First-In-Human Study of STX-721/PFL-721 in Participants With Locally Advanced or Metastatic Non-Small Cell Lung Cancer Harboring EGFR or HER2 Exon 20 Insertion Mutations

Study Identifier:
STX-721-101/PFL721CI101
CT.gov Identifier:
NCT06043817
EudraCT Identifier:
202350675951
EU Trial (CTIS) Number:
2023-506759-51-00
Study Contact Information:
(210) 593-5651 or [email protected]
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Study Summary

Study STX-721-101 is an open label, Phase 1/2 study evaluating the safety, tolerability, pharmacokinetic (PK) exposure, and preliminary antitumor activity of STX-721 in participants with non-small cell lung cancer (NSCLC) carrying EGFR/HER2 exon 20 insertion (ex20ins) mutations. To characterize the safety profile of STX-721 and determine a maximum tolerated dose or a lower optimal-biologically active dose, if appropriate, as the recommended Phase 2 dose (“RP2D”) as a monotherapy for NSCLC driven by EGFR exon20ins mutations. To evaluate the safety, tolerability and overall efficacy of STX-721. To evaluate the safety, tolerability, pharmacokinetic (PK) exposure, and preliminary antitumor activity of PFL-721/STX-721 in participants with locally advanced or metastatic NSCLC harboring EGFR/HER2 ex20ins mutations. Biomarkers - ctDNA as a potential predictive biomarker of response - Other pharmacodynamic markers (blood) to assess target engagement - Optional pretreatment and post-treatment tumor biopsies to assess target engagement in the tumor microenvironment

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Non-Small Cell Lung Cancer
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
Phase I/II
Sex
Female & Male
Age
18 - 99 Years
Study Drug
Drug: Experimental: Part 1a: Dose EscalationDrug: STX-721/PFL-721 (Escalated)
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Drug: ASCO 2026:
Study Status
Indicates the current recruitment status or the expanded access status
Recruiting

Requirements information
Inclusion criteria
  • Has histologically- or cytologically confirmed diagnosis of NSCLC Stage IIIB/C or IV not eligible for curative intent surgery or chemoradiationPart 1: Tumor tissue EGFR or HER2 exon 20 insertion mutations confirmed by qualified local laboratories. Parts 2 and 3: EGFR/HER2 exon 20 insertion mutations confirmed by qualified local laboratoriesPart 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 approved treatment for advanced or metastatic NSCLC, 1 of which must be platinum-based chemotherapy unless contraindicatedHas documented tumor progression (based on radiological imaging)Has new or recent tumor biopsy (collected at screening, if feasible) or archival tumor specimen collected in the past 10 years available for genomic profilingHas at least one measurable tumor lesion per RECIST v1.1Is ≥18 years of age at the time of signing the ICFHas Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
Exclusion criteria
  • 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
  • Has history (within ≤2 years before screening) of solid tumor or hematological malignancy that is histologically distinct from NSCLC
  • Has symptomatic brain or spinal metastases
  • Has toxicities from previous anticancer therapies that have not resolved to baseline levels or to CTCAE Grade ≤1, except for alopecia and peripheral neuropathy
  • 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
  • relevant comorbidites
  • unable or unwilling to give written informed consent

Clinical Study Information for Healthcare Providers

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Study Locations

Location
Investigator
Status
Condition(s) Treated at Site
Location
START New Jersey
East Brunswick, NJ, United States, 08816
Investigator
Bruno Fang
Status
Recruiting
Condition(s) Treated at Site
Non-Small Cell Lung Cancer