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

NCT06043817 | Recruiting Phase 1 FDA Drug

• 1 other identifier: STX-721-101/PFL-721CI101
• Study Type: interventional
• Target: 251
• Locations: 7 countries
• Sites: 24

Brief 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.

Conditions

Non-Small Cell Lung Cancer; NSCLC; EGFR/HER2 Exon 20 Insertion Mutation

Keywords

Exon 20, EGFR, HER2, NSCLC, TKI

Outcome Measures

Primary Outcomes (8)

• Part 1 Dose Escalation (MTD): Dose Escalation - Number of participants who experience at least 1 DLT during the first 28 days of treatment

  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

  28 days

• Part 2 RP2D Selection: C(max) of STX-721/PFL-721

  1 year

• Part 2 RP2D Selection: AUC(0-inf) of STX-721/PFL-721

  1 year

• Part 2 RP2D Selection: AUC(0-t) of STX-721/PFL-721

  1 year

• Part 2 RP2D Selection: AUC(0-τ) of STX-721/PFL-721

  1 year

• 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.

  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.

  1 year

Study Arms (3)

Part 1: Dose Escalation

EXPERIMENTAL

Drug: STX-721/PFL-721 (Escalated)

Part 2: RP2D Selection

EXPERIMENTAL

Drug: STX-721/PFL-721 (3 dose levels)

Part 3: Dose Expansion

EXPERIMENTAL

Drug: STX-721/PFL-721 (RP2D)

Interventions

STX-721/PFL-721 (Escalated) DRUG

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

Part 1: Dose Escalation

STX-721/PFL-721 (3 dose levels) DRUG

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

Part 2: RP2D Selection

STX-721/PFL-721 (RP2D) DRUG

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

Part 3: Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 approved 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Pierre Fabre Medicament: lead

Study Sites (24)

City of Hope

Duarte, California, 91010, United States

RECRUITING

City of Hope

Huntington Beach, California, 92648, United States

RECRUITING

City of Hope

Irvine, California, 92618, United States

RECRUITING

Levine Cancer Institute - Charlotte

Charlotte, North Carolina, 28204-2990, United States

RECRUITING

Thomas Jefferson University Research Facility

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

SCRI Oncology Partners - PPDS

Nashville, Tennessee, 37203, United States

RECRUITING

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030-4009, United States

RECRUITING

University of Utah - Huntsman Cancer Institute - PPDS

Salt Lake City, Utah, 84112-5550, United States

RECRUITING

NEXT Virginia

Fairfax, Virginia, 22031-2171, United States

RECRUITING

EDOG Institut de Cancerologie de l'Ouest - PPDS

Saint-Herblain, Loire-Atlantique, 44115, France

RECRUITING

Institut Claudius Regaud - PPDS

Toulouse, 31059, France

RECRUITING

Gustave Roussy

Villejuif, 94800, France

RECRUITING

Charité - Universitätsmedizin Berlin (CBF) - Hindenburgdamm 30

Berlin, 12203, Germany

RECRUITING

Universitätsklinikum Carl Gustav Carus an der TU Dresden

Dresden, 01307, Germany

RECRUITING

Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis

Amsterdam, 1066, Netherlands

RECRUITING

Chungbuk National University Hospital

Cheongju-si, 28644, South Korea

RECRUITING

CHA Bundang Medical Center, CHA University

Seongnam-si, 13496, South Korea

RECRUITING

Seoul National University Hospital

Seoul, 03080, South Korea

RECRUITING

Hospital Regional Universitario de Malaga - Hospital General

Málaga, Malaga, 29010, Spain

RECRUITING

Instituto de Investigacion Oncologica Vall dHebron (VHIO) - EPON

Barcelona, 8035, Spain

RECRUITING

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

RECRUITING

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

RECRUITING

National Taiwan University Hospital

Taipei, 10002, Taiwan

RECRUITING

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Floors and Floorcoverings

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Facility Design and Construction; Architecture; Technology, Industry, and Agriculture

Central Study Contacts

Adele De MASSON, clinical devlopment director, MD, PhD

CONTACT

33 772344916; PFL721_medical.team@pierre-fabre.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2023
• First Posted: September 21, 2023
• Study Start: September 26, 2023
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: April 24, 2026

Record last verified: 2026-04

Locations

DE (2); ES (4); KR (3); FR (3); US (9); NL (1); TW (2)