Study of FIH of STX-241 in Locally Advanced or Metastatic NSCLC Resistant to EGFR TKIs

NCT06567015 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: F60087CI1012023-510203-21-00
• Study Type: interventional
• Target: 171
• Locations: 7 countries
• Sites: 16

Brief Summary

The goal of this First-In-Human (FIH) Phase I/II trial is to establish the safety profile, determine the Recommended Phase II Dose (RP2D), explore the pharmacokinetic (PK) exposure and pharmacodynamic (PD) properties as well as assess the efficacy of STX-241/PFL-241, a mutant selective Central Nervous System (CNS)-penetrant fourth generation EGFR TKI, in participants with locally advanced or metastatic NSCLC that progressed during or following third generation EGFR TKI such as osimertinib due to C797X double acquired (secondary) mutations.

Conditions

Non-small Cell Lung Cancer (NSCLC)

Keywords

non-small cell lung cancer

Outcome Measures

Primary Outcomes (6)

• Safety: Part 1 and Part 2: Safety: Incidence and severity of treatment emergent adverse events (TEAEs)/serious adverse events (SAEs), according to NCI-CTCAE v5.0 criteria.

  Screening to Safety Follow-up (30 days post last dose)

• Part 1 and Part 2: Tolerability: Incidence of TEAEs/SAEs leading to STX-241 dose reductions, interruptions or discontinuations.

  Screening to Safety Follow-up (30 days post last dose)

• Part 1: Maximum Tolerated Dose (MTD): Incidence of Dose-Limiting Toxicities (DLTs)

  From first STX-241 intake until 28 days post first dose (28 days post first dose)

• Part 1: Optimal Biologically Active Dose (OBD)

  From the first STX-241 intake up to 24 months

• Part 2: Recommended Phase II Dose (RP2D) of STX-241

  From the first STX-241 intake up to 24 months

• Part 2: cORR (Confirmed Overall Response Rate) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 per investigator.

  Up to 24 months

Secondary Outcomes (18)

• All Parts: PK exposure parameter: Maximum Plasma Concentration (Cmax)

  Part 1 and Part 2: C1 Day 1, Day 2, Day 15; C2 Day 1; C3 Day 1; - each cycle is 28 days

• All Parts: PK exposure parameter: Time To Maximum Plasma Concentration (Tmax)

  Part 1 and Part 2: C1 Day 1, Day 2, Day 15; C2 Day 1; C3 Day 1; - each cycle is 28 days

• All Parts: PK exposure parameter: Area Under The Plasma Concentration-Time Curve From Time Zero To Dosing Interval (AUC0-tau)

  Part 1 and Part 2: C1 Day 1, Day 2, Day 15; C2 Day 1; C3 Day 1; - each cycle is 28 days

• All Parts: PK exposure parameter: Area Under The Plasma Concentration-Time Curve From Time Zero To Time With Last Measurable Concentration (AUC0-t)

  Part 1 and Part 2: C1 Day 1, Day 2, Day 15; C2 Day 1; C3 Day 1; - each cycle is 28 days

• All Parts: PK exposure parameter: Area Under The Plasma Concentration-Time Curve From Time Zero To Infinity (AUC0-∞)

  Part 1 and Part 2: C1 Day 1, Day 2, Day 15; C2 Day 1; C3 Day 1; - each cycle is 28 days

Study Arms (1)

STX-241/PFL-241

EXPERIMENTAL

Part 1: Dose Escalation and Backfilling components (Phase Ia) Participants will receive oral (PO) STX-241/PFL-241 twice daily (BID) at fixed doses: 10 mg, 20 mg, 40 mg, 80 mg, 120 mg, 180 mg on a continuous dosing schedule Part 2: Dose Range Optimization (Phase Ib). Participants will receive oral (PO) STX-241/PFL-241 twice daily (BID) at fixed doses selected from Part 1 within the OBD-MTD range for Part 2 on a continuous dosing schedule.

Drug: STX-241

Interventions

STX-241 DRUG

Film-coated tablet Route of administration: Oral

Also known as: PFL-241

STX-241/PFL-241

Eligibility Criteria

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

You may qualify if:

• Signed and dated informed consent for participation in the trial obtained according to International Council for Harmonisation of Technical Requirements of Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP), and national/local regulations.
• Male or female ≥ 18 years of age at the time of signing informed consent.
• Histological confirmation of locally advanced or metastatic, EGFR-mutant (ex19del or L858R mutations) non-small cell lung cancer (NSCLC) Stage IIIB/C or IV (AJCC 8th edition) not eligible for curative intent surgery or chemoradiation.
• Part 1\&2 Disease progression on a 3rd generation EGFR TKI-based therapy (monotherapy or in combination) received at any prior line of treatment.
• Tumor mutation profile:
• Part 1 (backfilling component) and Part 2: Presence of C797X and absence of T790M mutations documented locally (as part of clinical practice) on a sample (blood or tissue) collected after progression on treatment with 3rd generation EGFR TKI.
• Part 1 (Backfilling component), Part 2: At least one measurable target lesion according to RECIST v1.1.
• Eastern cooperative oncology group (ECOG) performance status 0-1.
• Adequate organ function as defined below:
• Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L
• Platelets ≥ 75 x 10\^9/L
• Hemoglobin ≥ 90 g/L.
• Serum total bilirubin ≤ 1.5 x ULN or ≤ 3.0 × ULN for participants with documented Gilbert's syndrome.
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 x ULN. If the participant has liver metastases, AST and ALT ≤5 × ULN.
• Estimated glomerular filtration rate (GFR) ≥ 50 mL/min by CKD-EPI equation

You may not qualify if:

• Participant candidate for targeted therapies available to them (such as but not limited to therapies targeting ALK, BRAF, MET, NTRK, ROS1) as identified by local testing performed after progression to the last line of systemic therapy.
• Participant with rapid progressive disease eligible to receive a platinum-based chemotherapy.
• Participant unable ingest or digest tablets. This can be caused by any impaired gastrointestinal function or disease, such as for example: ulcerative diseases, malabsorption syndrome, small bowel resection, ileus, etc. or any condition causing uncontrolled nausea, vomiting or diarrhea.
• History of a primary malignancy other than NSCLC with the exception of:
• Participants with a previous malignancy that completed all anticancer treatment at least 2 years before signing informed consent and with no evidence of residual disease from the prior malignancy at screening.
• Malignancies with a negligible risk of metastasis or death (i.e. 5-year overall survival rate \> 90%) that are adequately treated - Examples include, but are not limited to, completely resected basal cell carcinoma and squamous cell carcinoma of skin, melanoma in situ, curatively treated prostate cancer, breast cancer and early gastric cancer cured by endoscopic mucosal resection or endoscopic submucosal dissection.
• Spinal cord compression or CNS metastases that are associated with progressive neurological symptoms or require increasing doses of corticosteroids to control the CNS disease. If a participant requires corticosteroids for management of CNS disease, the dose must have been stable for 2 weeks prior to enrollment in the trial.
• History of hypersensitivity to active or inactive ingredients of STX-241, or drugs with a similar chemical structure or from the same class.
• Active, bacterial, fungal, or viral infection, including, but not limited to: Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), and known Human Immunodeficiency Virus (HIV) or Acquired Immunodeficiency Syndrome (AIDS)-related illness, tuberculosis or an infection requiring systemic therapeutic treatment within 2 weeks prior to Day 1 (first administration of STX-241).
• Note: Participants with known HIV infection are permitted if they have controlled infection (undetectable viral load \[HIV ribonucleic acid polymerase chain reaction (PCR)\] and CD4 count \>350 either spontaneously or on a stable antiviral regimen). For participants with controlled HIV infection, monitoring will be performed per local standards.
• Positive SARs-CoV-2 or variants of SARs-CoV2 RT-PCR test or suspected to be infected with SARs-CoV2 or variants of SARsCoV2 with confirmation pending within 2 weeks of first dose of STX-241.
• Impaired cardiovascular function or clinically significant cardiovascular disease (either active or within 6 months prior to signing informed consent), including any of the following:
• Myocardial infarction, acute coronary syndromes including unstable angina, coronary/peripheral artery bypass graft, coronary angioplasty or stenting.
• Symptomatic congestive heart failure (New York Heart Association Classification Class ≥ II).
• Cerebrovascular accident or transient ischemic attack.

Sponsors & Collaborators

• Pierre Fabre Medicament: lead

Study Sites (16)

Sarah Cannon Research Institute (SCRI) (The SCRI Oncology Research Consortium)

Nashville, Tennessee, 37203, United States

RECRUITING

Oncology Consultants (OC) - Texas Medical Center - Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Shanghai East Hospital, Tongji University

Shanghai, 200120, China

RECRUITING

Tianjin Medical University Cancer Institute and Hospital

Tianjin, 300060, China

RECRUITING

Centre Léon Bérard

Lyon, 69008, France

RECRUITING

CHU Hôpital de la Timone

Marseille, 13385, France

RECRUITING

Institut de Cancérologie de l'Ouest (ICO) - René Gauducheau

Saint-Herblain, 44800, France

RECRUITING

Institut Universitaire du Cancer de Toulouse - Oncopole

Toulouse, 31059, France

RECRUITING

Gustave Roussy

Villejuif, 94800, France

RECRUITING

Universitätsklinikum Carl Gustav Carus Dresden

Dresden, 1307, Germany

RECRUITING

Netherlands Cancer Institute

Amsterdam, 1066 CX, Netherlands

RECRUITING

Vall d'Hebron Institut d'Oncologia

Barcelona, 8035, Spain

RECRUITING

Hospital Universitario La Paz

Madrid, 28046, Spain

RECRUITING

Centro Integral Oncológico Clara Campal (CIOCC)

Madrid, 28050, Spain

RECRUITING

National Taiwan University Hospital

Taipei, 10002, Taiwan

RECRUITING

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

RECRUITING

Related Links

• For eligible studies, qualified researchers may request access to individual patient level clinical data. See Pierre Fabre's commitment to transparency of clinical study information Pillar 5.

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Claire A Fabre, MD

CONTACT

+33 6 42 04 84 76; claire.fabre@pierre-fabre.com

Christine Petilaire Bellet

CONTACT

STX241_medical.team@pierre-fabre.com

Study Design

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

Study Record Dates

• First Submitted: August 3, 2024
• First Posted: August 22, 2024
• Study Start: September 17, 2024
• Primary Completion (Estimated): November 20, 2027
• Study Completion (Estimated): July 1, 2030
• Last Updated: September 17, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: This trial data availability is according to the criteria and process described in our website

Locations

TW (2); US (2); NL (1); CN (2); ES (3); FR (5); DE (1)