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

August 31, 2026 updated by: Pierre Fabre Medicament
Study STX-721-101/PFL-721CI101 is an open label, Phase 1/2 study evaluating the safety, tolerability, pharmacokinetic (PK) exposure, and preliminary antitumor activity of STX-721/PFL-721 in participants with non-small cell lung cancer (NSCLC) carrying EGFR or HER2 exon 20 insertion (ex20ins) mutations.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

345

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • France
      • Toulouse, France, 31059
        • Recruiting
        • Institut Claudius Regaud - PPDS
      • Villejuif, France, 94800
        • Recruiting
        • Gustave Roussy
    • Loire-Atlantique
      • Saint-Herblain, Loire-Atlantique, France, 44115
        • Recruiting
        • EDOG Institut de Cancerologie de l'Ouest - PPDS
  • Germany
      • Berlin, Germany, 12203
        • Recruiting
        • Charité - Universitätsmedizin Berlin (CBF) - Hindenburgdamm 30
      • Dresden, Germany, 01307
        • Recruiting
        • Universitätsklinikum Carl Gustav Carus an der TU Dresden
  • Netherlands
      • Amsterdam, Netherlands, 1066
        • Recruiting
        • Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis
  • South Korea
      • Cheongju-si, South Korea, 28644
        • Recruiting
        • Chungbuk National University Hospital
      • Seongnam-si, South Korea, 13496
        • Recruiting
        • CHA Bundang Medical Center, CHA University
      • Seoul, South Korea, 03080
        • Recruiting
        • Seoul National University Hospital
  • Spain
      • Barcelona, Spain, 8035
        • Recruiting
        • Instituto de Investigacion Oncologica Vall dHebron (VHIO) - EPON
      • Madrid, Spain, 28034
        • Recruiting
        • Hospital Universitario Ramón y Cajal
      • Seville, Spain, 41013
        • Recruiting
        • Hospital Universitario Virgen del Rocío
    • La Rioja
      • Logroño, La Rioja, Spain, 26006
        • Recruiting
        • START - Rioja Hospital Universitario San Pedro
    • Malaga
      • Málaga, Malaga, Spain, 29010
        • Recruiting
        • Hospital Regional Universitario de Malaga - Hospital General
  • Taiwan
      • Taipei, Taiwan, 10002
        • Recruiting
        • National Taiwan University Hospital
      • Taipei, Taiwan, 11217
        • Recruiting
        • Taipei Veterans General Hospital
  • United States
    • California
      • Duarte, California, United States, 91010
        • Recruiting
        • City of Hope
      • Huntington Beach, California, United States, 92648
        • Recruiting
        • City of Hope
      • Irvine, California, United States, 92618
        • Recruiting
        • City of Hope
    • North Carolina
      • Charlotte, North Carolina, United States, 28204-2990
        • Recruiting
        • Levine Cancer Institute - Charlotte
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Recruiting
        • Thomas Jefferson University Research Facility
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Recruiting
        • SCRI Oncology Partners - PPDS
    • Texas
      • Houston, Texas, United States, 77030-4009
        • Recruiting
        • University of Texas MD Anderson Cancer Center
    • Utah
      • Salt Lake City, Utah, United States, 84112-5550
        • Recruiting
        • University of Utah - Huntsman Cancer Institute - PPDS
    • Virginia
      • Fairfax, Virginia, United States, 22031-2171
        • Recruiting
        • NEXT Virginia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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/HER2 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 approved 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part 1: Dose Escalation
Drug: STX-721/PFL-721 (Escalated)
STX-721/PFL-721 dose will be escalated per cBLRM-design.
Experimental: Part 2: RP2D Selection
Drug: STX-721/PFL-721 (3 dose levels)
Participants will receive STX-721/PFL-721 at one of three dose levels.
Experimental: Part 3: Dose Expansion
Drug: STX-721/PFL-721 (RP2D)
Participants will receive the RP2D of STX-721/PFL-721.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Part 1 Dose Escalation (MTD): Dose Escalation - Number of participants who experience at least 1 DLT during the first 28 days of treatment
Time Frame: 28 days
28 days
Part 1 Dose Escalation (OBD): Dose Escalation - Number of participants who experience at least 1 DLT during the first 28 days of treatment
Time Frame: 28 days
28 days
Part 2 RP2D Selection: Number of participants with confirmed objective response rate (ORR) defined as the percentage of participants with partial response (PR) or complete response (CR) based on RECIST v1.1 per investigator assessment.
Time Frame: 1 year
1 year
Part 2 RP2D Selection: C(max) of STX-721/PFL-721
Time Frame: 1 year
1 year
Part 2 RP2D Selection: AUC(0-inf) of STX-721/PFL-721
Time Frame: 1 year
1 year
Part 2 RP2D Selection: AUC(0-t) of STX-721/PFL-721
Time Frame: 1 year
1 year
Part 2 RP2D Selection: AUC(0-τ) of STX-721/PFL-721
Time Frame: 1 year
1 year
Part 3 Dose Expansion: Number of participants with confirmed ORR defined as the percentage of participants with PR or CR based on RECIST v1.1 per investigator assessment.
Time Frame: 1 year
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Pierre Fabre Medicament

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 26, 2023

Primary Completion (Estimated)

December 1, 2029

Study Completion (Estimated)

December 1, 2029

Study Registration Dates

First Submitted

September 1, 2023

First Submitted That Met QC Criteria

September 18, 2023

First Posted (Actual)

September 21, 2023

Study Record Updates

Last Update Posted (Actual)

September 2, 2026

Last Update Submitted That Met QC Criteria

August 31, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STX-721-101/PFL-721CI101

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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