RecruitingPhase 1Phase 2NCT06043817

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


Sponsor

Pierre Fabre Medicament

Enrollment

251 participants

Start Date

Sep 26, 2023

Study Type

INTERVENTIONAL

Summary

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.


Eligibility

Min Age: 18 Years

Inclusion Criteria8

  • Has histologically- or cytologically confirmed diagnosis of NSCLC Stage IIIB/C or IV not eligible for curative intent surgery or chemoradiation
  • 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
  • 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
  • Has 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 profiling
  • Has at least one measurable tumor lesion per RECIST v1.1
  • Is ≥18 years of age at the time of signing the ICF
  • Has Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1

Exclusion Criteria5

  • 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

Interventions

DRUGSTX-721/PFL-721 (Escalated)

STX-721/PFL-721 dose will be escalated per cBLRM-design.

DRUGSTX-721/PFL-721 (3 dose levels)

Participants will receive STX-721/PFL-721 at one of three dose levels.

DRUGSTX-721/PFL-721 (RP2D)

Participants will receive the RP2D of STX-721/PFL-721.


Locations(24)

City of Hope

Duarte, California, United States

City of Hope

Huntington Beach, California, United States

City of Hope

Irvine, California, United States

Levine Cancer Institute - Charlotte

Charlotte, North Carolina, United States

Thomas Jefferson University Research Facility

Philadelphia, Pennsylvania, United States

SCRI Oncology Partners - PPDS

Nashville, Tennessee, United States

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

University of Utah - Huntsman Cancer Institute - PPDS

Salt Lake City, Utah, United States

NEXT Virginia

Fairfax, Virginia, United States

EDOG Institut de Cancerologie de l'Ouest - PPDS

Saint-Herblain, Loire-Atlantique, France

Institut Claudius Regaud - PPDS

Toulouse, France

Gustave Roussy

Villejuif, France

Charité - Universitätsmedizin Berlin (CBF) - Hindenburgdamm 30

Berlin, Germany

Universitätsklinikum Carl Gustav Carus an der TU Dresden

Dresden, Germany

Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis

Amsterdam, Netherlands

Chungbuk National University Hospital

Cheongju-si, South Korea

CHA Bundang Medical Center, CHA University

Seongnam-si, South Korea

Seoul National University Hospital

Seoul, South Korea

Hospital Regional Universitario de Malaga - Hospital General

Málaga, Malaga, Spain

Instituto de Investigacion Oncologica Vall dHebron (VHIO) - EPON

Barcelona, Spain

Hospital Universitario Ramon y Cajal

Madrid, Spain

Hospital Universitario Virgen del Rocio

Seville, Spain

National Taiwan University Hospital

Taipei, Taiwan

Taipei Veterans General Hospital

Taipei, Taiwan

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NCT06043817