibitors, STX-721 is unique because it introduces a novel mechanism of action. This treatment is designed to target specific cellular pathways that current options do not address. Researchers are excited about STX-721 because it has the potential to overcome resistance to existing therapies, offering hope for improved outcomes in patients who have few effective options left. Additionally, its ability to precisely target cancer cells may lead to fewer side effects compared to traditional treatments.

What evidence suggests that STX-721 might be an effective treatment for non-small cell lung cancer?

Research shows that STX-721 is a promising treatment for non-small cell lung cancer (NSCLC) with specific genetic changes. It targets certain mutations in the EGFR/HER2 genes that current medications struggle to treat. Studies indicate that STX-721 effectively blocks these mutations. Importantly, it appears to work well without significantly affecting normal cells, potentially leading to fewer side effects. Early evidence suggests it might be more effective at stopping cancer cell growth compared to other similar treatments. Participants in this trial will receive STX-721 in different phases, including dose escalation, RP2D selection, and dose expansion, to evaluate its safety and effectiveness. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with advanced non-small cell lung cancer (NSCLC) that can't be treated with surgery or chemoradiation and have specific EGFR exon 20 mutations. Participants should be relatively healthy, with a performance status showing they can carry out daily activities with little or no help.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

My tumor has a specific genetic change known as EGFR exon 20 insertion.

I have a recent or archived tumor sample from the last 10 years for testing.

Exclusion Criteria

I have cancer that has spread to my brain or spine and is causing symptoms.

My tumor has specific mutations known as T790M and C797S.

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.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of STX-721 to evaluate safety and tolerability

8-12 weeks

RP2D Selection

Participants receive the recommended Phase 2 dose (RP2D) to further assess safety and pharmacokinetics

8-12 weeks

Dose Expansion

Participants receive the RP2D to evaluate preliminary antitumor activity

12-16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• STX-721

Trial Overview STX-721 is being tested in this study to see if it's safe and how well it works against NSCLC with certain genetic changes. Patients will receive different doses of STX-721, including increased amounts to find the right dose, followed by a phase where everyone gets the best dose found.

How Is the Trial Designed?

Group I: Part 3: Dose Expansion Experimental Treatment 1 Intervention

Group II: Part 2: RP2D Selection Experimental Treatment 1 Intervention

Group III: Part 1: Dose Escalation Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Scorpion Therapeutics, Inc.

Lead Sponsor

Trials

2

Recruited

520+

Antares Therapeutics, Inc

Lead Sponsor

Published Research Related to This Trial

A new orthotopic non-small-cell lung cancer (NSCLC) mouse model was successfully established, allowing for effective testing of therapies, including lipid-based nanoparticles.

Lipid-based nanoparticles containing Br-C16-DX significantly improved survival outcomes compared to Taxotere, with 35 days longer progression-free survival and 27 days longer median survival, indicating their potential as a more effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of a novel orthotopic non-small cell lung cancer model and therapeutic benefit of 2'-(2-bromohexadecanoyl)-docetaxel conjugate nanoparticles. Peng, L., Feng, L., Yuan, H., et al.[2021]

Detection of FGFR1 mRNA is a more reliable predictor of response to FGFR inhibitors in lung squamous cell carcinoma (SqCC) than simply measuring FGFR1 gene amplification, based on patient-derived xenograft (PDX) models.

Combining FGFR tyrosine kinase inhibitors with cisplatin significantly enhances tumor cell death and prolongs survival in animal models, suggesting a promising treatment strategy for patients with FGFR1-overexpressing non-small cell lung cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cisplatin Increases Sensitivity to FGFR Inhibition in Patient-Derived Xenograft Models of Lung Squamous Cell Carcinoma. Weeden, CE., Holik, AZ., Young, RJ., et al.[2020]

Monoclonal antibody NJ001 significantly inhibits the migration and invasiveness of human lung adenocarcinoma cells, reducing their invasive activity by 65%.

The mechanism of action involves the upregulation of tissue inhibitor of matrix metalloproteinase-3 (TIMP-3) through direct transcriptional regulation of FOXP1, suggesting potential clinical applications for NJ001 in preventing and treating metastatic lung adenocarcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MAb NJ001 inhibits lung adenocarcinoma invasiveness by directly regulating TIMP-3 promoter activity via FOXP1 binding sites. Gu, C., Luo, Y., Zhang, S., et al.[2021]

Squamous cell lung cancer (sqCLC) is challenging to treat due to factors like older patient age, late-stage diagnosis, and high comorbidity rates, leading to median survival times of only 9 to 11 months.

Recent advancements in targeted therapies, including monoclonal antibodies and immunotherapies, have shown modest survival benefits for sqCLC patients, highlighting the need for ongoing research into actionable molecular targets and effective treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incremental Innovation and Progress in Advanced Squamous Cell Lung Cancer: Current Status and Future Impact of Treatment. Langer, CJ., Obasaju, C., Bunn, P., et al.[2018]

In a study of 41 patients with unresectable stage III non-small-cell lung cancer, the combination of oral S-1 and cisplatin with thoracic radiotherapy resulted in a high objective response rate of 87.8%, indicating strong efficacy.

The treatment also demonstrated favorable safety profiles, with manageable hematological toxicities and only mild non-hematological side effects, suggesting it could be a promising option for patients with locally advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of oral S-1 and cisplatin with concurrent radiotherapy for locally advanced non-small-cell lung cancer. Kaira, K., Tomizawa, Y., Yoshino, R., et al.[2013]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06043817

NCT06043817 | First-In-Human Study of STX-721 ... Study STX-721-101 is an open label, Phase 1/2 study evaluating the safety, tolerability, pharmacokinetic (PK) exposure, and preliminary antitumor activity of ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS3173

Trial in progress: First-in-human study of PFL-721/STX- ... In addition, PFL-721/STX-721 has demonstrated superior anti-proliferation and antitumor effects compared to other investigational anti-EGFR ...

3. pubs.acs.org pubs.acs.org/doi/10.1021/acs.jmedchem.4c02377

Discovery of STX-721, a Covalent, Potent, and Highly ... STX-721 (53) is a potent, irreversible inhibitor of the majority of EGFR/HER2 ex20ins mutants and demonstrates excellent mutant vs wild-type selectivity both ...

4. targetedonc.com targetedonc.com/view/phase-1-2-study-of-stx-721-doses-first-patient-with-egfr-exon-20-nsclc

Phase 1/2 Study of STX-721 Doses First Patient With ... A first-in-human trial is assessing the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of STX-721 as a monotherapy ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12260510/

STX-721, a Covalent EGFR/HER2 Exon 20 Inhibitor, Utilizes ... These data suggest that STX-721 may be less prone to WT EGFR–driven adverse events that have limited the efficacy of other EGFR ex20ins inhibitors and therefore ...

6. aacrjournals.org aacrjournals.org/clincancerres/article/31/14/3002/763499/STX-721-a-Covalent-EGFR-HER2-Exon-20-Inhibitor

STX-721, a Covalent EGFR/HER2 Exon 20 Inhibitor, Utilizes ... These data suggest that STX-721 may be less prone to WT EGFR–driven adverse events that have limited the efficacy of other EGFR ex20ins inhibitors and therefore ...